<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT04502212</url>
  </required_header>
  <id_info>
    <org_study_id>GE Research HUI-01</org_study_id>
    <nct_id>NCT04502212</nct_id>
  </id_info>
  <brief_title>Pilot Study to Assess the Effects of Hepatic Ultrasound Insonification on Subjects With T2DM</brief_title>
  <official_title>An Open-Label, Pilot Study to Assess the Effects of Hepatic Ultrasound Insonification on Glucometabolic Parameters in Subjects With T2DM</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>General Electric Research</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>ProSciento, Inc.</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>General Electric Research</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>Yes</is_fda_regulated_device>
    <is_us_export>Yes</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      This research study is being done to evaluate the effect of hepatic ultrasound insonification&#xD;
      on whole-body insulin sensitivity and evaluate the safety and tolerability of hepatic&#xD;
      ultrasound insonification in subjects with Type 2 Diabetes Mellitus (T2DM).&#xD;
      &quot;Insonify/insonification&quot; is defined as applying to an area or an object carefully-controlled&#xD;
      sound waves, typically as in ultrasound imaging. GE Research is sponsoring this research&#xD;
      study. The purpose of this research study is to:&#xD;
&#xD;
        -  Evaluate the effect of liver ultrasound waves on changes from baseline in whole-body&#xD;
           insulin sensitivity&#xD;
&#xD;
        -  Test the safety and tolerability of liver ultrasound waves in subjects with Type 2&#xD;
           Diabetes Mellitus&#xD;
&#xD;
        -  Evaluate the effect of liver ultrasound waves on change from baseline in glucose&#xD;
           tolerance and insulin secretion&#xD;
&#xD;
        -  Evaluate the effect of liver ultrasound waves on glucose metabolism&#xD;
&#xD;
      Insulin sensitivity refers to how sensitive the body's cells are in response to insulin.&#xD;
&#xD;
      Glucose tolerance refers to the body's ability to handle (tolerate) glucose. Insulin&#xD;
      secretion is a process in which the body releases insulin in response to glucose levels in&#xD;
      the blood becoming elevated.&#xD;
&#xD;
      The study device used in this study is cleared for use by the United States Food and Drug&#xD;
      Administration (FDA) for ultrasound diagnostic exams, however it has not been tested or&#xD;
      approved specifically for modulation of metabolism in people with diabetes. The use of the&#xD;
      study device in this study is investigational and is considered a Non-Significant Risk (NSR).&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This was an open label, exploratory pilot study to assess the effects of hepatic ultrasound&#xD;
      insonification on glucometabolic parameters in subjects with T2DM through selective hepatic&#xD;
      ultrasound of the porta hepatis region of the liver utilizing pulsed ultrasound. The study&#xD;
      was to consist of 1 cohort comprising up to 15 subjects. Dropouts and withdrawals could have&#xD;
      been replaced until the anticipated number of subjects completed the study. Finally, the&#xD;
      study consisted of one cohort with 36 subjects enrolled, including 20 screen failures, 15&#xD;
      subjects that completed the study (1 completer had an incorrect infusion parameter and was&#xD;
      removed from clamp analysis), and 1 subject that was discontinued at the discretion of the&#xD;
      Investigator. As this was an exploratory, open-label study, no randomization or blinding was&#xD;
      performed and no-unblinding codes were required.&#xD;
&#xD;
      The study included a Screening Period, Observational Period 1, 3 consecutive days of hepatic&#xD;
      ultrasound insonification, and Observational Period 2. Each Observational Period was divided&#xD;
      into an In-house Period and an Outpatient Visit (OPV). The Screening Period was performed up&#xD;
      to 28 days prior to the first In-house Period. For eligible subjects with a body mass index&#xD;
      (BMI) &gt; 35.0 and ≤ 40.0 kg/m2 and/or a waist circumference &gt; 40 and ≤ 45 inches, an&#xD;
      ultrasound examination was added to confirm eligibility, and the Screening Period was&#xD;
      extended to at least 30 days. The first Observational Period lasted approximately 2-weeks&#xD;
      (Days -1 to 14). On the morning of Day -1, subjects checked into the clinic for a 3-day&#xD;
      In-house Period; subjects may have been released from the clinic on Day 2. Subjects were&#xD;
      contacted via telephone every other day until the next In-house Period. On Day 8, subjects&#xD;
      checked into the clinic for an OPV. On Day 15, subjects checked into the clinic in fasting&#xD;
      conditions for a 4-day In-house Period. Insonifications were performed on three consecutive&#xD;
      days (Days 15, 16 and 17). Subjects may have been released from the clinic on Day 18. The&#xD;
      second Observational Period lasted 11 days (Days 18 to 28). Subjects were contacted via&#xD;
      telephone every other day until the Follow-up Visit. On Day 22, subjects checked into the&#xD;
      clinic for the OPV. The Follow-up Visit was performed on Day 28.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">July 30, 2020</start_date>
  <completion_date type="Actual">May 24, 2021</completion_date>
  <primary_completion_date type="Actual">May 24, 2021</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Other</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Change From Baseline in Glucose Disposal Rate: Insulin Ratio During Steady State (M/I)</measure>
    <time_frame>Day 2 (Baseline) to Day 17</time_frame>
    <description>To evaluate the effect of hepatic ultrasound insonification on changes from baseline in whole-body insulin sensitivity during a two-step hyperinsulinemic, euglycemic clamp with stable isotope labeled glucose tracer</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change From Baseline in Endogenous Glucose Production (EGP)</measure>
    <time_frame>Day 2 (Baseline) to Day 17</time_frame>
    <description>To evaluate the effect of hepatic ultrasound insonification on changes from baseline in whole-body insulin sensitivity during a two-step hyperinsulinemic, euglycemic clamp with stable isotope labeled glucose tracer</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change From Baseline in Insulin-Mediated EGP Suppression During the Clamp Timepoint With Low Rate Insulin Infusion (Step 1)</measure>
    <time_frame>Day 2 (Baseline) to Day 17</time_frame>
    <description>To evaluate the effect of hepatic ultrasound insonification on changes from baseline in whole-body insulin sensitivity during a two-step hyperinsulinemic, euglycemic clamp with stable isotope labeled glucose tracer&#xD;
For each clamp, the degree of EGP suppression from the fasting EGP value was to be determined during the last 30 minutes point during each step of the two-step H-E clamp using the following equation:&#xD;
% EGP suppression = 1 - (EGP clamp/EGP fasting) Partial suppression of EGP during Step 1 was to be assessed to determine hepatic insulin sensitivity and EGP suppression during Step 2 was to be measured to confirm that EGP was (near) fully suppressed to allow the determination of extrahepatic insulin sensitivity.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change From Baseline in Rate of Glucose Disappearance (Rd)</measure>
    <time_frame>Day 2 (Baseline) to Day 17</time_frame>
    <description>To evaluate the effect of hepatic ultrasound insonification on changes from baseline in whole-body insulin sensitivity during a two-step hyperinsulinemic, euglycemic clamp with stable isotope labeled glucose tracer</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Incidence of Adverse Device Effects (ADEs) With a Severity Score of 1: Treatment Emergent Adverse Events (TEAEs) by System Organ Class and Preferred Term</measure>
    <time_frame>Screening to Day 28</time_frame>
    <description>To evaluate safety and tolerability of hepatic ultrasound insonification in subjects with T2DM. Incidence of adverse device effects included observations of Incidence and severity of clinically significant laboratory abnormalities, Change from baseline in vital signs (blood pressure, temperature, respiratory rate, and heart rate), Incidence and severity of clinical findings on physical examination, Change from baseline in 12-lead electrocardiogram (ECG) parameters; the primary ECG endpoint was QTcF.&#xD;
To evaluate safety and tolerability of hepatic ultrasound insonification in subjects with T2DM: [Severity Score: 1=Mild; 2=Moderate; 3=Severe; 4=Life-Threatening; 5=Death]</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incidence of Clinically Significant Laboratory Abnormalities</measure>
    <time_frame>Screening to Day 28</time_frame>
    <description>To evaluate safety and tolerability of hepatic ultrasound insonification in subjects with T2DM</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incidence of Significant Clinical Findings on Physical Examination</measure>
    <time_frame>Screening to Day 28</time_frame>
    <description>To evaluate safety and tolerability of hepatic ultrasound insonification in subjects with T2DM</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in Vital Signs: Blood Pressure</measure>
    <time_frame>Baseline to Day 28 - Baseline was defined as the last non-missing value collected prior to the first on study hepatic ultrasound insonification</time_frame>
    <description>To evaluate safety and tolerability of hepatic ultrasound insonification in subjects with T2DM</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in Vital Signs: Pulse Rate</measure>
    <time_frame>Baseline to Day 28 - Baseline was defined as the last non-missing value collected prior to the first on study hepatic ultrasound insonification</time_frame>
    <description>To evaluate safety and tolerability of hepatic ultrasound insonification in subjects with T2DM</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in Vital Signs: Respiratory Rate</measure>
    <time_frame>Baseline to Day 28 - Baseline was defined as the last non-missing value collected prior to the first on study hepatic ultrasound insonification</time_frame>
    <description>To evaluate safety and tolerability of hepatic ultrasound insonification in subjects with T2DM</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in Vital Signs: Temperature</measure>
    <time_frame>Baseline to Day 28 - Baseline was defined as the last non-missing value collected prior to the first on study hepatic ultrasound insonification</time_frame>
    <description>To evaluate safety and tolerability of hepatic ultrasound insonification in subjects with T2DM</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incidence of Clinically Significant Changes in Vital Sign Values</measure>
    <time_frame>Screening to Day 28</time_frame>
    <description>To evaluate safety and tolerability of hepatic ultrasound insonification in subjects with T2DM</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in 12-lead Electrocardiogram (ECG) Parameters</measure>
    <time_frame>Baseline to Day 28 - Baseline was defined as the last non-missing value collected prior to the first on study hepatic ultrasound insonification</time_frame>
    <description>To evaluate safety and tolerability of hepatic ultrasound insonification in subjects with T2DM</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incidence of Clinically Significant Changes in ECG Measurements</measure>
    <time_frame>Screening to Day 28</time_frame>
    <description>To evaluate safety and tolerability of hepatic ultrasound insonification in subjects with T2DM</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in Insulin Sensitivity Index (SI)</measure>
    <time_frame>Day 2 (Baseline) to Day 17</time_frame>
    <description>To evaluate the effect of hepatic ultrasound insonification on changes from baseline in whole-body insulin sensitivity during a two-step hyperinsulinemic, euglycemic clamp with stable isotope labeled glucose tracer.&#xD;
The Insulin Sensitivity Index was to be calculated from the H-E clamp data using the formula included in the SAP, with Step 1 indicating the first phase of the clamp, or the period of administration of the first (lower) insulin infusion rate and Step 2 indicating the second phase of the clamp or the period of administration of the second (higher) insulin infusion rate. Mean GIRs and mean plasma insulin concentrations were to be calculated during steady state for the applicable step(s).&#xD;
Change from baseline of SI was then to be computed for each subject as:&#xD;
Change from baseline (SI) = SI2 - SI1, where Clamp 2 was the second clamp and Clamp 1 was the first clamp (completed on Day 2, prior to first insonification).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in Glucose Disposal Rate During Steady State (M)</measure>
    <time_frame>Day 2 (Baseline) to Day 17</time_frame>
    <description>To evaluate the effect of hepatic ultrasound insonification on changes from baseline in whole-body insulin sensitivity during a two-step hyperinsulinemic, euglycemic clamp with stable isotope labeled glucose tracer</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in Glucose Metabolic Clearance Rate During Steady State (MCR)</measure>
    <time_frame>Day 2 (Baseline) to Day 17</time_frame>
    <description>To evaluate the effect of hepatic ultrasound insonification on changes from baseline in whole-body insulin sensitivity during a two-step hyperinsulinemic, euglycemic clamp with stable isotope labeled glucose tracer</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in Homeostasis Model Assessment of Insulin Resistance (HOMA2-IR)</measure>
    <time_frame>Day 15 (Baseline) to Day 18</time_frame>
    <description>To evaluate the effect of hepatic ultrasound insonification on glucose metabolism parameters, assessed by a Homeostasis Model. A higher value denotes an increased level of insulin resistance, and a lower value denotes an decreased level of insulin resistance. The value is computed based on fasting insulin and glucose values.&#xD;
The HOMA2 results were produced by the HOMA2 calculator with FPG and insulin concentration obtained from safety laboratory assessments as the inputs to the calculator at https://www.dtu.ox.ac.uk/homacalculator/. Please see citation (see references module): &quot;Levy 1998 Levy JC, Matthews DR, &amp; Hermans MP. (1998). Correct homeostasis model assessment (HOMA) evaluation uses the computer program. Diabetes Care. 21:2191-2192.&quot;</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in Homeostasis Model Assessment of Insulin Secretion (HOMA2-B)</measure>
    <time_frame>Day 15 (Baseline) to Day 18</time_frame>
    <description>To evaluate the effect of hepatic ultrasound insonification on glucose metabolism parameters, assessed by a Homeostasis Model. The HOMA2 results were to be produced by the HOMA2 calculator with FPG and insulin concentration obtained from safety laboratory assessments as the inputs to the calculator at https://www.dtu.ox.ac.uk/homacalculator/. HOMA2-B values estimate steady state pancreatic beta cell function, as a percent of a normal reference population. See citation: &quot;Levy JC, Matthews DR, &amp; Hermans MP. (1998). Correct homeostasis model assessment (HOMA) evaluation uses the computer program. Diabetes Care. 21:2191-2192.&quot;</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in Fasting Plasma Glucose (FPG)</measure>
    <time_frame>Baseline to Day 18 - Baseline was defined as the last non-missing value collected prior to the first on study hepatic ultrasound insonification</time_frame>
    <description>To evaluate the effect of hepatic ultrasound insonification on glucose metabolism parameters, assessed by fasting plasma glucose blood test</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in Oral Glucose Tolerance Test (OGTT) Area Under the Curve (AUC 0-180): Glucose</measure>
    <time_frame>Day 1 (Baseline) to Day 16</time_frame>
    <description>To evaluate the effect of hepatic ultrasound insonification on change from baseline in glucose tolerance and insulin secretion, assessed by an oral glucose tolerance test (OGTT). AUC in this outcome is calculated using the absolute value of glucose measures (compared to incremental AUC below which uses baseline (time 0 glucose) subtracted values).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in Oral Glucose Tolerance Test (OGTT) Area Under the Curve (AUC 0-180): Insulin</measure>
    <time_frame>Day 1 (Baseline) to Day 16</time_frame>
    <description>To evaluate the effect of hepatic ultrasound insonification on change from baseline in glucose tolerance and insulin secretion, assessed by an oral glucose tolerance test (OGTT). AUC in this outcome is calculated using the absolute value of insulin measures (compared to incremental AUC below which uses baseline (time 0 insulin) subtracted values).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in Continuous Glucose Monitoring System (CGMS): Time in Ranges</measure>
    <time_frame>14:00 on Day -1 to 22:00 on Day 1 (Baseline) to 14:00 on Day 15 to 22:00 on Day 16 - omitting data collected between a subject's OGTT glucose consumption start time + 180 minutes</time_frame>
    <description>To evaluate the effect of hepatic ultrasound insonification on glucose metabolism parameters, assessed by a continuous glucose monitoring system (CGMS)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in Continuous Glucose Monitoring System (CGMS): Average Daily Glucose</measure>
    <time_frame>14:00 on Day -1 to 22:00 on Day 1 (Baseline) to 14:00 on Day 15 to 22:00 on Day 16 - omitting data collected between a subject's OGTT glucose consumption start time + 180 minutes</time_frame>
    <description>To evaluate the effect of hepatic ultrasound insonification on glucose metabolism parameters, assessed by a continuous glucose monitoring system (CGMS)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in Continuous Glucose Monitoring System (CGMS): Blood Glucose Coefficient of Variation</measure>
    <time_frame>14:00 on Day -1 to 22:00 on Day 1 (Baseline) to 14:00 on Day 15 to 22:00 on Day 16 - omitting data collected between a subject's OGTT glucose consumption start time + 180 minutes</time_frame>
    <description>To evaluate the effect of hepatic ultrasound insonification on glucose metabolism parameters, assessed by a continuous glucose monitoring system (CGMS)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in Continuous Glucose Monitoring System (CGMS): Low/High Blood Glucose Index</measure>
    <time_frame>14:00 on Day -1 to 22:00 on Day 1 (Baseline) to 14:00 on Day 15 to 22:00 on Day 16 - omitting data collected between a subject's OGTT glucose consumption start time + 180 minutes</time_frame>
    <description>To evaluate the effect of hepatic ultrasound insonification on glucose metabolism parameters, assessed by a continuous glucose monitoring system (CGMS)&#xD;
To calculate the LBGI and HBGI, the original BG data for each day/period was to be transformed such that it was centered by zero and bound between -sqrt(10) and sqrt(10).&#xD;
f(BG,α,β) = [(ln(BG))1.084 - 5.381]*1.509&#xD;
