<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/NCT02982551</url>
  </required_header>
  <id_info>
    <org_study_id>PRO15040502</org_study_id>
    <nct_id>NCT02982551</nct_id>
  </id_info>
  <brief_title>Insulin Modulation of fMRI Connectivity in Healthy Adults</brief_title>
  <official_title>Insulin Modulation of fMRI Connectivity and Food Reward</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Pittsburgh</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University of Pittsburgh</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      This study evaluates the effects of changing insulin levels on brain activity. Participants&#xD;
      will complete functional magnetic resonance imaging (fMRI) scans during fasting conditions,&#xD;
      then during an insulin infusion.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Insulin is a hormone released by the pancreas in response to increases in glucose levels that&#xD;
      result from food intake. In addition to stimulating glucose uptake in the periphery, insulin&#xD;
      signals the central nervous system to induce satiety and inhibit feeding behavior.&#xD;
&#xD;
      To begin to identify the specific effects of circulating insulin on brain networks, the&#xD;
      current study will recruit healthy participants who will undergo two functional magnetic&#xD;
      resonance imaging scans. One scan will be performed in the fasted state, and the alternate&#xD;
      scan will be conducted during an isoglycemic hyperinsulinemic clamp.&#xD;
&#xD;
      This project will allow us to identify the specific effects of circulating insulin on brain&#xD;
      reactivity to palatable food.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Withdrawn</overall_status>
  <why_stopped>
    Principal Investigator Departed University&#xD;
  </why_stopped>
  <start_date type="Actual">January 1, 2016</start_date>
  <completion_date type="Actual">December 2017</completion_date>
  <primary_completion_date type="Anticipated">December 2017</primary_completion_date>
  <phase>Early Phase 1</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>Basic Science</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>fMRI BOLD Response in Brain</measure>
    <time_frame>During Taste Task in fMRI Scanner. Task Duration is approximately 14 minutes.</time_frame>
    <description>The investigators will monitor the blood oxygen level dependent response using fMRI and compare activation during &quot;taste&quot; trials vs. &quot;no taste&quot; trials.</description>
  </primary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">0</enrollment>
  <condition>Healthy Volunteers</condition>
  <arm_group>
    <arm_group_label>Hyperinsulinemic Clamp</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants will complete two MRI scans approximately one hour apart - one under baseline conditions and the second during an insulin infusion. Each scan will include data collected during rest, and a taste task. The taste task involves receiving milkshake or a tasteless solution. After the first scan, an isoglycemic-hyperinsulinemic clamp will be implemented. An IV will be placed in the antecubital vein of of arm for infusion of insulin and dextrose. HumuLIN®-R regular insulin will be infused at 40 mU/m2/min. A second IV will be inserted in the back of the hand on the opposite arm to allow for frequent sampling of blood glucose levels. Dextrose infusion will be used to keep the blood sugar level within 5mg/dl of the baseline value. The study team will monitor blood glucose levels and adjust dextrose infusions as necessary. Thirty minutes after starting the insulin infusion, participants will be moved back into the bore of the MRI scanner for the repeat scans.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Insulin</intervention_name>
    <description>Insulin will be administered peripherally to observe the effects of circulating insulin on brain activity</description>
    <arm_group_label>Hyperinsulinemic Clamp</arm_group_label>
    <other_name>HumuLIN®-R</other_name>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Taste Task</intervention_name>
    <description>Participants will taste milkshakes and a tasteless solution to observe the brain responses to palatable taste.</description>
    <arm_group_label>Hyperinsulinemic Clamp</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Magnetic Resonance Imaging</intervention_name>
    <description>Participants will complete two MRI scans approximately 60 minutes apart - one under baseline fasting conditions and the second during isoglycemic-hyperinsulinemia. Each functional scan will include a resting-state BOLD sequence followed by a taste-reward task. Functional MRI sequences will last approximately 30 minutes. MRI scanning will also include approximately 30 minutes of structural MRI scans.</description>
    <arm_group_label>Hyperinsulinemic Clamp</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Dextrose</intervention_name>
    <description>During hyperinsulinemic clamp, participants will be infused with a variable rate dextrose infusion will be used to keep the blood sugar level within 5mg/dl of the baseline glucose value.</description>
    <arm_group_label>Hyperinsulinemic Clamp</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Body mass index between 18 and 24&#xD;
&#xD;
          -  HOMA-IR &lt; 1.55 (homeostatic model assessment of insulin resistance - ((glucose x&#xD;
             insulin) / 405)).&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Current or lifetime history of any cardiovascular disease or surgery (including&#xD;
             hypertension, stroke, myocardial infarction, congestive heart failure, atrial or&#xD;
             ventricular arrhythmias, coronary bypass, carotid artery, or peripheral vascular&#xD;
             surgery)&#xD;
&#xD;
          -  Current or lifetime history of cancer, a chronic kidney or liver condition, type I or&#xD;
             II diabetes, or any pulmonary or respiratory disease&#xD;
&#xD;
          -  Current or lifetime diagnoses of any substance abuse&#xD;
&#xD;
          -  Positive urine drug screen&#xD;
&#xD;
