<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/NCT01714895</url>
  </required_header>
  <id_info>
    <org_study_id>FP7-PEOPLE-2009-IEF #252085-2</org_study_id>
    <secondary_id>Spanish Ministry of Science</secondary_id>
    <nct_id>NCT01714895</nct_id>
  </id_info>
  <brief_title>Effect of Different Plasma Insulin Levels on the Accuracy of Continuous Subcutaneous Glucose Monitoring</brief_title>
  <official_title>New Strategies for Automated Glycaemic Control: the Issue of Continuous Glucose Monitoring Accuracy Under Hypoglycaemic Conditions</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Fundación para la Investigación del Hospital Clínico de Valencia</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Universitat Politècnica de València</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Fundación para la Investigación del Hospital Clínico de Valencia</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Achieving near-normoglycaemia has been established as the main objective for most patients&#xD;
      with diabetes. However, it is well known that intensification of treatment is associated with&#xD;
      an increase in the frequency of hypoglycemia, especially in the context of insulin therapy.&#xD;
      The burden of hypoglycemia in terms of psychological implications, morbidity and even&#xD;
      mortality, explains why it has been defined as the main limiting factor to achievement of&#xD;
      good metabolic control.&#xD;
&#xD;
      Continuous subcutaneous glucose monitoring (CGM) devices have been claimed to be useful in&#xD;
      hypoglycemia detection/prevention, allowing theoretically for safer intensification of&#xD;
      therapy in diabetic patients. However, accuracy of CGM devices, especially in the&#xD;
      hypoglycemic range, raises some concerns. In fact, commercially available CGM devices&#xD;
      estimate plasma glucose from measurements in the interstitial fluid and not in plasma.&#xD;
      However, the relationship between plasma and interstitial glucose is not fully understood,&#xD;
      especially under dynamic conditions, and this may explain the poor CGM performance during&#xD;
      rapid changes in blood glucose and hypoglycemia.&#xD;
&#xD;
      In this project, the relationship between plasma and interstitial glucose will be evaluated&#xD;
      under conditions of normal glucose concentrations and hypoglycemia. Experiments will be&#xD;
      performed to assess the role, if any, of different plasma insulin concentrations on the&#xD;
      accuracy of CGM.&#xD;
&#xD;
      All the information obtained may be relevant to the improvement of the ability of CGM devices&#xD;
      to detect hypoglycemia and hypoglycemic risk.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date>October 2011</start_date>
  <completion_date type="Actual">October 2012</completion_date>
  <primary_completion_date type="Actual">September 2012</primary_completion_date>
  <phase>N/A</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>
    <primary_purpose>Basic Science</primary_purpose>
    <masking>Double (Participant, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Normalized current signal from the CGM devices</measure>
    <time_frame>330 minutes</time_frame>
    <description>CGM devices are electrochemical sensors. Currently available sensors are placed in the subcutaneous tissue where they react with the glucose of the interstitial fluid giving a current signal (in nano Amperes), which is proportional to glucose concentrations. The current signal is then filtered and transformed into plasma glucose estimations through a calibration algorithm built into the CGM device.&#xD;
In this study we will analyze the current signal from CGM obtained under two different experimental conditions:&#xD;
Eu-hypoglycemic clamp with High plasma insulin concentrations&#xD;
Eu-hypoglycemic clamp with relatively Low plasma insulin concentrations&#xD;
This will allow for establishing the role, if any, of different plasma insulin concentrations on the accuracy of CGM to identify plasma glucose falls resulting in hypoglycaemia.&#xD;
Since CGM sensors can exhibit different sensitivities to glucose concentrations, the current signal will be normalized before statistical analysis</description>
  </primary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">14</enrollment>
  <condition>Type 1 Diabetes</condition>
  <condition>Continuous Glucose Monitoring</condition>
  <condition>Hypoglycemia</condition>
  <arm_group>
    <arm_group_label>High plasma insulin-Low plasma insulin</arm_group_label>
    <arm_group_type>Other</arm_group_type>
    <description>Seven out of the 14 subjects recruited in the study have been randomized to receive on the first study day a High insulin glucose clamp and on the second day a Low insulin glucose clamp (sequence 'AB')</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Low plasma insulin-High plasma insulin</arm_group_label>
    <arm_group_type>Other</arm_group_type>
    <description>Seven out of the 14 subjects recruited in the study have been randomized to receive on the first study day a Low insulin glucose clamp and on the second day a High insulin glucose clamp (sequence 'BA')</description>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>High insulin eu-hypoglycemic clamp</intervention_name>
    <description>Primed intravenous insulin infusion at a rate of 1mU/kg/min is given during the whole study duration. Glucose is infused at a variable rate to maintain plasma glucose concentrations 'clamped' at pre-specified levels. Plasma glucose levels will be the same in both study arms.</description>