The transformed values were then to be input into the BG risk function:&#xD;
r(BG) = 10 * f(BG,α,β)2&#xD;
The risk of each observation was further to be transformed into two series, risk of low BG series, rl(BG), and risk of high BG series, rh(BG):&#xD;
rl(BG) = r(BG) if f(BG) &lt; 0 and 0 otherwise rh(BG) = r(BG) if f(BG) &gt; 0 and 0 otherwise These series were then to be averaged to produce the LBGI and the HBGI as shown in the equations in the SAP.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incidence of Adverse Device Effects (ADEs) With a Severity Score of 2: Treatment Emergent Adverse Events (TEAEs) by System Organ Class and Preferred Term</measure>
    <time_frame>Screening to Day 28</time_frame>
    <description>To evaluate safety and tolerability of hepatic ultrasound insonification in subjects with T2DM. Incidence of adverse device effects included observations of Incidence and severity of clinically significant laboratory abnormalities, Change from baseline in vital signs (blood pressure, temperature, respiratory rate, and heart rate), Incidence and severity of clinical findings on physical examination, Change from baseline in 12-lead electrocardiogram (ECG) parameters; the primary ECG endpoint was QTcF.&#xD;
To evaluate safety and tolerability of hepatic ultrasound insonification in subjects with T2DM: [Severity Score: 1=Mild; 2=Moderate; 3=Severe; 4=Life-Threatening; 5=Death]</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incidence of Adverse Device Effects (ADEs) With a Severity Score of 3: Treatment Emergent Adverse Events (TEAEs) by System Organ Class and Preferred Term</measure>
    <time_frame>Screening to Day 28</time_frame>
    <description>To evaluate safety and tolerability of hepatic ultrasound insonification in subjects with T2DM. Incidence of adverse device effects included observations of Incidence and severity of clinically significant laboratory abnormalities, Change from baseline in vital signs (blood pressure, temperature, respiratory rate, and heart rate), Incidence and severity of clinical findings on physical examination, Change from baseline in 12-lead electrocardiogram (ECG) parameters; the primary ECG endpoint was QTcF.&#xD;
To evaluate safety and tolerability of hepatic ultrasound insonification in subjects with T2DM: [Severity Score: 1=Mild; 2=Moderate; 3=Severe; 4=Life-Threatening; 5=Death]</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incidence of Adverse Device Effects (ADEs) With a Severity Score of 4: Treatment Emergent Adverse Events (TEAEs) by System Organ Class and Preferred Term</measure>
    <time_frame>Screening to Day 28</time_frame>
    <description>To evaluate safety and tolerability of hepatic ultrasound insonification in subjects with T2DM. Incidence of adverse device effects included observations of Incidence and severity of clinically significant laboratory abnormalities, Change from baseline in vital signs (blood pressure, temperature, respiratory rate, and heart rate), Incidence and severity of clinical findings on physical examination, Change from baseline in 12-lead electrocardiogram (ECG) parameters; the primary ECG endpoint was QTcF.&#xD;
To evaluate safety and tolerability of hepatic ultrasound insonification in subjects with T2DM: [Severity Score: 1=Mild; 2=Moderate; 3=Severe; 4=Life-Threatening; 5=Death]</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incidence of Adverse Device Effects (ADEs) With a Severity Score of 5: Treatment Emergent Adverse Events (TEAEs) by System Organ Class and Preferred Term</measure>
    <time_frame>Screening to Day 28</time_frame>
    <description>To evaluate safety and tolerability of hepatic ultrasound insonification in subjects with T2DM. Incidence of adverse device effects included observations of Incidence and severity of clinically significant laboratory abnormalities, Change from baseline in vital signs (blood pressure, temperature, respiratory rate, and heart rate), Incidence and severity of clinical findings on physical examination, Change from baseline in 12-lead electrocardiogram (ECG) parameters; the primary ECG endpoint was QTcF.&#xD;
To evaluate safety and tolerability of hepatic ultrasound insonification in subjects with T2DM: [Severity Score: 1=Mild; 2=Moderate; 3=Severe; 4=Life-Threatening; 5=Death]</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Change From Baseline in Exploratory Biomarkers</measure>
    <time_frame>Baseline to Day 18 - Baseline was defined as the last non-missing value collected prior to the first on study hepatic ultrasound insonification</time_frame>
    <description>To evaluate the effect of hepatic ultrasound insonification on glucose metabolism parameters, as assessed by exploratory markers in blood samples</description>
  </other_outcome>
  <other_outcome>
    <measure>Change From Baseline in Long-term Glucose Parameters: Fructosamine</measure>
    <time_frame>Baseline to Day 18 - Baseline was defined as the last non-missing value collected prior to the first on study hepatic ultrasound insonification</time_frame>
    <description>To evaluate the effect of hepatic ultrasound insonification on glucose metabolism parameters, as assessed by long-term glucose markers in blood samples</description>
  </other_outcome>
  <other_outcome>
    <measure>Change From Baseline in Long-term Glucose Parameters: Hemoglobin A1C</measure>
    <time_frame>Baseline to Day 18 - Baseline was defined as the last non-missing value collected prior to the first on study hepatic ultrasound insonification</time_frame>
    <description>To evaluate the effect of hepatic ultrasound insonification on glucose metabolism parameters, as assessed by long-term glucose markers in blood samples</description>
  </other_outcome>
  <other_outcome>
    <measure>Change From Baseline in Lipid Metabolism Parameters: Cholesterol and Triglycerides</measure>
    <time_frame>Baseline to Day 18 - Baseline was defined as the last non-missing value collected prior to the first on study hepatic ultrasound insonification</time_frame>
    <description>To evaluate the effect of hepatic ultrasound insonification on glucose metabolism parameters, as assessed by lipid metabolism markers in blood samples</description>
  </other_outcome>
  <other_outcome>
    <measure>Change From Baseline in Lipid Metabolism Parameters: Free Fatty Acids</measure>
    <time_frame>Baseline to Day 18 - Baseline was defined as the last non-missing value collected prior to the first on study hepatic ultrasound insonification</time_frame>
    <description>To evaluate the effect of hepatic ultrasound insonification on glucose metabolism parameters, as assessed by lipid metabolism markers in blood samples</description>
  </other_outcome>
  <other_outcome>
    <measure>Change From Baseline in Inflammatory Biomarkers: Adiponectin</measure>
    <time_frame>Baseline to Day 18 - Baseline was defined as the last non-missing value collected prior to the first on study hepatic ultrasound insonification</time_frame>
    <description>To evaluate the effect of hepatic ultrasound insonification on glucose metabolism parameters, as assessed by inflammatory biomarkers in blood samples</description>
  </other_outcome>
  <other_outcome>
    <measure>Change From Baseline in Inflammatory Biomarkers: C Reactive Protein</measure>
    <time_frame>Baseline to Day 18 - Baseline was defined as the last non-missing value collected prior to the first on study hepatic ultrasound insonification</time_frame>
    <description>To evaluate the effect of hepatic ultrasound insonification on glucose metabolism parameters, as assessed by inflammatory biomarkers in blood samples</description>
  </other_outcome>
  <other_outcome>
    <measure>Change From Baseline in Inflammatory Biomarkers: Interleukin-6</measure>
    <time_frame>Baseline to Day 18 - Baseline was defined as the last non-missing value collected prior to the first on study hepatic ultrasound insonification</time_frame>
    <description>To evaluate the effect of hepatic ultrasound insonification on glucose metabolism parameters, as assessed by inflammatory biomarkers in blood samples</description>
  </other_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">16</enrollment>
  <condition>Type 2 Diabetes</condition>
  <arm_group>
    <arm_group_label>Insonification</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>All subjects enrolled will receive a 3-day, 15 minute per day ultrasound insonification targeting the portis hepatis (liver).</description>
  </arm_group>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>Hepatic Ultrasound Insonification</intervention_name>
    <description>Hepatic ultrasound insonification will be performed after an overnight fast (no food or drinks except for water for at least 10 hours) at approximately the same time on each day for three days.</description>
    <arm_group_label>Insonification</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Male or female subjects with type 2 diabetes ≥ 12 months.&#xD;
&#xD;
          2. Age ≥ 21 and ≤ 75 years.&#xD;
&#xD;
          3. Stable treatment with diet and exercise or stable treatment with metformin&#xD;
             monotherapy. Stable treatment is defined as no change in treatment during the last 3&#xD;
             months.&#xD;
&#xD;
          4. HbA1c &gt; 6.5% and&lt; 10% by local laboratory analysis (one retest is permitted with the&#xD;
             result of the last test being conclusive).&#xD;
&#xD;
          5. Body Mass Index (BMI) ≥ 18 to ≤ 35.0 kg/m2.&#xD;
&#xD;
          6. Waist circumference ≤ 40 inches (≤ 102 cm).&#xD;
&#xD;
          7. Considered generally healthy upon completion of medical history, physical examination&#xD;
             and biochemical investigations as judged by the Principal Investigator.&#xD;
&#xD;
          8. Female subjects must be non-pregnant and non-lactating and have a negative serum&#xD;
             pregnancy test at Screening. Females may be surgically sterile, postmenopausal or of&#xD;
             child-bearing potential. Females of childbearing potential must be using an acceptable&#xD;
             method of birth control.&#xD;
&#xD;
          9. Ability to provide written informed consent.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. History or current diagnosis with T1DM or T2DM subjects on insulin or other injectable&#xD;
             therapies not allowed for this study (as listed in table of Prohibited Medication&#xD;
             below).&#xD;
&#xD;
          2. A subject who is already indicated for medication escalation of their current diabetic&#xD;
             therapy, or, who based upon study entry criteria, would be indicated for medication&#xD;
             escalation during the course of the study (as assessed by the qualified Principal&#xD;
             Investigator).&#xD;
&#xD;
          3. A subject who has diabetic complications, i.e., acute proliferative retinopathy or&#xD;
             maculopathy, severe gastroparesis, and/or severe neuropathy, in particular autonomic&#xD;
             neuropathy, as judged by the Principal Investigator.&#xD;
&#xD;
          4. Recurrent severe hypoglycemia (more than 1 event ≤ 6 month) or hypoglycemic&#xD;
             unawareness or recent severe ketoacidosis (hospitalization ≤ 6 month), as judged by&#xD;
             the Principal Investigator.&#xD;
&#xD;
          5. Persistent systolic blood pressure &gt; 150 mm Hg and/or diastolic blood pressure &gt; 95 mm&#xD;
             Hg at screening. (Subjects may be re-checked once on the same day).&#xD;
&#xD;
          6. Treatment with antihypertensive medication is not allowed, unless antihypertensive&#xD;
             medication is given on a stable dose for at least 2 months prior to screening.&#xD;
&#xD;
          7. Subjects with a clinically significant history or active disease of any of the&#xD;
             following body systems: pulmonary, neurological (including dementia, neurodegenerative&#xD;
             disease, movement disorder, spinal disorders), pancreatic (including pancreatitis),&#xD;
             immunological or systemic inflammatory (including systemic lupus erythematosus [SLE],&#xD;
             rheumatoid arthritis [RA]), dermatological, endocrine, genitourinary or hematological&#xD;
             (including sickle cell anemia or other anemia syndromes, monocytosis,&#xD;
             thrombocytopenia).&#xD;
&#xD;
          8. Subjects with a history or clinically active malignancy (history of basal cell&#xD;
             carcinoma [BCC] is allowed).&#xD;
&#xD;
          9. History or current diagnosis of cardiac dysrhythmias or heart disease, defined as&#xD;
             symptomatic heart failure (New York Heart Association class III or IV), myocardial&#xD;
             infarction, unstable angina requiring medication.&#xD;
&#xD;
         10. Transient ischemic attack [TIA], cerebral infarct, or cerebral hemorrhage.&#xD;
&#xD;
         11. Invasive cardiovascular procedure, such as coronary artery bypass graft surgery&#xD;
             (CABG), or angioplasty/percutaneous coronary intervention (PCI) within 6 months of&#xD;
             screening.&#xD;
&#xD;
         12. PHistory of or presence of clinically significant ECG findings (e.g., QTcF &gt; 450 msec&#xD;
             for males, QTcF &gt; 470 msec for females, LBBB) at Screening, or cardiac arrhythmia&#xD;
             requiring medical or surgical treatment within 6 months prior to screening.&#xD;
&#xD;
         13. History of renal disease or abnormal kidney function tests at Screening (glomerular&#xD;
             filtration rate [GFR] &lt; 60 mL/min/1.73m2 as estimated using the MDRD equation).&#xD;
&#xD;
         14. History or clinically significant active hepatic disease or clinically significant&#xD;
             abnormal hepatic function tests at Screening suggestive of hepatic impairment (e.g.,&#xD;
             ALT and/or AST &gt;2 x ULN), total bilirubin &gt; 1 x ULN).&#xD;
&#xD;
         15. Subjects with a history or presence of any psychiatric disorder that, in the opinion&#xD;
             of the Principal Investigator, might confound the results of the trial or pose&#xD;
             additional risk in administering the investigational product to the subject.&#xD;
&#xD;
         16. Personal or family history of hypercoagulability or thromboembolic disease, including&#xD;
             deep vein thrombosis and/or pulmonary embolism (PE)&#xD;
&#xD;
         17. History of surgical treatment for obesity (bariatric surgery, gastric banding, etc.)&#xD;
             or any other gastrointestinal surgery (including appendectomy, cholecystectomy), any&#xD;
             malabsorption disorder, severe gastroparesis, any GI procedure for weight loss&#xD;
             (including LAP-BAND®), as well as clinically significant gastrointestinal disorders&#xD;
             (e.g. peptic ulcers, severe GERD) at Screening.&#xD;
&#xD;
         18. History of any major surgery within 3 months prior to screening.&#xD;
&#xD;
         19. Any nerve stimulation study or implanted stimulator, including previously or currently&#xD;
             implanted vagus nerve stimulator, previously or currently implanted spinal cord&#xD;
             stimulator, other implanted electronic medical device, such as implanted pacemaker or&#xD;
             cardioverter/defibrillator (AICD) or history of seizures.&#xD;
&#xD;
         20. Diagnosis of sleep apnea.&#xD;
&#xD;
         21. Participation in an investigational study within 30 days of screening or 5 half-lives&#xD;
             within the last dose of any investigational product given during the investigational&#xD;
             study, whichever is longer.&#xD;
&#xD;
         22. Current use of any drugs (other than current treatment for diabetes mellitus) that are&#xD;
             known to interfere with glucose or insulin metabolism as stated below in table&#xD;
             prohibited medication.&#xD;
&#xD;
         23. Thyroid hormone use is not allowed unless medication is given on a stable dose for at&#xD;
             least 3 months prior to screening.&#xD;
&#xD;
         24. Chronic use of acetaminophen, and inability to wash-out and abstain from use during&#xD;
             the study, as it would interfere with the CGMS assessment.&#xD;
&#xD;
         25. Subject is unable to tolerate adhesive tape or has any unresolved adverse skin&#xD;
             reaction in the area of the sensor placement.&#xD;
&#xD;
         26. Implanted pacemaker or cardioverter/defibrillator (AICD).&#xD;
&#xD;
         27. Daily use of more than 5 cigarettes/day or equivalent use of any tobacco- or&#xD;
             nicotine-containing product (such as, but not limited to vaping, transdermal nicotine&#xD;
             patch, nicotine gum use, etc.) within 4 weeks prior to screening. Subjects must be&#xD;
             able to abstain from any tobacco or nicotine containing products during confinement&#xD;
             period.&#xD;
&#xD;
         28. Any use of marijuana within 4 weeks prior to screening and positive test at screening.&#xD;
&#xD;
         29. History of any active infection, except mild viral disease, such as common cold,&#xD;
             within 30 days prior to screening.&#xD;
&#xD;
         30. History of any recent traumatic injury, including intracerebral hemorrhage and&#xD;
             visceral injury.&#xD;
&#xD;
         31. History of alcohol or illicit drug abuse as judged by the Principal Investigator&#xD;
             within past 12 months or positive test at screening. Any use of alcohol within 4 days&#xD;
             prior to baseline assessment. Subjects must be able to abstain from any alcohol during&#xD;
             confinement period.&#xD;
&#xD;
         32. Known history or positive test for hepatitis B surface antigen (HBsAg), hepatitis C&#xD;
             antibody (HCV Ab), human immunodeficiency virus type 1 (HIV-1) or type 2 (HIV-2)&#xD;
&#xD;
         33. Donation or loss of &gt; 500 mL of blood or blood product within 56 days prior to&#xD;
             screening&#xD;
&#xD;
         34. Mental incapacity, unwillingness or language barriers precluding adequate&#xD;
             understanding and to follow verbal commands during the ultrasound session or&#xD;
             cooperation.&#xD;
&#xD;
         35. An abdominal ultrasound scan or exam within 1 month prior to screening and/or any&#xD;
             pre-planned ultrasound examinations during the study, or the need to participate in&#xD;
             any unplanned outside ultrasound procedures during study.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>21 Years</minimum_age>
    <maximum_age>75 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Bridgette Boggess Franey, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>ProSciento, Inc.</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>ProSciento</name>
      <address>
        <city>Chula Vista</city>
        <state>California</state>
        <zip>91911</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <link>
    <url>https://www.dtu.ox.ac.uk/homacalculator/</url>
    <description>Related Info</description>
  </link>
  <reference>
    <citation>Levy JC, Matthews DR, Hermans MP. Correct homeostasis model assessment (HOMA) evaluation uses the computer program. Diabetes Care. 1998 Dec;21(12):2191-2. doi: 10.2337/diacare.21.12.2191. No abstract available.</citation>
    <PMID>9839117</PMID>
  </reference>
