<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/NCT03028571</url>
  </required_header>
  <id_info>
    <org_study_id>150466</org_study_id>
    <nct_id>NCT03028571</nct_id>
  </id_info>
  <brief_title>Autonomic Blockade and Endogenous Glucose Production</brief_title>
  <official_title>Acute Sympathetic Blockade and Endogenous Glucose Production</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Vanderbilt University Medical Center</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Vanderbilt University Medical Center</source>
  <oversight_info>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      The investigators will test the null hypothesis that there will be no changes in the&#xD;
      insulin-mediated suppression of endogenous glucose production (EGP) in response to autonomic&#xD;
      blockade. To test this hypothesis, the investigators propose to determine the role of the&#xD;
      autonomic nervous system in hepatic insulin resistance.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      In this study, the investigators will test the null hypothesis that there will be no changes&#xD;
      in the insulin-mediated suppression of endogenous glucose production (EGP) in response to&#xD;
      autonomic blockade. The investigators will measure EGP at baseline (EGPBsl) and during the&#xD;
      last 30 minutes of a hyperinsulinemic euglycemic clamp (EGPClamp) on two different occasions&#xD;
      (intact and Blocked study days). A double blinded randomize cross-over design will be used.&#xD;
      Subjects will be randomized to either the intact or blocked days and a month later will be&#xD;
      crossed-over to the other arm. The investigator performing the analysis will also be blinded&#xD;
      to the treatments received. At baseline in both study days it is expected to see any&#xD;
      differences since the same subject will serve as his own control. During the clamp, insulin&#xD;
      suppresses EGP. In obese insulin resistant subjects this suppression should be blunted. If&#xD;
      the hypothesis is correct, it is expected an improvement in the suppression by insulin of EGP&#xD;
      during autonomic blockade only. For this study, the primary endpoint therefore, will be the&#xD;
      EGP during the clamp between the intact and blocked days.&#xD;
&#xD;
      H0= {(EGPClamp)Blocked - (EGPClamp)Intact}=0]&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Withdrawn</overall_status>
  <why_stopped>
    The investigators decided not to perform the study. No participants have been enrolled.&#xD;
  </why_stopped>
  <start_date type="Actual">April 17, 2017</start_date>
  <completion_date type="Anticipated">December 31, 2024</completion_date>
  <primary_completion_date type="Anticipated">December 31, 2022</primary_completion_date>
  <phase>Phase 1</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Crossover Assignment</intervention_model>
    <intervention_model_description>Subjects will be studied twice, randomly assigned to star on the intact day (saline) or the blocked day (trimethaphan) and after 1 month cross to the other arm</intervention_model_description>
    <primary_purpose>Basic Science</primary_purpose>
    <masking>Single (Participant)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Endogenous Glucose Production</measure>
    <time_frame>Duration of the study (4 hours)</time_frame>
    <description>Amount of label glucose appearance</description>
  </primary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">0</enrollment>
  <condition>Insulin Resistance</condition>
  <arm_group>
    <arm_group_label>Intact Day</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>The rates of endogenous glucose appearance (Ra) and peripheral glucose uptake (Rd) will be measured during a regular insulin clamp with concomitant infusion of saline at 48 ml/hr IV</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Blocked Day</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>The rates of endogenous glucose appearance (Ra) and peripheral glucose uptake (Rd) will be measured during a regular insulin clamp with concomitant infusion of trimethaphan (4mg/min) IV.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Trimethaphan</intervention_name>
    <description>Trimethaphan 4 mg/min IV will be given as a pharmacological tool to study the role of the autonomic nervous system on the regulation of endogenous glucose production by the liver.</description>
    <arm_group_label>Blocked Day</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Saline</intervention_name>
    <description>IV saline at a rate of 48 mL/hr, will be given during the insulin clamp to resemble the volume infused in the intact day</description>
    <arm_group_label>Intact Day</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Males and females of all races between 18 and 60 years of age&#xD;
&#xD;
          -  Hypertension defined by two or more properly measured seated blood pressure readings&#xD;
             &gt;130/85 mmHg or currently on antihypertensive medication. This will allow us to&#xD;
             include subjects with &quot;pre-hypertension.&quot;&#xD;
&#xD;
          -  Obesity will be defined as having a body mass index (BMI) ≥ 30 kg/m2.&#xD;
&#xD;
          -  Insulin resistance will be defined as a HOMA2 IR index ≥1.6&#xD;
&#xD;
          -  Able and willing to provide informed consent&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Pregnancy or breast feeding&#xD;
&#xD;
          -  Current smokers or history of heavy smoking (&gt;2 packs/day)&#xD;
&#xD;
          -  History of alcohol or drug abuse&#xD;
&#xD;
          -  Previous allergic reaction to study medications&#xD;
&#xD;
          -  Evidence of type I or type II diabetes (i.e. fasting glucose &gt;126 mg/dl, use of&#xD;
             anti-diabetic medications)&#xD;
&#xD;
          -  Cardiovascular disease other than hypertension such as myocardial infarction within 6&#xD;
             months prior to enrollment, presence of angina pectoris, significant arrhythmia,&#xD;
             congestive heart failure (LV hypertrophy acceptable), deep vein thrombosis, pulmonary&#xD;