    <arm_group_label>High plasma insulin-Low plasma insulin</arm_group_label>
    <arm_group_label>Low plasma insulin-High plasma insulin</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Low insulin eu-hypoglycemic clamp</intervention_name>
    <description>Primed intravenous insulin infusion at a rate of 0.3mU/kg/min is given during the whole study duration. Glucose is infused at a variable rate to maintain plasma glucose concentrations 'clamped' at pre-specified levels. Plasma glucose levels will be the same in both study arms.</description>
    <arm_group_label>High plasma insulin-Low plasma insulin</arm_group_label>
    <arm_group_label>Low plasma insulin-High plasma insulin</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Subjects with type 1 diabetes mellitus meeting all of the following criteria will be&#xD;
             considered for admission to the study:&#xD;
&#xD;
               -  Aged between 18 and 60 years&#xD;
&#xD;
               -  Under CSII or MDI treatment for at least six months before Visit 1&#xD;
&#xD;
               -  Body mass index of between 18 and 30 kg/m2&#xD;
&#xD;
               -  HbA1c 6.0-8.5% at Visit 1&#xD;
&#xD;
               -  Normal laboratory values, ECG, and vital signs unless the investigator considered&#xD;
                  an abnormality to be clinically irrelevant&#xD;
&#xD;
               -  Women postmenopausal or using contraception judged by the investigator to be&#xD;
                  adequate (e.g., oral contraceptives, intra-uterine device or surgical treatment)&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Subjects meeting any of the following criteria will not be included in the study:&#xD;
&#xD;
               -  Pregnancy and lactation&#xD;
&#xD;
               -  History of hypersensitivity to the study medications or to drugs with similar&#xD;
                  chemical structures&#xD;
&#xD;
               -  Confirmed hypoglycaemia unawareness&#xD;
&#xD;
               -  Progressive fatal diseases&#xD;
&#xD;
               -  History of drug or alcohol abuse&#xD;
&#xD;
               -  History of positive HIV or hepatitis B or C test&#xD;
&#xD;
               -  Impaired hepatic function, as shown by, but not limited to, SGPT or SGOT of more&#xD;
                  than twice the upper limit of the normal range at visit 1&#xD;
&#xD;
               -  Impaired renal function, as shown by, but not limited to, serum creatinine &gt; 1.5&#xD;
                  mg/dL at visit 1&#xD;
&#xD;
               -  Clinically relevant microvascular, cardiovascular, hepatic, neurologic, endocrine&#xD;
                  or other major systemic diseases other than T1DM which could hinder&#xD;
                  implementation of the clinical study protocol or interpretation of the study&#xD;
                  results&#xD;
&#xD;
               -  Pre-planned surgery during the study&#xD;
&#xD;
               -  Blood donation of more than 500 ml during the past three months for men, or&#xD;
                  during the past six months for women&#xD;
&#xD;
               -  Mental condition rendering the subject unable to understand the nature, scope and&#xD;
                  possible consequences of the study&#xD;
&#xD;
               -  Subject unlikely to comply with clinical study protocol, e.g., uncooperative&#xD;
                  attitude, inability to return for follow-up visits, or poor likelihood of&#xD;
                  completing the study&#xD;
&#xD;
               -  Receipt of an experimental drug or use of an experimental device during the past&#xD;
                  30 days.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>60 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Francisco Javier Ampudia-Blasco, MD, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Hospital Clínico Universitario de Valencia - Fundación INCLIVA</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Servicio de Endocrinología y Nutrición, Hospital Clínico Universitario de Valencia</name>
      <address>
        <city>Valencia</city>
        <zip>46010</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Spain</country>
  </location_countries>
  <verification_date>October 2012</verification_date>
  <study_first_submitted>October 24, 2012</study_first_submitted>
  <study_first_submitted_qc>October 24, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">October 26, 2012</study_first_posted>
  <last_update_submitted>October 24, 2012</last_update_submitted>
  <last_update_submitted_qc>October 24, 2012</last_update_submitted_qc>
  <last_update_posted type="Estimate">October 26, 2012</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Interstitial glucose dynamics</keyword>
  <keyword>Accuracy of continuous glucose monitoring under hypoglycemia</keyword>
  <keyword>Glucose clamp</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Hypoglycemia</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Insulin</mesh_term>
    <mesh_term>Insulin, Globin Zinc</mesh_term>
    <mesh_term>Hypoglycemic Agents</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/NCT01714895
org study id: FP7-PEOPLE-2009-IEF #252085-2
secondary id: Spanish Ministry of Science
nct id: NCT01714895
lead sponsor: 
collaborator: 
has dmc: No
Achieving near-normoglycaemia has been established as the main objective for most patients
      with diabetes. However, it is well known that intensification of treatment is associated with
      an increase in the frequency of hypoglycemia, especially in the context of insulin therapy.