  <verification_date>March 2022</verification_date>
  <study_first_submitted>July 29, 2020</study_first_submitted>
  <study_first_submitted_qc>August 3, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">August 6, 2020</study_first_posted>
  <results_first_submitted>November 4, 2021</results_first_submitted>
  <results_first_submitted_qc>May 9, 2022</results_first_submitted_qc>
  <results_first_posted type="Actual">June 2, 2022</results_first_posted>
  <last_update_submitted>May 9, 2022</last_update_submitted>
  <last_update_submitted_qc>May 9, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">June 2, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>No</document_has_sap>
      <document_date>September 24, 2020</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/12/NCT04502212/Prot_000.pdf</document_url>
    </provided_document>
    <provided_document>
      <document_type>Statistical Analysis Plan</document_type>
      <document_has_protocol>No</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>June 30, 2021</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/12/NCT04502212/SAP_001.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <recruitment_details>Of the 36 subjects enrolled into the screening visit, 16 subjects were enrolled into the study and 14 subjects completed the study for all outcomes. Of the 16 subjects enrolled, 1 subject discontinued the study at the discretion of the Investigator and 1 subject failed to complete only the clamp outcomes (i.e. completed all non-clamp outcomes) due to a clamp protocol deviation.&#xD;
Of the 16 subjects enrolled, 3 subjects failed the initial screen and were rescreened at a later date.</recruitment_details>
      <group_list>
        <group group_id="P1">
          <title>Ultrasound Insonification Effect Population</title>
          <description>The Ultrasound Insonification Effect Population was to consist of all subjects who received at least 1 hepatic ultrasound insonification and included 14 subjects.&#xD;
The Safety Population was to consist of all subjects who received at least 1 hepatic ultrasound insonification and included 16 subjects.&#xD;
One subject had unevaluable data and was excluded from the Ultrasound Insonification Effect Population; however, the subject was included in the Safety Population.&#xD;
One subject had Step 1 of the Day 17 clamp extended by 60 minutes, per PI discretion, following a protocol deviation and was excluded from the Ultrasound Insonification Effect Population; however, the subject was included in the Safety Population.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="16"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="14"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="2"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Unevaluable data; excluded from Ultrasound Insonification Effect Pop; included in Safety Pop</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Clamp protocol deviation; excluded from Ultrasound Insonification Effect Pop; included in Safety Pop</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <population>Demographic characteristics by subject for all enrolled subjects.</population>
      <group_list>
        <group group_id="B1">
          <title>Ultrasound Insonification Effect Population</title>
          <description>The Ultrasound Insonification Effect Population was to consist of all subjects who received at least 1 hepatic ultrasound insonification and completed the study for all outcomes (without being discontinued from the study at the discretion of the Investigator or failing to complete the clamp outcomes due to protocol deviation) and included 14 subjects.&#xD;
The Safety Population was to consist of all subjects who received at least 1 hepatic ultrasound insonification and included 16 subjects.</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="16"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="61.9" spread="5.39"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="5"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="11"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Ethnicity (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="10"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="6"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>American Indian or Alaska Native</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="12"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Change From Baseline in Glucose Disposal Rate: Insulin Ratio During Steady State (M/I)</title>
        <description>To evaluate the effect of hepatic ultrasound insonification on changes from baseline in whole-body insulin sensitivity during a two-step hyperinsulinemic, euglycemic clamp with stable isotope labeled glucose tracer</description>
        <time_frame>Day 2 (Baseline) to Day 17</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Ultrasound Insonification Effect Population</title>
            <description>The Ultrasound Insonification Effect Population was to consist of all subjects who received at least 1 hepatic ultrasound insonification and included 14 subjects.&#xD;
The Safety Population was to consist of all subjects who received at least 1 hepatic ultrasound insonification and included 16 subjects.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in Glucose Disposal Rate: Insulin Ratio During Steady State (M/I)</title>
          <description>To evaluate the effect of hepatic ultrasound insonification on changes from baseline in whole-body insulin sensitivity during a two-step hyperinsulinemic, euglycemic clamp with stable isotope labeled glucose tracer</description>
          <units>mg/kg/min per microU/ml</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="14"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Clamp Timepoint with Low Rate Insulin Infusion (Step 1)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.055" spread="0.0932"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Clamp Timepoint with High Rate Insulin Infusion (Step 2)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.004" spread="0.0161"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Change From Baseline in Endogenous Glucose Production (EGP)</title>
        <description>To evaluate the effect of hepatic ultrasound insonification on changes from baseline in whole-body insulin sensitivity during a two-step hyperinsulinemic, euglycemic clamp with stable isotope labeled glucose tracer</description>
        <time_frame>Day 2 (Baseline) to Day 17</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Ultrasound Insonification Effect Population</title>
            <description>The Ultrasound Insonification Effect Population was to consist of all subjects who received at least 1 hepatic ultrasound insonification and included 14 subjects.&#xD;
The Safety Population was to consist of all subjects who received at least 1 hepatic ultrasound insonification and included 16 subjects.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in Endogenous Glucose Production (EGP)</title>
          <description>To evaluate the effect of hepatic ultrasound insonification on changes from baseline in whole-body insulin sensitivity during a two-step hyperinsulinemic, euglycemic clamp with stable isotope labeled glucose tracer</description>
          <units>mg/kg/min</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="14"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Clamp Timepoint prior to Insulin Infusion (Fasting)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.004" spread="0.2316"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Clamp Timepoint with Low Rate Insulin Infusion (Step 1)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.169" spread="0.4849"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Change From Baseline in Insulin-Mediated EGP Suppression During the Clamp Timepoint With Low Rate Insulin Infusion (Step 1)</title>
        <description>To evaluate the effect of hepatic ultrasound insonification on changes from baseline in whole-body insulin sensitivity during a two-step hyperinsulinemic, euglycemic clamp with stable isotope labeled glucose tracer&#xD;
For each clamp, the degree of EGP suppression from the fasting EGP value was to be determined during the last 30 minutes point during each step of the two-step H-E clamp using the following equation:&#xD;
% EGP suppression = 1 - (EGP clamp/EGP fasting) Partial suppression of EGP during Step 1 was to be assessed to determine hepatic insulin sensitivity and EGP suppression during Step 2 was to be measured to confirm that EGP was (near) fully suppressed to allow the determination of extrahepatic insulin sensitivity.</description>
        <time_frame>Day 2 (Baseline) to Day 17</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Ultrasound Insonification Effect Population</title>
            <description>The Ultrasound Insonification Effect Population was to consist of all subjects who received at least 1 hepatic ultrasound insonification and included 14 subjects.&#xD;
The Safety Population was to consist of all subjects who received at least 1 hepatic ultrasound insonification and included 16 subjects.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in Insulin-Mediated EGP Suppression During the Clamp Timepoint With Low Rate Insulin Infusion (Step 1)</title>
          <description>To evaluate the effect of hepatic ultrasound insonification on changes from baseline in whole-body insulin sensitivity during a two-step hyperinsulinemic, euglycemic clamp with stable isotope labeled glucose tracer&#xD;
For each clamp, the degree of EGP suppression from the fasting EGP value was to be determined during the last 30 minutes point during each step of the two-step H-E clamp using the following equation:&#xD;
% EGP suppression = 1 - (EGP clamp/EGP fasting) Partial suppression of EGP during Step 1 was to be assessed to determine hepatic insulin sensitivity and EGP suppression during Step 2 was to be measured to confirm that EGP was (near) fully suppressed to allow the determination of extrahepatic insulin sensitivity.</description>
          <units>percent suppression</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="14"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="10.06" spread="25.294"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Change From Baseline in Rate of Glucose Disappearance (Rd)</title>
        <description>To evaluate the effect of hepatic ultrasound insonification on changes from baseline in whole-body insulin sensitivity during a two-step hyperinsulinemic, euglycemic clamp with stable isotope labeled glucose tracer</description>
        <time_frame>Day 2 (Baseline) to Day 17</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Ultrasound Insonification Effect Population</title>
            <description>The Ultrasound Insonification Effect Population was to consist of all subjects who received at least 1 hepatic ultrasound insonification and included 14 subjects.&#xD;
The Safety Population was to consist of all subjects who received at least 1 hepatic ultrasound insonification and included 16 subjects.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in Rate of Glucose Disappearance (Rd)</title>
          <description>To evaluate the effect of hepatic ultrasound insonification on changes from baseline in whole-body insulin sensitivity during a two-step hyperinsulinemic, euglycemic clamp with stable isotope labeled glucose tracer</description>
          <units>mg/kg/min</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="14"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Clamp Timepoint prior to Insulin Infusion (Fasting)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.004" spread="0.2316"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Clamp Timepoint with Low Rate Insulin Infusion (Step 1)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.663" spread="1.6645"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Clamp Timepoint with High Rate Insulin Infusion (Step 2)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.029" spread="3.2130"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Incidence of Adverse Device Effects (ADEs) With a Severity Score of 1: Treatment Emergent Adverse Events (TEAEs) by System Organ Class and Preferred Term</title>
        <description>To evaluate safety and tolerability of hepatic ultrasound insonification in subjects with T2DM. Incidence of adverse device effects included observations of Incidence and severity of clinically significant laboratory abnormalities, Change from baseline in vital signs (blood pressure, temperature, respiratory rate, and heart rate), Incidence and severity of clinical findings on physical examination, Change from baseline in 12-lead electrocardiogram (ECG) parameters; the primary ECG endpoint was QTcF.&#xD;
To evaluate safety and tolerability of hepatic ultrasound insonification in subjects with T2DM: [Severity Score: 1=Mild; 2=Moderate; 3=Severe; 4=Life-Threatening; 5=Death]</description>
        <time_frame>Screening to Day 28</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Safety Population</title>
            <description>The Safety Population was to consist of all subjects who received at least 1 hepatic ultrasound insonification and included 16 subjects.&#xD;
The Ultrasound Insonification Effect Population was to consist of all subjects who received at least 1 hepatic ultrasound insonification and included 14 subjects.</description>
          </group>
        </group_list>
        <measure>
          <title>Incidence of Adverse Device Effects (ADEs) With a Severity Score of 1: Treatment Emergent Adverse Events (TEAEs) by System Organ Class and Preferred Term</title>
          <description>To evaluate safety and tolerability of hepatic ultrasound insonification in subjects with T2DM. Incidence of adverse device effects included observations of Incidence and severity of clinically significant laboratory abnormalities, Change from baseline in vital signs (blood pressure, temperature, respiratory rate, and heart rate), Incidence and severity of clinical findings on physical examination, Change from baseline in 12-lead electrocardiogram (ECG) parameters; the primary ECG endpoint was QTcF.&#xD;
To evaluate safety and tolerability of hepatic ultrasound insonification in subjects with T2DM: [Severity Score: 1=Mild; 2=Moderate; 3=Severe; 4=Life-Threatening; 5=Death]</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="16"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Subjects with at least one Treatment Emergent Adverse Event (TEAE)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Skin and subcutaneous tissue disorders</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Ecchymosis</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Erythema</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Gastrointestinal disorders</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Abdominal pain</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Dyspepsia</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Vomiting</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>General disorders and administration site conditions</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Infusion site hemorrhage</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Vessel puncture site swelling</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Metabolism and nutrition disorders</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Hypoglycaemia</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Nervous system disorders</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Dizziness</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Vascular disorders</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Thrombophlebitis</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Treatment Emergent Adverse Device Effect (TEADE)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>TEADE Related to Study Procedure</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Serious TEADE</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>TEADE Leading to Study Discontinuation</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Unanticipated Adverse Device Effect (UADE)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Incidence of Clinically Significant Laboratory Abnormalities</title>
        <description>To evaluate safety and tolerability of hepatic ultrasound insonification in subjects with T2DM</description>
        <time_frame>Screening to Day 28</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Safety Population</title>
            <description>The Safety Population was to consist of all subjects who received at least 1 hepatic ultrasound insonification and included 16 subjects.&#xD;
The Ultrasound Insonification Effect Population was to consist of all subjects who received at least 1 hepatic ultrasound insonification and included 14 subjects.</description>
          </group>
        </group_list>
        <measure>
          <title>Incidence of Clinically Significant Laboratory Abnormalities</title>
          <description>To evaluate safety and tolerability of hepatic ultrasound insonification in subjects with T2DM</description>
          <units>clinically significant lab abnormalities</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="16"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Number of Clinically Significant Lab Abnormalities</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Number of Clinically Significant Changes in Hematology Laboratory Values</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Number of Clinically Significant Changes in Hepatic Function Laboratory Values</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Number of Clinically Significant Changes in Renal Function Laboratory Values</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Number of Clinically Significant Changes in Urinalysis Laboratory Values</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Incidence of Significant Clinical Findings on Physical Examination</title>
        <description>To evaluate safety and tolerability of hepatic ultrasound insonification in subjects with T2DM</description>
        <time_frame>Screening to Day 28</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Safety Population</title>
            <description>The Safety Population was to consist of all subjects who received at least 1 hepatic ultrasound insonification and included 16 subjects.&#xD;
The Ultrasound Insonification Effect Population was to consist of all subjects who received at least 1 hepatic ultrasound insonification and included 14 subjects.</description>
          </group>
        </group_list>
        <measure>
          <title>Incidence of Significant Clinical Findings on Physical Examination</title>
          <description>To evaluate safety and tolerability of hepatic ultrasound insonification in subjects with T2DM</description>
          <units>clinically significant phys exam finding</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="16"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in Vital Signs: Blood Pressure</title>
        <description>To evaluate safety and tolerability of hepatic ultrasound insonification in subjects with T2DM</description>