             embolism, second or third degree heart block, mitral valve stenosis, aortic stenosis,&#xD;
             or hypertrophic cardiomyopathy&#xD;
&#xD;
          -  History of serious cerebrovascular disease such as cerebral hemorrhage, stroke, or&#xD;
             transient ischemic attack&#xD;
&#xD;
          -  History or presence of immunological or hematological disorders&#xD;
&#xD;
          -  Impaired renal function&#xD;
&#xD;
          -  Anemia&#xD;
&#xD;
          -  Treatment with phosphodiesterase 5 inhibitors&#xD;
&#xD;
          -  Treatment with anticoagulants&#xD;
&#xD;
          -  Treatment with chronic systemic glucocorticoid therapy (more than 7 consecutive days&#xD;
             in 1 month)&#xD;
&#xD;
          -  Treatment with any investigational drug in the 1 month preceding the study&#xD;
&#xD;
          -  Inability to give, or withdraw, informed consent&#xD;
&#xD;
          -  Other factors which in the investigator's opinion would prevent the subject from&#xD;
             completing the protocol (i.e., clinically significant abnormalities on clinical,&#xD;
             mental examination or laboratory testing or inability to comply with protocol,&#xD;
             inability to find IV access)&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>60 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Vanderbilt University Medical Center</name>
      <address>
        <city>Nashville</city>
        <state>Tennessee</state>
        <zip>37232</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>June 2021</verification_date>
  <study_first_submitted>January 18, 2017</study_first_submitted>
  <study_first_submitted_qc>January 19, 2017</study_first_submitted_qc>
  <study_first_posted type="Estimate">January 23, 2017</study_first_posted>
  <last_update_submitted>June 3, 2021</last_update_submitted>
  <last_update_submitted_qc>June 3, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">June 8, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Vanderbilt University Medical Center</investigator_affiliation>
    <investigator_full_name>Italo Biaggioni</investigator_full_name>
    <investigator_title>Professor of Medicine and Pharmacology</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Insulin Resistance</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Trimethaphan</mesh_term>
    <mesh_term>Trimethaphan camsylate</mesh_term>
  </intervention_browse>
  <!-- Results have not yet been posted for this study                                          -->
</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/NCT03028571
org study id: 150466
nct id: NCT03028571
lead sponsor: 
is fda regulated drug: Yes
is fda regulated device: No
The investigators will test the null hypothesis that there will be no changes in the
      insulin-mediated suppression of endogenous glucose production (EGP) in response to autonomic
      blockade. To test this hypothesis, the investigators propose to determine the role of the
      autonomic nervous system in hepatic insulin resistance.
In this study, the investigators will test the null hypothesis that there will be no changes
      in the insulin-mediated suppression of endogenous glucose production (EGP) in response to
      autonomic blockade. The investigators will measure EGP at baseline (EGPBsl) and during the
      last 30 minutes of a hyperinsulinemic euglycemic clamp (EGPClamp) on two different occasions
      (intact and Blocked study days). A double blinded randomize cross-over design will be used.
      Subjects will be randomized to either the intact or blocked days and a month later will be
      crossed-over to the other arm. The investigator performing the analysis will also be blinded
      to the treatments received. At baseline in both study days it is expected to see any
      differences since the same subject will serve as his own control. During the clamp, insulin
      suppresses EGP. In obese insulin resistant subjects this suppression should be blunted. If
      the hypothesis is correct, it is expected an improvement in the suppression by insulin of EGP
      during autonomic blockade only. For this study, the primary endpoint therefore, will be the
      EGP during the clamp between the intact and blocked days.

      H0= {(EGPClamp)Blocked - (EGPClamp)Intact}=0]
allocation: Randomized
intervention model: Crossover Assignment
intervention model description: Subjects will be studied twice, randomly assigned to star on the intact day (saline) or the blocked day (trimethaphan) and after 1 month cross to the other arm
primary purpose: Basic Science
masking: Single (Participant)
measure: Endogenous Glucose Production
time frame: Duration of the study (4 hours)
description: Amount of label glucose appearance
arm group label: Intact Day
arm group type: Placebo Comparator
description: The rates of endogenous glucose appearance (Ra) and peripheral glucose uptake (Rd) will be measured during a regular insulin clamp with concomitant infusion of saline at 48 ml/hr IV
arm group label: Blocked Day
arm group type: Experimental
description: The rates of endogenous glucose appearance (Ra) and peripheral glucose uptake (Rd) will be measured during a regular insulin clamp with concomitant infusion of trimethaphan (4mg/min) IV.
intervention type: Drug
intervention name: Trimethaphan
description: Trimethaphan 4 mg/min IV will be given as a pharmacological tool to study the role of the autonomic nervous system on the regulation of endogenous glucose production by the liver.
arm group label: Blocked Day
intervention type: Other
intervention name: Saline
description: IV saline at a rate of 48 mL/hr, will be given during the insulin clamp to resemble the volume infused in the intact day
arm group label: Intact Day
criteria: 
gender: All
minimum age: 18 Years
maximum age: 60 Years
healthy volunteers: No
facility: 
country: United States
responsible party type: Principal Investigator
investigator affiliation: Vanderbilt University Medical Center
investigator full name: Italo Biaggioni
investigator title: Professor of Medicine and Pharmacology
mesh term: Insulin Resistance
mesh term: Trimethaphan
mesh term: Trimethaphan camsylate