      The burden of hypoglycemia in terms of psychological implications, morbidity and even
      mortality, explains why it has been defined as the main limiting factor to achievement of
      good metabolic control.

      Continuous subcutaneous glucose monitoring (CGM) devices have been claimed to be useful in
      hypoglycemia detection/prevention, allowing theoretically for safer intensification of
      therapy in diabetic patients. However, accuracy of CGM devices, especially in the
      hypoglycemic range, raises some concerns. In fact, commercially available CGM devices
      estimate plasma glucose from measurements in the interstitial fluid and not in plasma.
      However, the relationship between plasma and interstitial glucose is not fully understood,
      especially under dynamic conditions, and this may explain the poor CGM performance during
      rapid changes in blood glucose and hypoglycemia.

      In this project, the relationship between plasma and interstitial glucose will be evaluated
      under conditions of normal glucose concentrations and hypoglycemia. Experiments will be
      performed to assess the role, if any, of different plasma insulin concentrations on the
      accuracy of CGM.

      All the information obtained may be relevant to the improvement of the ability of CGM devices
      to detect hypoglycemia and hypoglycemic risk.
allocation: Randomized
intervention model: Crossover Assignment
primary purpose: Basic Science
masking: Double (Participant, Outcomes Assessor)
measure: Normalized current signal from the CGM devices
time frame: 330 minutes
description: CGM devices are electrochemical sensors. Currently available sensors are placed in the subcutaneous tissue where they react with the glucose of the interstitial fluid giving a current signal (in nano Amperes), which is proportional to glucose concentrations. The current signal is then filtered and transformed into plasma glucose estimations through a calibration algorithm built into the CGM device.
In this study we will analyze the current signal from CGM obtained under two different experimental conditions:
Eu-hypoglycemic clamp with High plasma insulin concentrations
Eu-hypoglycemic clamp with relatively Low plasma insulin concentrations
This will allow for establishing the role, if any, of different plasma insulin concentrations on the accuracy of CGM to identify plasma glucose falls resulting in hypoglycaemia.
Since CGM sensors can exhibit different sensitivities to glucose concentrations, the current signal will be normalized before statistical analysis
arm group label: High plasma insulin-Low plasma insulin
arm group type: Other
description: Seven out of the 14 subjects recruited in the study have been randomized to receive on the first study day a High insulin glucose clamp and on the second day a Low insulin glucose clamp (sequence 'AB')
arm group label: Low plasma insulin-High plasma insulin
arm group type: Other
description: Seven out of the 14 subjects recruited in the study have been randomized to receive on the first study day a Low insulin glucose clamp and on the second day a High insulin glucose clamp (sequence 'BA')
intervention type: Other
intervention name: High insulin eu-hypoglycemic clamp
description: Primed intravenous insulin infusion at a rate of 1mU/kg/min is given during the whole study duration. Glucose is infused at a variable rate to maintain plasma glucose concentrations 'clamped' at pre-specified levels. Plasma glucose levels will be the same in both study arms.
arm group label: High plasma insulin-Low plasma insulin
arm group label: Low plasma insulin-High plasma insulin
intervention type: Other
intervention name: Low insulin eu-hypoglycemic clamp
description: Primed intravenous insulin infusion at a rate of 0.3mU/kg/min is given during the whole study duration. Glucose is infused at a variable rate to maintain plasma glucose concentrations 'clamped' at pre-specified levels. Plasma glucose levels will be the same in both study arms.
arm group label: High plasma insulin-Low plasma insulin
arm group label: Low plasma insulin-High plasma insulin
criteria: 
gender: All
minimum age: 18 Years
maximum age: 60 Years
healthy volunteers: No
last name: Francisco Javier Ampudia-Blasco, MD, PhD
role: Principal Investigator
affiliation: Hospital Clínico Universitario de Valencia - Fundación INCLIVA
facility: 
country: Spain
responsible party type: Sponsor
mesh term: Hypoglycemia
mesh term: Insulin
mesh term: Insulin, Globin Zinc
mesh term: Hypoglycemic Agents