        <time_frame>Baseline to Day 28 - Baseline was defined as the last non-missing value collected prior to the first on study hepatic ultrasound insonification</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Safety Population</title>
            <description>The Safety Population was to consist of all subjects who received at least 1 hepatic ultrasound insonification and included 16 subjects.&#xD;
The Ultrasound Insonification Effect Population was to consist of all subjects who received at least 1 hepatic ultrasound insonification and included 14 subjects.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in Vital Signs: Blood Pressure</title>
          <description>To evaluate safety and tolerability of hepatic ultrasound insonification in subjects with T2DM</description>
          <units>mmHg</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="16"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Change from Baseline in Systolic Blood Pressure</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-3.4" spread="10.89"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change from Baseline in Diastolic Blood Pressure</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-3.0" spread="5.06"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in Vital Signs: Pulse Rate</title>
        <description>To evaluate safety and tolerability of hepatic ultrasound insonification in subjects with T2DM</description>
        <time_frame>Baseline to Day 28 - Baseline was defined as the last non-missing value collected prior to the first on study hepatic ultrasound insonification</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Safety Population</title>
            <description>The Safety Population was to consist of all subjects who received at least 1 hepatic ultrasound insonification and included 16 subjects.&#xD;
The Ultrasound Insonification Effect Population was to consist of all subjects who received at least 1 hepatic ultrasound insonification and included 14 subjects.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in Vital Signs: Pulse Rate</title>
          <description>To evaluate safety and tolerability of hepatic ultrasound insonification in subjects with T2DM</description>
          <units>beats/minute</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="16"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-1.9" spread="10.62"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in Vital Signs: Respiratory Rate</title>
        <description>To evaluate safety and tolerability of hepatic ultrasound insonification in subjects with T2DM</description>
        <time_frame>Baseline to Day 28 - Baseline was defined as the last non-missing value collected prior to the first on study hepatic ultrasound insonification</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Safety Population</title>
            <description>The Safety Population was to consist of all subjects who received at least 1 hepatic ultrasound insonification and included 16 subjects.&#xD;
The Ultrasound Insonification Effect Population was to consist of all subjects who received at least 1 hepatic ultrasound insonification and included 14 subjects.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in Vital Signs: Respiratory Rate</title>
          <description>To evaluate safety and tolerability of hepatic ultrasound insonification in subjects with T2DM</description>
          <units>breaths/minute</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="16"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-1.0" spread="2.28"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in Vital Signs: Temperature</title>
        <description>To evaluate safety and tolerability of hepatic ultrasound insonification in subjects with T2DM</description>
        <time_frame>Baseline to Day 28 - Baseline was defined as the last non-missing value collected prior to the first on study hepatic ultrasound insonification</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Safety Population</title>
            <description>The Safety Population was to consist of all subjects who received at least 1 hepatic ultrasound insonification and included 16 subjects.&#xD;
The Ultrasound Insonification Effect Population was to consist of all subjects who received at least 1 hepatic ultrasound insonification and included 14 subjects.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in Vital Signs: Temperature</title>
          <description>To evaluate safety and tolerability of hepatic ultrasound insonification in subjects with T2DM</description>
          <units>degrees C</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="16"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.07" spread="0.531"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Incidence of Clinically Significant Changes in Vital Sign Values</title>
        <description>To evaluate safety and tolerability of hepatic ultrasound insonification in subjects with T2DM</description>
        <time_frame>Screening to Day 28</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Safety Population</title>
            <description>The Safety Population was to consist of all subjects who received at least 1 hepatic ultrasound insonification and included 16 subjects.&#xD;
The Ultrasound Insonification Effect Population was to consist of all subjects who received at least 1 hepatic ultrasound insonification and included 14 subjects.</description>
          </group>
        </group_list>
        <measure>
          <title>Incidence of Clinically Significant Changes in Vital Sign Values</title>
          <description>To evaluate safety and tolerability of hepatic ultrasound insonification in subjects with T2DM</description>
          <units>clinically significant changes</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="16"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0" spread="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in 12-lead Electrocardiogram (ECG) Parameters</title>
        <description>To evaluate safety and tolerability of hepatic ultrasound insonification in subjects with T2DM</description>
        <time_frame>Baseline to Day 28 - Baseline was defined as the last non-missing value collected prior to the first on study hepatic ultrasound insonification</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Safety Population</title>
            <description>The Safety Population was to consist of all subjects who received at least 1 hepatic ultrasound insonification and included 16 subjects.&#xD;
The Ultrasound Insonification Effect Population was to consist of all subjects who received at least 1 hepatic ultrasound insonification and included 14 subjects.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in 12-lead Electrocardiogram (ECG) Parameters</title>
          <description>To evaluate safety and tolerability of hepatic ultrasound insonification in subjects with T2DM</description>
          <units>msec</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="16"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Change from Baseline in QT Interval</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4.6" spread="20.84"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change from Baseline in PR Interval</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-1.8" spread="15.26"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change from Baseline in QRS Interval</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.1" spread="6.01"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change from Baseline in RR Interval</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="12.4" spread="99.99"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change from Baseline in QTcF Interval</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.4" spread="11.83"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Incidence of Clinically Significant Changes in ECG Measurements</title>
        <description>To evaluate safety and tolerability of hepatic ultrasound insonification in subjects with T2DM</description>
        <time_frame>Screening to Day 28</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Safety Population</title>
            <description>The Safety Population was to consist of all subjects who received at least 1 hepatic ultrasound insonification and included 16 subjects.&#xD;
The Ultrasound Insonification Effect Population was to consist of all subjects who received at least 1 hepatic ultrasound insonification and included 14 subjects.</description>
          </group>
        </group_list>
        <measure>
          <title>Incidence of Clinically Significant Changes in ECG Measurements</title>
          <description>To evaluate safety and tolerability of hepatic ultrasound insonification in subjects with T2DM</description>
          <units>clinically significant changes</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="16"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0" spread="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in Insulin Sensitivity Index (SI)</title>
        <description>To evaluate the effect of hepatic ultrasound insonification on changes from baseline in whole-body insulin sensitivity during a two-step hyperinsulinemic, euglycemic clamp with stable isotope labeled glucose tracer.&#xD;
The Insulin Sensitivity Index was to be calculated from the H-E clamp data using the formula included in the SAP, with Step 1 indicating the first phase of the clamp, or the period of administration of the first (lower) insulin infusion rate and Step 2 indicating the second phase of the clamp or the period of administration of the second (higher) insulin infusion rate. Mean GIRs and mean plasma insulin concentrations were to be calculated during steady state for the applicable step(s).&#xD;
Change from baseline of SI was then to be computed for each subject as:&#xD;
Change from baseline (SI) = SI2 - SI1, where Clamp 2 was the second clamp and Clamp 1 was the first clamp (completed on Day 2, prior to first insonification).</description>
        <time_frame>Day 2 (Baseline) to Day 17</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Ultrasound Insonification Effect Population</title>
            <description>The Ultrasound Insonification Effect Population was to consist of all subjects who received at least 1 hepatic ultrasound insonification and included 14 subjects.&#xD;
The Safety Population was to consist of all subjects who received at least 1 hepatic ultrasound insonification and included 16 subjects.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in Insulin Sensitivity Index (SI)</title>
          <description>To evaluate the effect of hepatic ultrasound insonification on changes from baseline in whole-body insulin sensitivity during a two-step hyperinsulinemic, euglycemic clamp with stable isotope labeled glucose tracer.&#xD;
The Insulin Sensitivity Index was to be calculated from the H-E clamp data using the formula included in the SAP, with Step 1 indicating the first phase of the clamp, or the period of administration of the first (lower) insulin infusion rate and Step 2 indicating the second phase of the clamp or the period of administration of the second (higher) insulin infusion rate. Mean GIRs and mean plasma insulin concentrations were to be calculated during steady state for the applicable step(s).&#xD;
Change from baseline of SI was then to be computed for each subject as:&#xD;
Change from baseline (SI) = SI2 - SI1, where Clamp 2 was the second clamp and Clamp 1 was the first clamp (completed on Day 2, prior to first insonification).</description>
          <units>ml/min per microU/ml</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="14"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.000" spread="0.0132"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in Glucose Disposal Rate During Steady State (M)</title>
        <description>To evaluate the effect of hepatic ultrasound insonification on changes from baseline in whole-body insulin sensitivity during a two-step hyperinsulinemic, euglycemic clamp with stable isotope labeled glucose tracer</description>
        <time_frame>Day 2 (Baseline) to Day 17</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Ultrasound Insonification Effect Population</title>
            <description>The Ultrasound Insonification Effect Population was to consist of all subjects who received at least 1 hepatic ultrasound insonification and included 14 subjects.&#xD;
The Safety Population was to consist of all subjects who received at least 1 hepatic ultrasound insonification and included 16 subjects.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in Glucose Disposal Rate During Steady State (M)</title>
          <description>To evaluate the effect of hepatic ultrasound insonification on changes from baseline in whole-body insulin sensitivity during a two-step hyperinsulinemic, euglycemic clamp with stable isotope labeled glucose tracer</description>
          <units>mg/kg/min</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="14"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Clamp Timepoint with Low Rate Insulin Infusion (Step 1)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.87" spread="1.623"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Clamp Timepoint with High Rate Insulin Infusion (Step 2)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.04" spread="3.161"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in Glucose Metabolic Clearance Rate During Steady State (MCR)</title>
        <description>To evaluate the effect of hepatic ultrasound insonification on changes from baseline in whole-body insulin sensitivity during a two-step hyperinsulinemic, euglycemic clamp with stable isotope labeled glucose tracer</description>
        <time_frame>Day 2 (Baseline) to Day 17</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Ultrasound Insonification Effect Population</title>
            <description>The Ultrasound Insonification Effect Population was to consist of all subjects who received at least 1 hepatic ultrasound insonification and included 14 subjects.&#xD;
The Safety Population was to consist of all subjects who received at least 1 hepatic ultrasound insonification and included 16 subjects.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in Glucose Metabolic Clearance Rate During Steady State (MCR)</title>
          <description>To evaluate the effect of hepatic ultrasound insonification on changes from baseline in whole-body insulin sensitivity during a two-step hyperinsulinemic, euglycemic clamp with stable isotope labeled glucose tracer</description>
          <units>dL/kg/min</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="14"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Clamp Timepoint with Low Rate Insulin Infusion (Step 1)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.81" spread="1.458"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Clamp Timepoint with High Rate Insulin Infusion (Step 2)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.90" spread="3.501"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in Homeostasis Model Assessment of Insulin Resistance (HOMA2-IR)</title>
        <description>To evaluate the effect of hepatic ultrasound insonification on glucose metabolism parameters, assessed by a Homeostasis Model. A higher value denotes an increased level of insulin resistance, and a lower value denotes an decreased level of insulin resistance. The value is computed based on fasting insulin and glucose values.&#xD;
The HOMA2 results were produced by the HOMA2 calculator with FPG and insulin concentration obtained from safety laboratory assessments as the inputs to the calculator at https://www.dtu.ox.ac.uk/homacalculator/. Please see citation (see references module): &quot;Levy 1998 Levy JC, Matthews DR, &amp; Hermans MP. (1998). Correct homeostasis model assessment (HOMA) evaluation uses the computer program. Diabetes Care. 21:2191-2192.&quot;</description>
        <time_frame>Day 15 (Baseline) to Day 18</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Safety Population</title>
            <description>The Safety Population was to consist of all subjects who received at least 1 hepatic ultrasound insonification and included 16 subjects.&#xD;
The Ultrasound Insonification Effect Population was to consist of all subjects who received at least 1 hepatic ultrasound insonification and included 14 subjects.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in Homeostasis Model Assessment of Insulin Resistance (HOMA2-IR)</title>
          <description>To evaluate the effect of hepatic ultrasound insonification on glucose metabolism parameters, assessed by a Homeostasis Model. A higher value denotes an increased level of insulin resistance, and a lower value denotes an decreased level of insulin resistance. The value is computed based on fasting insulin and glucose values.&#xD;
The HOMA2 results were produced by the HOMA2 calculator with FPG and insulin concentration obtained from safety laboratory assessments as the inputs to the calculator at https://www.dtu.ox.ac.uk/homacalculator/. Please see citation (see references module): &quot;Levy 1998 Levy JC, Matthews DR, &amp; Hermans MP. (1998). Correct homeostasis model assessment (HOMA) evaluation uses the computer program. Diabetes Care. 21:2191-2192.&quot;</description>
          <units>score on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="16"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.81" spread="1.018"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in Homeostasis Model Assessment of Insulin Secretion (HOMA2-B)</title>
        <description>To evaluate the effect of hepatic ultrasound insonification on glucose metabolism parameters, assessed by a Homeostasis Model. The HOMA2 results were to be produced by the HOMA2 calculator with FPG and insulin concentration obtained from safety laboratory assessments as the inputs to the calculator at https://www.dtu.ox.ac.uk/homacalculator/. HOMA2-B values estimate steady state pancreatic beta cell function, as a percent of a normal reference population. See citation: &quot;Levy JC, Matthews DR, &amp; Hermans MP. (1998). Correct homeostasis model assessment (HOMA) evaluation uses the computer program. Diabetes Care. 21:2191-2192.&quot;</description>
        <time_frame>Day 15 (Baseline) to Day 18</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Safety Population</title>
            <description>The Safety Population was to consist of all subjects who received at least 1 hepatic ultrasound insonification and included 16 subjects.&#xD;
The Ultrasound Insonification Effect Population was to consist of all subjects who received at least 1 hepatic ultrasound insonification and included 14 subjects.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in Homeostasis Model Assessment of Insulin Secretion (HOMA2-B)</title>
          <description>To evaluate the effect of hepatic ultrasound insonification on glucose metabolism parameters, assessed by a Homeostasis Model. The HOMA2 results were to be produced by the HOMA2 calculator with FPG and insulin concentration obtained from safety laboratory assessments as the inputs to the calculator at https://www.dtu.ox.ac.uk/homacalculator/. HOMA2-B values estimate steady state pancreatic beta cell function, as a percent of a normal reference population. See citation: &quot;Levy JC, Matthews DR, &amp; Hermans MP. (1998). Correct homeostasis model assessment (HOMA) evaluation uses the computer program. Diabetes Care. 21:2191-2192.&quot;</description>
          <units>score on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="16"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-15.92" spread="24.132"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in Fasting Plasma Glucose (FPG)</title>
        <description>To evaluate the effect of hepatic ultrasound insonification on glucose metabolism parameters, assessed by fasting plasma glucose blood test</description>
        <time_frame>Baseline to Day 18 - Baseline was defined as the last non-missing value collected prior to the first on study hepatic ultrasound insonification</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Safety Population</title>
            <description>The Safety Population was to consist of all subjects who received at least 1 hepatic ultrasound insonification and included 16 subjects.&#xD;
The Ultrasound Insonification Effect Population was to consist of all subjects who received at least 1 hepatic ultrasound insonification and included 14 subjects.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in Fasting Plasma Glucose (FPG)</title>
          <description>To evaluate the effect of hepatic ultrasound insonification on glucose metabolism parameters, assessed by fasting plasma glucose blood test</description>
          <units>mg/dL</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="16"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-3.0" spread="20.87"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in Oral Glucose Tolerance Test (OGTT) Area Under the Curve (AUC 0-180): Glucose</title>
        <description>To evaluate the effect of hepatic ultrasound insonification on change from baseline in glucose tolerance and insulin secretion, assessed by an oral glucose tolerance test (OGTT). AUC in this outcome is calculated using the absolute value of glucose measures (compared to incremental AUC below which uses baseline (time 0 glucose) subtracted values).</description>
        <time_frame>Day 1 (Baseline) to Day 16</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Safety Population</title>
            <description>The Safety Population was to consist of all subjects who received at least 1 hepatic ultrasound insonification and included 16 subjects.&#xD;
The Ultrasound Insonification Effect Population was to consist of all subjects who received at least 1 hepatic ultrasound insonification and included 14 subjects.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in Oral Glucose Tolerance Test (OGTT) Area Under the Curve (AUC 0-180): Glucose</title>
          <description>To evaluate the effect of hepatic ultrasound insonification on change from baseline in glucose tolerance and insulin secretion, assessed by an oral glucose tolerance test (OGTT). AUC in this outcome is calculated using the absolute value of glucose measures (compared to incremental AUC below which uses baseline (time 0 glucose) subtracted values).</description>
          <units>(mg hr)/dL</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="16"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Plasma Glucose Total AUC</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-2.112" spread="86.2483"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Plasma Glucose Incremental AUC</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.720" spread="68.7508"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in Oral Glucose Tolerance Test (OGTT) Area Under the Curve (AUC 0-180): Insulin</title>
        <description>To evaluate the effect of hepatic ultrasound insonification on change from baseline in glucose tolerance and insulin secretion, assessed by an oral glucose tolerance test (OGTT). AUC in this outcome is calculated using the absolute value of insulin measures (compared to incremental AUC below which uses baseline (time 0 insulin) subtracted values).</description>
        <time_frame>Day 1 (Baseline) to Day 16</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Safety Population</title>
            <description>The Safety Population was to consist of all subjects who received at least 1 hepatic ultrasound insonification and included 16 subjects.&#xD;
The Ultrasound Insonification Effect Population was to consist of all subjects who received at least 1 hepatic ultrasound insonification and included 14 subjects.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in Oral Glucose Tolerance Test (OGTT) Area Under the Curve (AUC 0-180): Insulin</title>
          <description>To evaluate the effect of hepatic ultrasound insonification on change from baseline in glucose tolerance and insulin secretion, assessed by an oral glucose tolerance test (OGTT). AUC in this outcome is calculated using the absolute value of insulin measures (compared to incremental AUC below which uses baseline (time 0 insulin) subtracted values).</description>
          <units>(mU hr)/L</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="16"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Insulin Total AUC</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="13.580" spread="32.2072"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Insulin Incremental AUC</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="11.777" spread="24.1236"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in Continuous Glucose Monitoring System (CGMS): Time in Ranges</title>
        <description>To evaluate the effect of hepatic ultrasound insonification on glucose metabolism parameters, assessed by a continuous glucose monitoring system (CGMS)</description>
        <time_frame>14:00 on Day -1 to 22:00 on Day 1 (Baseline) to 14:00 on Day 15 to 22:00 on Day 16 - omitting data collected between a subject's OGTT glucose consumption start time + 180 minutes</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Safety Population</title>
            <description>The Safety Population was to consist of all subjects who received at least 1 hepatic ultrasound insonification and included 16 subjects.&#xD;
The Ultrasound Insonification Effect Population was to consist of all subjects who received at least 1 hepatic ultrasound insonification and included 14 subjects.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in Continuous Glucose Monitoring System (CGMS): Time in Ranges</title>
          <description>To evaluate the effect of hepatic ultrasound insonification on glucose metabolism parameters, assessed by a continuous glucose monitoring system (CGMS)</description>
          <units>% Time in Ranges</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="16"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Time &gt;250 mg/dL</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-1.80" spread="8.376"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Time &gt;180 mg/dL</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.90" spread="12.869"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Time 70-180 mg/dL</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.90" spread="12.869"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Time &lt;70 mg/dL</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.00" spread="0.000"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Time &lt;54 mg/dL</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.00" spread="0.000"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in Continuous Glucose Monitoring System (CGMS): Average Daily Glucose</title>
        <description>To evaluate the effect of hepatic ultrasound insonification on glucose metabolism parameters, assessed by a continuous glucose monitoring system (CGMS)</description>
        <time_frame>14:00 on Day -1 to 22:00 on Day 1 (Baseline) to 14:00 on Day 15 to 22:00 on Day 16 - omitting data collected between a subject's OGTT glucose consumption start time + 180 minutes</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Safety Population</title>
            <description>The Safety Population was to consist of all subjects who received at least 1 hepatic ultrasound insonification and included 16 subjects.&#xD;
The Ultrasound Insonification Effect Population was to consist of all subjects who received at least 1 hepatic ultrasound insonification and included 14 subjects.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in Continuous Glucose Monitoring System (CGMS): Average Daily Glucose</title>
          <description>To evaluate the effect of hepatic ultrasound insonification on glucose metabolism parameters, assessed by a continuous glucose monitoring system (CGMS)</description>
          <units>mg/dL</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="16"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-4.807" spread="17.0274"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in Continuous Glucose Monitoring System (CGMS): Blood Glucose Coefficient of Variation</title>
        <description>To evaluate the effect of hepatic ultrasound insonification on glucose metabolism parameters, assessed by a continuous glucose monitoring system (CGMS)</description>
        <time_frame>14:00 on Day -1 to 22:00 on Day 1 (Baseline) to 14:00 on Day 15 to 22:00 on Day 16 - omitting data collected between a subject's OGTT glucose consumption start time + 180 minutes</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Safety Population</title>
            <description>The Safety Population was to consist of all subjects who received at least 1 hepatic ultrasound insonification and included 16 subjects.&#xD;
The Ultrasound Insonification Effect Population was to consist of all subjects who received at least 1 hepatic ultrasound insonification and included 14 subjects.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in Continuous Glucose Monitoring System (CGMS): Blood Glucose Coefficient of Variation</title>
          <description>To evaluate the effect of hepatic ultrasound insonification on glucose metabolism parameters, assessed by a continuous glucose monitoring system (CGMS)</description>
          <units>% Coefficient of Variation</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="16"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-1.58" spread="3.858"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in Continuous Glucose Monitoring System (CGMS): Low/High Blood Glucose Index</title>
        <description>To evaluate the effect of hepatic ultrasound insonification on glucose metabolism parameters, assessed by a continuous glucose monitoring system (CGMS)&#xD;
To calculate the LBGI and HBGI, the original BG data for each day/period was to be transformed such that it was centered by zero and bound between -sqrt(10) and sqrt(10).&#xD;
f(BG,α,β) = [(ln(BG))1.084 - 5.381]*1.509&#xD;
The transformed values were then to be input into the BG risk function:&#xD;
r(BG) = 10 * f(BG,α,β)2&#xD;
The risk of each observation was further to be transformed into two series, risk of low BG series, rl(BG), and risk of high BG series, rh(BG):&#xD;
rl(BG) = r(BG) if f(BG) &lt; 0 and 0 otherwise rh(BG) = r(BG) if f(BG) &gt; 0 and 0 otherwise These series were then to be averaged to produce the LBGI and the HBGI as shown in the equations in the SAP.</description>
        <time_frame>14:00 on Day -1 to 22:00 on Day 1 (Baseline) to 14:00 on Day 15 to 22:00 on Day 16 - omitting data collected between a subject's OGTT glucose consumption start time + 180 minutes</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Safety Population</title>
            <description>The Safety Population was to consist of all subjects who received at least 1 hepatic ultrasound insonification and included 16 subjects.&#xD;
The Ultrasound Insonification Effect Population was to consist of all subjects who received at least 1 hepatic ultrasound insonification and included 14 subjects.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in Continuous Glucose Monitoring System (CGMS): Low/High Blood Glucose Index</title>
          <description>To evaluate the effect of hepatic ultrasound insonification on glucose metabolism parameters, assessed by a continuous glucose monitoring system (CGMS)&#xD;
To calculate the LBGI and HBGI, the original BG data for each day/period was to be transformed such that it was centered by zero and bound between -sqrt(10) and sqrt(10).&#xD;
f(BG,α,β) = [(ln(BG))1.084 - 5.381]*1.509&#xD;
The transformed values were then to be input into the BG risk function:&#xD;
r(BG) = 10 * f(BG,α,β)2&#xD;
The risk of each observation was further to be transformed into two series, risk of low BG series, rl(BG), and risk of high BG series, rh(BG):&#xD;
rl(BG) = r(BG) if f(BG) &lt; 0 and 0 otherwise rh(BG) = r(BG) if f(BG) &gt; 0 and 0 otherwise These series were then to be averaged to produce the LBGI and the HBGI as shown in the equations in the SAP.</description>
          <units>Blood Glucose Index</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="16"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Low Blood Glucose Index (LBGI)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.02" spread="0.056"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>High Blood Glucose Index (HBGI)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.85" spread="2.951"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Incidence of Adverse Device Effects (ADEs) With a Severity Score of 2: Treatment Emergent Adverse Events (TEAEs) by System Organ Class and Preferred Term</title>
        <description>To evaluate safety and tolerability of hepatic ultrasound insonification in subjects with T2DM. Incidence of adverse device effects included observations of Incidence and severity of clinically significant laboratory abnormalities, Change from baseline in vital signs (blood pressure, temperature, respiratory rate, and heart rate), Incidence and severity of clinical findings on physical examination, Change from baseline in 12-lead electrocardiogram (ECG) parameters; the primary ECG endpoint was QTcF.&#xD;
To evaluate safety and tolerability of hepatic ultrasound insonification in subjects with T2DM: [Severity Score: 1=Mild; 2=Moderate; 3=Severe; 4=Life-Threatening; 5=Death]</description>
        <time_frame>Screening to Day 28</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Safety Population</title>
            <description>The Safety Population was to consist of all subjects who received at least 1 hepatic ultrasound insonification and included 16 subjects.&#xD;
The Ultrasound Insonification Effect Population was to consist of all subjects who received at least 1 hepatic ultrasound insonification and included 14 subjects.</description>
          </group>
        </group_list>
        <measure>
          <title>Incidence of Adverse Device Effects (ADEs) With a Severity Score of 2: Treatment Emergent Adverse Events (TEAEs) by System Organ Class and Preferred Term</title>
          <description>To evaluate safety and tolerability of hepatic ultrasound insonification in subjects with T2DM. Incidence of adverse device effects included observations of Incidence and severity of clinically significant laboratory abnormalities, Change from baseline in vital signs (blood pressure, temperature, respiratory rate, and heart rate), Incidence and severity of clinical findings on physical examination, Change from baseline in 12-lead electrocardiogram (ECG) parameters; the primary ECG endpoint was QTcF.&#xD;
To evaluate safety and tolerability of hepatic ultrasound insonification in subjects with T2DM: [Severity Score: 1=Mild; 2=Moderate; 3=Severe; 4=Life-Threatening; 5=Death]</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="16"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Subjects with at least one Treatment Emergent Adverse Event (TEAE)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Skin and subcutaneous tissue disorders</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Ecchymosis</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Erythema</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Gastrointestinal disorders</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Abdominal pain</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Dyspepsia</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Vomiting</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>General disorders and administration site conditions</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Infusion site hemorrhage</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Vessel puncture site swelling</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Metabolism and nutrition disorders</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Hypoglycaemia</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Nervous system disorders</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Dizziness</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Vascular disorders</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Thrombophlebitis</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Treatment Emergent Adverse Device Effect (TEADE)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>TEADE Related to Study Procedure</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Serious TEADE</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>TEADE Leading to Study Discontinuation</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Unanticipated Adverse Device Effect (UADE)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Incidence of Adverse Device Effects (ADEs) With a Severity Score of 3: Treatment Emergent Adverse Events (TEAEs) by System Organ Class and Preferred Term</title>
        <description>To evaluate safety and tolerability of hepatic ultrasound insonification in subjects with T2DM. Incidence of adverse device effects included observations of Incidence and severity of clinically significant laboratory abnormalities, Change from baseline in vital signs (blood pressure, temperature, respiratory rate, and heart rate), Incidence and severity of clinical findings on physical examination, Change from baseline in 12-lead electrocardiogram (ECG) parameters; the primary ECG endpoint was QTcF.&#xD;
To evaluate safety and tolerability of hepatic ultrasound insonification in subjects with T2DM: [Severity Score: 1=Mild; 2=Moderate; 3=Severe; 4=Life-Threatening; 5=Death]</description>
        <time_frame>Screening to Day 28</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Safety Population</title>
            <description>The Safety Population was to consist of all subjects who received at least 1 hepatic ultrasound insonification and included 16 subjects.&#xD;
The Ultrasound Insonification Effect Population was to consist of all subjects who received at least 1 hepatic ultrasound insonification and included 14 subjects.</description>
          </group>
        </group_list>
        <measure>
          <title>Incidence of Adverse Device Effects (ADEs) With a Severity Score of 3: Treatment Emergent Adverse Events (TEAEs) by System Organ Class and Preferred Term</title>
          <description>To evaluate safety and tolerability of hepatic ultrasound insonification in subjects with T2DM. Incidence of adverse device effects included observations of Incidence and severity of clinically significant laboratory abnormalities, Change from baseline in vital signs (blood pressure, temperature, respiratory rate, and heart rate), Incidence and severity of clinical findings on physical examination, Change from baseline in 12-lead electrocardiogram (ECG) parameters; the primary ECG endpoint was QTcF.&#xD;
To evaluate safety and tolerability of hepatic ultrasound insonification in subjects with T2DM: [Severity Score: 1=Mild; 2=Moderate; 3=Severe; 4=Life-Threatening; 5=Death]</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="16"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Subjects with at least one Treatment Emergent Adverse Event (TEAE)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Skin and subcutaneous tissue disorders</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Ecchymosis</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Erythema</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Gastrointestinal disorders</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Abdominal pain</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Dyspepsia</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Vomiting</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>General disorders and administration site conditions</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Infusion site hemorrhage</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Vessel puncture site swelling</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Metabolism and nutrition disorders</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Hypoglycaemia</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Nervous system disorders</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Dizziness</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Vascular disorders</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Thrombophlebitis</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Treatment Emergent Adverse Device Effect (TEADE)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>TEADE Related to Study Procedure</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Serious TEADE</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>TEADE Leading to Study Discontinuation</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Unanticipated Adverse Device Effect (UADE)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Incidence of Adverse Device Effects (ADEs) With a Severity Score of 4: Treatment Emergent Adverse Events (TEAEs) by System Organ Class and Preferred Term</title>
        <description>To evaluate safety and tolerability of hepatic ultrasound insonification in subjects with T2DM. Incidence of adverse device effects included observations of Incidence and severity of clinically significant laboratory abnormalities, Change from baseline in vital signs (blood pressure, temperature, respiratory rate, and heart rate), Incidence and severity of clinical findings on physical examination, Change from baseline in 12-lead electrocardiogram (ECG) parameters; the primary ECG endpoint was QTcF.&#xD;
To evaluate safety and tolerability of hepatic ultrasound insonification in subjects with T2DM: [Severity Score: 1=Mild; 2=Moderate; 3=Severe; 4=Life-Threatening; 5=Death]</description>
        <time_frame>Screening to Day 28</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Safety Population</title>
            <description>The Safety Population was to consist of all subjects who received at least 1 hepatic ultrasound insonification and included 16 subjects.&#xD;
The Ultrasound Insonification Effect Population was to consist of all subjects who received at least 1 hepatic ultrasound insonification and included 14 subjects.</description>
          </group>
        </group_list>
        <measure>
          <title>Incidence of Adverse Device Effects (ADEs) With a Severity Score of 4: Treatment Emergent Adverse Events (TEAEs) by System Organ Class and Preferred Term</title>
          <description>To evaluate safety and tolerability of hepatic ultrasound insonification in subjects with T2DM. Incidence of adverse device effects included observations of Incidence and severity of clinically significant laboratory abnormalities, Change from baseline in vital signs (blood pressure, temperature, respiratory rate, and heart rate), Incidence and severity of clinical findings on physical examination, Change from baseline in 12-lead electrocardiogram (ECG) parameters; the primary ECG endpoint was QTcF.&#xD;
To evaluate safety and tolerability of hepatic ultrasound insonification in subjects with T2DM: [Severity Score: 1=Mild; 2=Moderate; 3=Severe; 4=Life-Threatening; 5=Death]</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="16"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Subjects with at least one Treatment Emergent Adverse Event (TEAE)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Skin and subcutaneous tissue disorders</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Ecchymosis</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Erythema</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Gastrointestinal disorders</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Abdominal pain</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Dyspepsia</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Vomiting</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>General disorders and administration site conditions</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Infusion site hemorrhage</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Vessel puncture site swelling</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Metabolism and nutrition disorders</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Hypoglycaemia</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Nervous system disorders</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Dizziness</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Vascular disorders</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Thrombophlebitis</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Treatment Emergent Adverse Device Effect (TEADE)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>TEADE Related to Study Procedure</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Serious TEADE</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>TEADE Leading to Study Discontinuation</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Unanticipated Adverse Device Effect (UADE)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Incidence of Adverse Device Effects (ADEs) With a Severity Score of 5: Treatment Emergent Adverse Events (TEAEs) by System Organ Class and Preferred Term</title>
        <description>To evaluate safety and tolerability of hepatic ultrasound insonification in subjects with T2DM. Incidence of adverse device effects included observations of Incidence and severity of clinically significant laboratory abnormalities, Change from baseline in vital signs (blood pressure, temperature, respiratory rate, and heart rate), Incidence and severity of clinical findings on physical examination, Change from baseline in 12-lead electrocardiogram (ECG) parameters; the primary ECG endpoint was QTcF.&#xD;
To evaluate safety and tolerability of hepatic ultrasound insonification in subjects with T2DM: [Severity Score: 1=Mild; 2=Moderate; 3=Severe; 4=Life-Threatening; 5=Death]</description>
        <time_frame>Screening to Day 28</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Safety Population</title>
            <description>The Safety Population was to consist of all subjects who received at least 1 hepatic ultrasound insonification and included 16 subjects.&#xD;
The Ultrasound Insonification Effect Population was to consist of all subjects who received at least 1 hepatic ultrasound insonification and included 14 subjects.</description>
          </group>
        </group_list>
        <measure>
          <title>Incidence of Adverse Device Effects (ADEs) With a Severity Score of 5: Treatment Emergent Adverse Events (TEAEs) by System Organ Class and Preferred Term</title>
          <description>To evaluate safety and tolerability of hepatic ultrasound insonification in subjects with T2DM. Incidence of adverse device effects included observations of Incidence and severity of clinically significant laboratory abnormalities, Change from baseline in vital signs (blood pressure, temperature, respiratory rate, and heart rate), Incidence and severity of clinical findings on physical examination, Change from baseline in 12-lead electrocardiogram (ECG) parameters; the primary ECG endpoint was QTcF.&#xD;
To evaluate safety and tolerability of hepatic ultrasound insonification in subjects with T2DM: [Severity Score: 1=Mild; 2=Moderate; 3=Severe; 4=Life-Threatening; 5=Death]</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="16"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Subjects with at least one Treatment Emergent Adverse Event (TEAE)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Skin and subcutaneous tissue disorders</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Ecchymosis</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Erythema</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Gastrointestinal disorders</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Abdominal pain</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Dyspepsia</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Vomiting</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>General disorders and administration site conditions</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Infusion site hemorrhage</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Vessel puncture site swelling</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Metabolism and nutrition disorders</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Hypoglycaemia</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Nervous system disorders</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Dizziness</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Vascular disorders</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Thrombophlebitis</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Treatment Emergent Adverse Device Effect (TEADE)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>TEADE Related to Study Procedure</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Serious TEADE</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>TEADE Leading to Study Discontinuation</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Unanticipated Adverse Device Effect (UADE)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Other Pre-specified</type>
        <title>Change From Baseline in Exploratory Biomarkers</title>
        <description>To evaluate the effect of hepatic ultrasound insonification on glucose metabolism parameters, as assessed by exploratory markers in blood samples</description>
        <time_frame>Baseline to Day 18 - Baseline was defined as the last non-missing value collected prior to the first on study hepatic ultrasound insonification</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Safety Population</title>
            <description>The Safety Population was to consist of all subjects who received at least 1 hepatic ultrasound insonification and included 16 subjects.&#xD;
The Ultrasound Insonification Effect Population was to consist of all subjects who received at least 1 hepatic ultrasound insonification and included 14 subjects.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in Exploratory Biomarkers</title>
          <description>To evaluate the effect of hepatic ultrasound insonification on glucose metabolism parameters, as assessed by exploratory markers in blood samples</description>
          <units>ng/L</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="16"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Ghrelin</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.5" spread="37.05"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Glucagon</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-13.7" spread="25.17"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Glucagon-Like Peptide-1</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-26.840" spread="48.8059"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Leptin</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2770" spread="6490"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Other Pre-specified</type>
        <title>Change From Baseline in Long-term Glucose Parameters: Fructosamine</title>
        <description>To evaluate the effect of hepatic ultrasound insonification on glucose metabolism parameters, as assessed by long-term glucose markers in blood samples</description>
        <time_frame>Baseline to Day 18 - Baseline was defined as the last non-missing value collected prior to the first on study hepatic ultrasound insonification</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Safety Population</title>
            <description>The Safety Population was to consist of all subjects who received at least 1 hepatic ultrasound insonification and included 16 subjects.&#xD;
The Ultrasound Insonification Effect Population was to consist of all subjects who received at least 1 hepatic ultrasound insonification and included 14 subjects.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in Long-term Glucose Parameters: Fructosamine</title>
          <description>To evaluate the effect of hepatic ultrasound insonification on glucose metabolism parameters, as assessed by long-term glucose markers in blood samples</description>
          <units>micromol/L</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="16"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-17.8" spread="18.35"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Other Pre-specified</type>
        <title>Change From Baseline in Long-term Glucose Parameters: Hemoglobin A1C</title>
        <description>To evaluate the effect of hepatic ultrasound insonification on glucose metabolism parameters, as assessed by long-term glucose markers in blood samples</description>
        <time_frame>Baseline to Day 18 - Baseline was defined as the last non-missing value collected prior to the first on study hepatic ultrasound insonification</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Safety Population</title>
            <description>The Safety Population was to consist of all subjects who received at least 1 hepatic ultrasound insonification and included 16 subjects.&#xD;
The Ultrasound Insonification Effect Population was to consist of all subjects who received at least 1 hepatic ultrasound insonification and included 14 subjects.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in Long-term Glucose Parameters: Hemoglobin A1C</title>
          <description>To evaluate the effect of hepatic ultrasound insonification on glucose metabolism parameters, as assessed by long-term glucose markers in blood samples</description>
          <units>% A1C</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="16"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.11" spread="0.162"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Other Pre-specified</type>
        <title>Change From Baseline in Lipid Metabolism Parameters: Cholesterol and Triglycerides</title>
        <description>To evaluate the effect of hepatic ultrasound insonification on glucose metabolism parameters, as assessed by lipid metabolism markers in blood samples</description>
        <time_frame>Baseline to Day 18 - Baseline was defined as the last non-missing value collected prior to the first on study hepatic ultrasound insonification</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Safety Population</title>
            <description>The Safety Population was to consist of all subjects who received at least 1 hepatic ultrasound insonification and included 16 subjects.&#xD;
The Ultrasound Insonification Effect Population was to consist of all subjects who received at least 1 hepatic ultrasound insonification and included 14 subjects.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in Lipid Metabolism Parameters: Cholesterol and Triglycerides</title>
          <description>To evaluate the effect of hepatic ultrasound insonification on glucose metabolism parameters, as assessed by lipid metabolism markers in blood samples</description>
          <units>mg/dL</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="16"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Change from Baseline in Cholesterol</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-10.9" spread="17.00"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change from Baseline in HDL Cholesterol</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-3.9" spread="4.90"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change from Baseline in LDL Cholesterol</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-4.9" spread="14.80"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change from Baseline in VLDL Cholesterol</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-2.1" spread="5.34"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change from Baseline in Triglycerides</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-14.3" spread="33.12"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Other Pre-specified</type>
        <title>Change From Baseline in Lipid Metabolism Parameters: Free Fatty Acids</title>
        <description>To evaluate the effect of hepatic ultrasound insonification on glucose metabolism parameters, as assessed by lipid metabolism markers in blood samples</description>
        <time_frame>Baseline to Day 18 - Baseline was defined as the last non-missing value collected prior to the first on study hepatic ultrasound insonification</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Safety Population</title>
            <description>The Safety Population was to consist of all subjects who received at least 1 hepatic ultrasound insonification and included 16 subjects.&#xD;
The Ultrasound Insonification Effect Population was to consist of all subjects who received at least 1 hepatic ultrasound insonification and included 14 subjects.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in Lipid Metabolism Parameters: Free Fatty Acids</title>
          <description>To evaluate the effect of hepatic ultrasound insonification on glucose metabolism parameters, as assessed by lipid metabolism markers in blood samples</description>
          <units>mEq/L</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="16"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.02" spread="0.286"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Other Pre-specified</type>
        <title>Change From Baseline in Inflammatory Biomarkers: Adiponectin</title>
        <description>To evaluate the effect of hepatic ultrasound insonification on glucose metabolism parameters, as assessed by inflammatory biomarkers in blood samples</description>
        <time_frame>Baseline to Day 18 - Baseline was defined as the last non-missing value collected prior to the first on study hepatic ultrasound insonification</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Safety Population</title>
            <description>The Safety Population was to consist of all subjects who received at least 1 hepatic ultrasound insonification and included 16 subjects.&#xD;
The Ultrasound Insonification Effect Population was to consist of all subjects who received at least 1 hepatic ultrasound insonification and included 14 subjects.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in Inflammatory Biomarkers: Adiponectin</title>
          <description>To evaluate the effect of hepatic ultrasound insonification on glucose metabolism parameters, as assessed by inflammatory biomarkers in blood samples</description>
          <units>mg/L</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="16"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.70" spread="0.896"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Other Pre-specified</type>
        <title>Change From Baseline in Inflammatory Biomarkers: C Reactive Protein</title>
        <description>To evaluate the effect of hepatic ultrasound insonification on glucose metabolism parameters, as assessed by inflammatory biomarkers in blood samples</description>
        <time_frame>Baseline to Day 18 - Baseline was defined as the last non-missing value collected prior to the first on study hepatic ultrasound insonification</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Safety Population</title>
            <description>The Safety Population was to consist of all subjects who received at least 1 hepatic ultrasound insonification and included 16 subjects.&#xD;
The Ultrasound Insonification Effect Population was to consist of all subjects who received at least 1 hepatic ultrasound insonification and included 14 subjects.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in Inflammatory Biomarkers: C Reactive Protein</title>
          <description>To evaluate the effect of hepatic ultrasound insonification on glucose metabolism parameters, as assessed by inflammatory biomarkers in blood samples</description>
          <units>mg/L</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="16"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.1" spread="1.13"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Other Pre-specified</type>
        <title>Change From Baseline in Inflammatory Biomarkers: Interleukin-6</title>
        <description>To evaluate the effect of hepatic ultrasound insonification on glucose metabolism parameters, as assessed by inflammatory biomarkers in blood samples</description>
        <time_frame>Baseline to Day 18 - Baseline was defined as the last non-missing value collected prior to the first on study hepatic ultrasound insonification</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Safety Population</title>
            <description>The Safety Population was to consist of all subjects who received at least 1 hepatic ultrasound insonification and included 16 subjects.&#xD;
The Ultrasound Insonification Effect Population was to consist of all subjects who received at least 1 hepatic ultrasound insonification and included 14 subjects.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in Inflammatory Biomarkers: Interleukin-6</title>
          <description>To evaluate the effect of hepatic ultrasound insonification on glucose metabolism parameters, as assessed by inflammatory biomarkers in blood samples</description>
          <units>ng/L</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="16"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.29" spread="1.445"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Assessing the safety and tolerability profile of hepatic ultrasound insonification in subjects with T2DM was an integral objective of this study; adverse event data was collected for study duration (Screening to Day 28).</time_frame>
      <desc>TEAE was defined as any undesirable and unintended medical event occurring to a subject from the subject's first hepatic ultrasound insonification until post-treatment follow-up. The skin and subcutaneous tissue disorders, GI disorders, general disorders, metabolism and nutrition disorders, nervous system disorders and vascular disorders were not attributable to the device, as no TEADEs were recorded in the study.</desc>
      <group_list>
        <group group_id="E1">
          <title>Safety Population</title>
          <description>The Safety Population was to consist of all subjects who received at least 1 hepatic ultrasound insonification and included 16 subjects (44.4%).</description>
        </group>
      </group_list>
      <serious_events>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="16"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <default_vocab>MedDRA Version 23.0</default_vocab>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="7" subjects_at_risk="16"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Abdominal pain</sub_title>
                <description>The skin and subcutaneous tissue disorders, GI disorders, general disorders, metabolism and nutrition disorders, nervous system disorders and vascular disorders were not attributable to the device, as no TEADEs were recorded in the study.</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Dyspepsia</sub_title>
                <description>The skin and subcutaneous tissue disorders, GI disorders, general disorders, metabolism and nutrition disorders, nervous system disorders and vascular disorders were not attributable to the device, as no TEADEs were recorded in the study.</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Vomiting</sub_title>
                <description>The skin and subcutaneous tissue disorders, GI disorders, general disorders, metabolism and nutrition disorders, nervous system disorders and vascular disorders were not attributable to the device, as no TEADEs were recorded in the study.</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="16"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Infusion site haemorrhage</sub_title>
                <description>The skin and subcutaneous tissue disorders, GI disorders, general disorders, metabolism and nutrition disorders, nervous system disorders and vascular disorders were not attributable to the device, as no TEADEs were recorded in the study.</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Vessel puncture site swelling</sub_title>
                <description>The skin and subcutaneous tissue disorders, GI disorders, general disorders, metabolism and nutrition disorders, nervous system disorders and vascular disorders were not attributable to the device, as no TEADEs were recorded in the study.</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="16"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Hypoglycaemia</sub_title>
                <description>The skin and subcutaneous tissue disorders, GI disorders, general disorders, metabolism and nutrition disorders, nervous system disorders and vascular disorders were not attributable to the device, as no TEADEs were recorded in the study.</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="16"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Dizziness</sub_title>
                <description>The skin and subcutaneous tissue disorders, GI disorders, general disorders, metabolism and nutrition disorders, nervous system disorders and vascular disorders were not attributable to the device, as no TEADEs were recorded in the study.</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="16"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Ecchymosis</sub_title>
                <description>The skin and subcutaneous tissue disorders, GI disorders, general disorders, metabolism and nutrition disorders, nervous system disorders and vascular disorders were not attributable to the device, as no TEADEs were recorded in the study.</description>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Erythema</sub_title>
                <description>The skin and subcutaneous tissue disorders, GI disorders, general disorders, metabolism and nutrition disorders, nervous system disorders and vascular disorders were not attributable to the device, as no TEADEs were recorded in the study.</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="16"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Thrombophlebitis</sub_title>
                <description>The skin and subcutaneous tissue disorders, GI disorders, general disorders, metabolism and nutrition disorders, nervous system disorders and vascular disorders were not attributable to the device, as no TEADEs were recorded in the study.</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="16"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>Principal Investigators are NOT employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.</restrictive_agreement>
    </certain_agreements>
    <limitations_and_caveats>The Safety Population consisted of subjects who received hepatic ultrasound insonification and included 16 subjects. The Ultrasound Insonification Effect Population consisted of subjects who received hepatic ultrasound insonification and included 15 subjects. Subject 101-029 had unevaluable data and was excluded from Ultrasound Insonification Effect Population. Subject 101-012 had clamp protocol deviation, and Ultrasound Insonification Effect Population was also analyzed excluding subject.</limitations_and_caveats>
    <point_of_contact>
      <name_or_title>Diane Minas</name_or_title>
      <organization>GE Research</organization>
      <phone>(518)698-3959</phone>
      <email>minas@ge.com</email>
    </point_of_contact>
  </clinical_results>
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT04502212
org study id: GE Research HUI-01
nct id: NCT04502212
lead sponsor: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: Yes
is us export: Yes
This research study is being done to evaluate the effect of hepatic ultrasound insonification
      on whole-body insulin sensitivity and evaluate the safety and tolerability of hepatic
      ultrasound insonification in subjects with Type 2 Diabetes Mellitus (T2DM).
      "Insonify/insonification" is defined as applying to an area or an object carefully-controlled
      sound waves, typically as in ultrasound imaging. GE Research is sponsoring this research
      study. The purpose of this research study is to:

        -  Evaluate the effect of liver ultrasound waves on changes from baseline in whole-body
           insulin sensitivity

        -  Test the safety and tolerability of liver ultrasound waves in subjects with Type 2
           Diabetes Mellitus

        -  Evaluate the effect of liver ultrasound waves on change from baseline in glucose
           tolerance and insulin secretion

        -  Evaluate the effect of liver ultrasound waves on glucose metabolism

      Insulin sensitivity refers to how sensitive the body's cells are in response to insulin.

      Glucose tolerance refers to the body's ability to handle (tolerate) glucose. Insulin
      secretion is a process in which the body releases insulin in response to glucose levels in
      the blood becoming elevated.

      The study device used in this study is cleared for use by the United States Food and Drug
      Administration (FDA) for ultrasound diagnostic exams, however it has not been tested or
      approved specifically for modulation of metabolism in people with diabetes. The use of the
      study device in this study is investigational and is considered a Non-Significant Risk (NSR).
This was an open label, exploratory pilot study to assess the effects of hepatic ultrasound
      insonification on glucometabolic parameters in subjects with T2DM through selective hepatic
      ultrasound of the porta hepatis region of the liver utilizing pulsed ultrasound. The study
      was to consist of 1 cohort comprising up to 15 subjects. Dropouts and withdrawals could have
      been replaced until the anticipated number of subjects completed the study. Finally, the
      study consisted of one cohort with 36 subjects enrolled, including 20 screen failures, 15
      subjects that completed the study (1 completer had an incorrect infusion parameter and was
      removed from clamp analysis), and 1 subject that was discontinued at the discretion of the
      Investigator. As this was an exploratory, open-label study, no randomization or blinding was
      performed and no-unblinding codes were required.

      The study included a Screening Period, Observational Period 1, 3 consecutive days of hepatic
      ultrasound insonification, and Observational Period 2. Each Observational Period was divided
      into an In-house Period and an Outpatient Visit (OPV). The Screening Period was performed up
      to 28 days prior to the first In-house Period. For eligible subjects with a body mass index
      (BMI) > 35.0 and ≤ 40.0 kg/m2 and/or a waist circumference > 40 and ≤ 45 inches, an
      ultrasound examination was added to confirm eligibility, and the Screening Period was
      extended to at least 30 days. The first Observational Period lasted approximately 2-weeks
      (Days -1 to 14). On the morning of Day -1, subjects checked into the clinic for a 3-day
      In-house Period; subjects may have been released from the clinic on Day 2. Subjects were
      contacted via telephone every other day until the next In-house Period. On Day 8, subjects
      checked into the clinic for an OPV. On Day 15, subjects checked into the clinic in fasting
      conditions for a 4-day In-house Period. Insonifications were performed on three consecutive
      days (Days 15, 16 and 17). Subjects may have been released from the clinic on Day 18. The
      second Observational Period lasted 11 days (Days 18 to 28). Subjects were contacted via
      telephone every other day until the Follow-up Visit. On Day 22, subjects checked into the
      clinic for the OPV. The Follow-up Visit was performed on Day 28.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Other
masking: None (Open Label)
measure: Change From Baseline in Glucose Disposal Rate: Insulin Ratio During Steady State (M/I)
time frame: Day 2 (Baseline) to Day 17
description: To evaluate the effect of hepatic ultrasound insonification on changes from baseline in whole-body insulin sensitivity during a two-step hyperinsulinemic, euglycemic clamp with stable isotope labeled glucose tracer
measure: Change From Baseline in Endogenous Glucose Production (EGP)
time frame: Day 2 (Baseline) to Day 17
description: To evaluate the effect of hepatic ultrasound insonification on changes from baseline in whole-body insulin sensitivity during a two-step hyperinsulinemic, euglycemic clamp with stable isotope labeled glucose tracer
measure: Change From Baseline in Insulin-Mediated EGP Suppression During the Clamp Timepoint With Low Rate Insulin Infusion (Step 1)
time frame: Day 2 (Baseline) to Day 17
description: To evaluate the effect of hepatic ultrasound insonification on changes from baseline in whole-body insulin sensitivity during a two-step hyperinsulinemic, euglycemic clamp with stable isotope labeled glucose tracer
For each clamp, the degree of EGP suppression from the fasting EGP value was to be determined during the last 30 minutes point during each step of the two-step H-E clamp using the following equation:
% EGP suppression = 1 - (EGP clamp/EGP fasting) Partial suppression of EGP during Step 1 was to be assessed to determine hepatic insulin sensitivity and EGP suppression during Step 2 was to be measured to confirm that EGP was (near) fully suppressed to allow the determination of extrahepatic insulin sensitivity.
measure: Change From Baseline in Rate of Glucose Disappearance (Rd)
time frame: Day 2 (Baseline) to Day 17
description: To evaluate the effect of hepatic ultrasound insonification on changes from baseline in whole-body insulin sensitivity during a two-step hyperinsulinemic, euglycemic clamp with stable isotope labeled glucose tracer
measure: Incidence of Adverse Device Effects (ADEs) With a Severity Score of 1: Treatment Emergent Adverse Events (TEAEs) by System Organ Class and Preferred Term
time frame: Screening to Day 28
description: To evaluate safety and tolerability of hepatic ultrasound insonification in subjects with T2DM. Incidence of adverse device effects included observations of Incidence and severity of clinically significant laboratory abnormalities, Change from baseline in vital signs (blood pressure, temperature, respiratory rate, and heart rate), Incidence and severity of clinical findings on physical examination, Change from baseline in 12-lead electrocardiogram (ECG) parameters; the primary ECG endpoint was QTcF.
To evaluate safety and tolerability of hepatic ultrasound insonification in subjects with T2DM: [Severity Score: 1=Mild; 2=Moderate; 3=Severe; 4=Life-Threatening; 5=Death]
measure: Incidence of Clinically Significant Laboratory Abnormalities
time frame: Screening to Day 28
description: To evaluate safety and tolerability of hepatic ultrasound insonification in subjects with T2DM
measure: Incidence of Significant Clinical Findings on Physical Examination
time frame: Screening to Day 28
description: To evaluate safety and tolerability of hepatic ultrasound insonification in subjects with T2DM
measure: Change From Baseline in Vital Signs: Blood Pressure
time frame: Baseline to Day 28 - Baseline was defined as the last non-missing value collected prior to the first on study hepatic ultrasound insonification
description: To evaluate safety and tolerability of hepatic ultrasound insonification in subjects with T2DM
measure: Change From Baseline in Vital Signs: Pulse Rate
time frame: Baseline to Day 28 - Baseline was defined as the last non-missing value collected prior to the first on study hepatic ultrasound insonification
description: To evaluate safety and tolerability of hepatic ultrasound insonification in subjects with T2DM
measure: Change From Baseline in Vital Signs: Respiratory Rate
time frame: Baseline to Day 28 - Baseline was defined as the last non-missing value collected prior to the first on study hepatic ultrasound insonification
description: To evaluate safety and tolerability of hepatic ultrasound insonification in subjects with T2DM
measure: Change From Baseline in Vital Signs: Temperature
time frame: Baseline to Day 28 - Baseline was defined as the last non-missing value collected prior to the first on study hepatic ultrasound insonification
description: To evaluate safety and tolerability of hepatic ultrasound insonification in subjects with T2DM
measure: Incidence of Clinically Significant Changes in Vital Sign Values
time frame: Screening to Day 28
description: To evaluate safety and tolerability of hepatic ultrasound insonification in subjects with T2DM
measure: Change From Baseline in 12-lead Electrocardiogram (ECG) Parameters
time frame: Baseline to Day 28 - Baseline was defined as the last non-missing value collected prior to the first on study hepatic ultrasound insonification
description: To evaluate safety and tolerability of hepatic ultrasound insonification in subjects with T2DM
measure: Incidence of Clinically Significant Changes in ECG Measurements
time frame: Screening to Day 28
description: To evaluate safety and tolerability of hepatic ultrasound insonification in subjects with T2DM
measure: Change From Baseline in Insulin Sensitivity Index (SI)
time frame: Day 2 (Baseline) to Day 17
description: To evaluate the effect of hepatic ultrasound insonification on changes from baseline in whole-body insulin sensitivity during a two-step hyperinsulinemic, euglycemic clamp with stable isotope labeled glucose tracer.
The Insulin Sensitivity Index was to be calculated from the H-E clamp data using the formula included in the SAP, with Step 1 indicating the first phase of the clamp, or the period of administration of the first (lower) insulin infusion rate and Step 2 indicating the second phase of the clamp or the period of administration of the second (higher) insulin infusion rate. Mean GIRs and mean plasma insulin concentrations were to be calculated during steady state for the applicable step(s).
Change from baseline of SI was then to be computed for each subject as:
Change from baseline (SI) = SI2 - SI1, where Clamp 2 was the second clamp and Clamp 1 was the first clamp (completed on Day 2, prior to first insonification).
measure: Change From Baseline in Glucose Disposal Rate During Steady State (M)
time frame: Day 2 (Baseline) to Day 17
description: To evaluate the effect of hepatic ultrasound insonification on changes from baseline in whole-body insulin sensitivity during a two-step hyperinsulinemic, euglycemic clamp with stable isotope labeled glucose tracer
measure: Change From Baseline in Glucose Metabolic Clearance Rate During Steady State (MCR)
time frame: Day 2 (Baseline) to Day 17
description: To evaluate the effect of hepatic ultrasound insonification on changes from baseline in whole-body insulin sensitivity during a two-step hyperinsulinemic, euglycemic clamp with stable isotope labeled glucose tracer
measure: Change From Baseline in Homeostasis Model Assessment of Insulin Resistance (HOMA2-IR)
time frame: Day 15 (Baseline) to Day 18
description: To evaluate the effect of hepatic ultrasound insonification on glucose metabolism parameters, assessed by a Homeostasis Model. A higher value denotes an increased level of insulin resistance, and a lower value denotes an decreased level of insulin resistance. The value is computed based on fasting insulin and glucose values.
The HOMA2 results were produced by the HOMA2 calculator with FPG and insulin concentration obtained from safety laboratory assessments as the inputs to the calculator at https://www.dtu.ox.ac.uk/homacalculator/. Please see citation (see references module): "Levy 1998 Levy JC, Matthews DR, & Hermans MP. (1998). Correct homeostasis model assessment (HOMA) evaluation uses the computer program. Diabetes Care. 21:2191-2192."
measure: Change From Baseline in Homeostasis Model Assessment of Insulin Secretion (HOMA2-B)
time frame: Day 15 (Baseline) to Day 18
description: To evaluate the effect of hepatic ultrasound insonification on glucose metabolism parameters, assessed by a Homeostasis Model. The HOMA2 results were to be produced by the HOMA2 calculator with FPG and insulin concentration obtained from safety laboratory assessments as the inputs to the calculator at https://www.dtu.ox.ac.uk/homacalculator/. HOMA2-B values estimate steady state pancreatic beta cell function, as a percent of a normal reference population. See citation: "Levy JC, Matthews DR, & Hermans MP. (1998). Correct homeostasis model assessment (HOMA) evaluation uses the computer program. Diabetes Care. 21:2191-2192."
measure: Change From Baseline in Fasting Plasma Glucose (FPG)
time frame: Baseline to Day 18 - Baseline was defined as the last non-missing value collected prior to the first on study hepatic ultrasound insonification
description: To evaluate the effect of hepatic ultrasound insonification on glucose metabolism parameters, assessed by fasting plasma glucose blood test
measure: Change From Baseline in Oral Glucose Tolerance Test (OGTT) Area Under the Curve (AUC 0-180): Glucose
time frame: Day 1 (Baseline) to Day 16
description: To evaluate the effect of hepatic ultrasound insonification on change from baseline in glucose tolerance and insulin secretion, assessed by an oral glucose tolerance test (OGTT). AUC in this outcome is calculated using the absolute value of glucose measures (compared to incremental AUC below which uses baseline (time 0 glucose) subtracted values).
measure: Change From Baseline in Oral Glucose Tolerance Test (OGTT) Area Under the Curve (AUC 0-180): Insulin
time frame: Day 1 (Baseline) to Day 16
description: To evaluate the effect of hepatic ultrasound insonification on change from baseline in glucose tolerance and insulin secretion, assessed by an oral glucose tolerance test (OGTT). AUC in this outcome is calculated using the absolute value of insulin measures (compared to incremental AUC below which uses baseline (time 0 insulin) subtracted values).
measure: Change From Baseline in Continuous Glucose Monitoring System (CGMS): Time in Ranges
time frame: 14:00 on Day -1 to 22:00 on Day 1 (Baseline) to 14:00 on Day 15 to 22:00 on Day 16 - omitting data collected between a subject's OGTT glucose consumption start time + 180 minutes
description: To evaluate the effect of hepatic ultrasound insonification on glucose metabolism parameters, assessed by a continuous glucose monitoring system (CGMS)
measure: Change From Baseline in Continuous Glucose Monitoring System (CGMS): Average Daily Glucose
time frame: 14:00 on Day -1 to 22:00 on Day 1 (Baseline) to 14:00 on Day 15 to 22:00 on Day 16 - omitting data collected between a subject's OGTT glucose consumption start time + 180 minutes
description: To evaluate the effect of hepatic ultrasound insonification on glucose metabolism parameters, assessed by a continuous glucose monitoring system (CGMS)
measure: Change From Baseline in Continuous Glucose Monitoring System (CGMS): Blood Glucose Coefficient of Variation
time frame: 14:00 on Day -1 to 22:00 on Day 1 (Baseline) to 14:00 on Day 15 to 22:00 on Day 16 - omitting data collected between a subject's OGTT glucose consumption start time + 180 minutes
description: To evaluate the effect of hepatic ultrasound insonification on glucose metabolism parameters, assessed by a continuous glucose monitoring system (CGMS)
measure: Change From Baseline in Continuous Glucose Monitoring System (CGMS): Low/High Blood Glucose Index
time frame: 14:00 on Day -1 to 22:00 on Day 1 (Baseline) to 14:00 on Day 15 to 22:00 on Day 16 - omitting data collected between a subject's OGTT glucose consumption start time + 180 minutes
description: To evaluate the effect of hepatic ultrasound insonification on glucose metabolism parameters, assessed by a continuous glucose monitoring system (CGMS)
To calculate the LBGI and HBGI, the original BG data for each day/period was to be transformed such that it was centered by zero and bound between -sqrt(10) and sqrt(10).
f(BG,α,β) = [(ln(BG))1.084 - 5.381]*1.509
The transformed values were then to be input into the BG risk function:
r(BG) = 10 * f(BG,α,β)2
The risk of each observation was further to be transformed into two series, risk of low BG series, rl(BG), and risk of high BG series, rh(BG):
rl(BG) = r(BG) if f(BG) < 0 and 0 otherwise rh(BG) = r(BG) if f(BG) > 0 and 0 otherwise These series were then to be averaged to produce the LBGI and the HBGI as shown in the equations in the SAP.
measure: Incidence of Adverse Device Effects (ADEs) With a Severity Score of 2: Treatment Emergent Adverse Events (TEAEs) by System Organ Class and Preferred Term
time frame: Screening to Day 28
description: To evaluate safety and tolerability of hepatic ultrasound insonification in subjects with T2DM. Incidence of adverse device effects included observations of Incidence and severity of clinically significant laboratory abnormalities, Change from baseline in vital signs (blood pressure, temperature, respiratory rate, and heart rate), Incidence and severity of clinical findings on physical examination, Change from baseline in 12-lead electrocardiogram (ECG) parameters; the primary ECG endpoint was QTcF.
To evaluate safety and tolerability of hepatic ultrasound insonification in subjects with T2DM: [Severity Score: 1=Mild; 2=Moderate; 3=Severe; 4=Life-Threatening; 5=Death]
measure: Incidence of Adverse Device Effects (ADEs) With a Severity Score of 3: Treatment Emergent Adverse Events (TEAEs) by System Organ Class and Preferred Term
time frame: Screening to Day 28
description: To evaluate safety and tolerability of hepatic ultrasound insonification in subjects with T2DM. Incidence of adverse device effects included observations of Incidence and severity of clinically significant laboratory abnormalities, Change from baseline in vital signs (blood pressure, temperature, respiratory rate, and heart rate), Incidence and severity of clinical findings on physical examination, Change from baseline in 12-lead electrocardiogram (ECG) parameters; the primary ECG endpoint was QTcF.
To evaluate safety and tolerability of hepatic ultrasound insonification in subjects with T2DM: [Severity Score: 1=Mild; 2=Moderate; 3=Severe; 4=Life-Threatening; 5=Death]
measure: Incidence of Adverse Device Effects (ADEs) With a Severity Score of 4: Treatment Emergent Adverse Events (TEAEs) by System Organ Class and Preferred Term
time frame: Screening to Day 28
description: To evaluate safety and tolerability of hepatic ultrasound insonification in subjects with T2DM. Incidence of adverse device effects included observations of Incidence and severity of clinically significant laboratory abnormalities, Change from baseline in vital signs (blood pressure, temperature, respiratory rate, and heart rate), Incidence and severity of clinical findings on physical examination, Change from baseline in 12-lead electrocardiogram (ECG) parameters; the primary ECG endpoint was QTcF.
To evaluate safety and tolerability of hepatic ultrasound insonification in subjects with T2DM: [Severity Score: 1=Mild; 2=Moderate; 3=Severe; 4=Life-Threatening; 5=Death]
measure: Incidence of Adverse Device Effects (ADEs) With a Severity Score of 5: Treatment Emergent Adverse Events (TEAEs) by System Organ Class and Preferred Term
time frame: Screening to Day 28
description: To evaluate safety and tolerability of hepatic ultrasound insonification in subjects with T2DM. Incidence of adverse device effects included observations of Incidence and severity of clinically significant laboratory abnormalities, Change from baseline in vital signs (blood pressure, temperature, respiratory rate, and heart rate), Incidence and severity of clinical findings on physical examination, Change from baseline in 12-lead electrocardiogram (ECG) parameters; the primary ECG endpoint was QTcF.
To evaluate safety and tolerability of hepatic ultrasound insonification in subjects with T2DM: [Severity Score: 1=Mild; 2=Moderate; 3=Severe; 4=Life-Threatening; 5=Death]
measure: Change From Baseline in Exploratory Biomarkers
time frame: Baseline to Day 18 - Baseline was defined as the last non-missing value collected prior to the first on study hepatic ultrasound insonification
description: To evaluate the effect of hepatic ultrasound insonification on glucose metabolism parameters, as assessed by exploratory markers in blood samples
measure: Change From Baseline in Long-term Glucose Parameters: Fructosamine
time frame: Baseline to Day 18 - Baseline was defined as the last non-missing value collected prior to the first on study hepatic ultrasound insonification
description: To evaluate the effect of hepatic ultrasound insonification on glucose metabolism parameters, as assessed by long-term glucose markers in blood samples
measure: Change From Baseline in Long-term Glucose Parameters: Hemoglobin A1C
time frame: Baseline to Day 18 - Baseline was defined as the last non-missing value collected prior to the first on study hepatic ultrasound insonification
description: To evaluate the effect of hepatic ultrasound insonification on glucose metabolism parameters, as assessed by long-term glucose markers in blood samples
measure: Change From Baseline in Lipid Metabolism Parameters: Cholesterol and Triglycerides
time frame: Baseline to Day 18 - Baseline was defined as the last non-missing value collected prior to the first on study hepatic ultrasound insonification
description: To evaluate the effect of hepatic ultrasound insonification on glucose metabolism parameters, as assessed by lipid metabolism markers in blood samples
measure: Change From Baseline in Lipid Metabolism Parameters: Free Fatty Acids
time frame: Baseline to Day 18 - Baseline was defined as the last non-missing value collected prior to the first on study hepatic ultrasound insonification
description: To evaluate the effect of hepatic ultrasound insonification on glucose metabolism parameters, as assessed by lipid metabolism markers in blood samples
measure: Change From Baseline in Inflammatory Biomarkers: Adiponectin
time frame: Baseline to Day 18 - Baseline was defined as the last non-missing value collected prior to the first on study hepatic ultrasound insonification
description: To evaluate the effect of hepatic ultrasound insonification on glucose metabolism parameters, as assessed by inflammatory biomarkers in blood samples
measure: Change From Baseline in Inflammatory Biomarkers: C Reactive Protein
time frame: Baseline to Day 18 - Baseline was defined as the last non-missing value collected prior to the first on study hepatic ultrasound insonification
description: To evaluate the effect of hepatic ultrasound insonification on glucose metabolism parameters, as assessed by inflammatory biomarkers in blood samples
measure: Change From Baseline in Inflammatory Biomarkers: Interleukin-6
time frame: Baseline to Day 18 - Baseline was defined as the last non-missing value collected prior to the first on study hepatic ultrasound insonification
description: To evaluate the effect of hepatic ultrasound insonification on glucose metabolism parameters, as assessed by inflammatory biomarkers in blood samples
arm group label: Insonification
arm group type: Experimental
description: All subjects enrolled will receive a 3-day, 15 minute per day ultrasound insonification targeting the portis hepatis (liver).
intervention type: Device
intervention name: Hepatic Ultrasound Insonification
description: Hepatic ultrasound insonification will be performed after an overnight fast (no food or drinks except for water for at least 10 hours) at approximately the same time on each day for three days.
arm group label: Insonification
criteria: 
gender: All
minimum age: 21 Years
maximum age: 75 Years
healthy volunteers: No
last name: Bridgette Boggess Franey, MD
role: Principal Investigator
affiliation: ProSciento, Inc.
facility: 
country: United States
url: https://www.dtu.ox.ac.uk/homacalculator/
description: Related Info
citation: Levy JC, Matthews DR, Hermans MP. Correct homeostasis model assessment (HOMA) evaluation uses the computer program. Diabetes Care. 1998 Dec;21(12):2191-2. doi: 10.2337/diacare.21.12.2191. No abstract available.
PMID: 9839117
responsible party type: Sponsor
sharing ipd: No
provided document: 
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
limitations and caveats: The Safety Population consisted of subjects who received hepatic ultrasound insonification and included 16 subjects. The Ultrasound Insonification Effect Population consisted of subjects who received hepatic ultrasound insonification and included 15 subjects. Subject 101-029 had unevaluable data and was excluded from Ultrasound Insonification Effect Population. Subject 101-012 had clamp protocol deviation, and Ultrasound Insonification Effect Population was also analyzed excluding subject.
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