          -  Current or lifetime use of glucocorticoid medications for &gt;1 month&#xD;
&#xD;
          -  A previous cerebrovascular accident or trauma involving loss of consciousness&#xD;
&#xD;
          -  Previous neurosurgery or history of a neurological condition&#xD;
&#xD;
          -  Pregnancy (females)&#xD;
&#xD;
          -  Claustrophobia&#xD;
&#xD;
          -  Ferrous metallic implants or any surgically placed medical device not cleared for&#xD;
             safety at 3Tesla MRI strength&#xD;
&#xD;
          -  Peripheral vascular disease&#xD;
&#xD;
          -  Liver, kidney, or active blood disease&#xD;
&#xD;
          -  Peripheral neuropathy&#xD;
&#xD;
          -  Anemia (hematocrit &lt;34%)&#xD;
&#xD;
          -  Inability and/or willingness to comply with the protocol as written&#xD;
&#xD;
          -  Fasting glucose &gt; 126 mg/dL&#xD;
&#xD;
          -  Currently taking blood thinners such as coumadin, Lovenox, etc.&#xD;
&#xD;
          -  Currently taking any medications that can alter glucose homeostasis (steroids,&#xD;
             glucocorticoids, nicotinic acid)&#xD;
&#xD;
          -  Current use of any psychotropic medications (SSRI, SNRI, etc.)&#xD;
&#xD;
          -  Currently taking thiazolidinediones or insulin&#xD;
&#xD;
          -  Currently use of statins or anti-hypertensive medications&#xD;
&#xD;
          -  Use of medications related to HIV that can affect insulin sensitivity. We will NOT&#xD;
             specifically test for HIV serostatus.&#xD;
&#xD;
          -  Females currently on hormone replacement therapy (HRT) less than 6 months&#xD;
&#xD;
          -  Participants will be instructed to abstain from eating, drinking (other than water),&#xD;
             smoking and exercise for the 12 hours prior to each study visit.&#xD;
&#xD;
          -  Being left handed&#xD;
&#xD;
          -  Body mass index above 24 or below 18&#xD;
&#xD;
          -  Milk allergy / lactose intolerance&#xD;
&#xD;
          -  Polycystic ovary syndrome&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>21 Years</minimum_age>
    <maximum_age>30 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>John P Ryan, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Pittsburgh</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Western Psychiatric Institute and Clinic</name>
      <address>
        <city>Pittsburgh</city>
        <state>Pennsylvania</state>
        <zip>15213</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>November 2017</verification_date>
  <study_first_submitted>November 22, 2016</study_first_submitted>
  <study_first_submitted_qc>November 30, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">December 5, 2016</study_first_posted>
  <last_update_submitted>November 30, 2017</last_update_submitted>
  <last_update_submitted_qc>November 30, 2017</last_update_submitted_qc>
  <last_update_posted type="Actual">December 4, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>University of Pittsburgh</investigator_affiliation>
    <investigator_full_name>John Patrick Ryan</investigator_full_name>
    <investigator_title>PhD</investigator_title>
  </responsible_party>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Insulin</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- 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/NCT02982551
org study id: PRO15040502
nct id: NCT02982551
lead sponsor: 
has dmc: No
This study evaluates the effects of changing insulin levels on brain activity. Participants
      will complete functional magnetic resonance imaging (fMRI) scans during fasting conditions,
      then during an insulin infusion.
Insulin is a hormone released by the pancreas in response to increases in glucose levels that
      result from food intake. In addition to stimulating glucose uptake in the periphery, insulin
      signals the central nervous system to induce satiety and inhibit feeding behavior.

      To begin to identify the specific effects of circulating insulin on brain networks, the
      current study will recruit healthy participants who will undergo two functional magnetic
      resonance imaging scans. One scan will be performed in the fasted state, and the alternate
      scan will be conducted during an isoglycemic hyperinsulinemic clamp.

      This project will allow us to identify the specific effects of circulating insulin on brain
      reactivity to palatable food.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Basic Science
masking: None (Open Label)
measure: fMRI BOLD Response in Brain
time frame: During Taste Task in fMRI Scanner. Task Duration is approximately 14 minutes.
description: The investigators will monitor the blood oxygen level dependent response using fMRI and compare activation during "taste" trials vs. "no taste" trials.
arm group label: Hyperinsulinemic Clamp
arm group type: Experimental
description: Participants will complete two MRI scans approximately one hour apart - one under baseline conditions and the second during an insulin infusion. Each scan will include data collected during rest, and a taste task. The taste task involves receiving milkshake or a tasteless solution. After the first scan, an isoglycemic-hyperinsulinemic clamp will be implemented. An IV will be placed in the antecubital vein of of arm for infusion of insulin and dextrose. HumuLIN®-R regular insulin will be infused at 40 mU/m2/min. A second IV will be inserted in the back of the hand on the opposite arm to allow for frequent sampling of blood glucose levels. Dextrose infusion will be used to keep the blood sugar level within 5mg/dl of the baseline value. The study team will monitor blood glucose levels and adjust dextrose infusions as necessary. Thirty minutes after starting the insulin infusion, participants will be moved back into the bore of the MRI scanner for the repeat scans.
intervention type: Drug
intervention name: Insulin
description: Insulin will be administered peripherally to observe the effects of circulating insulin on brain activity
arm group label: Hyperinsulinemic Clamp
other name: HumuLIN®-R
intervention type: Other
intervention name: Taste Task
description: Participants will taste milkshakes and a tasteless solution to observe the brain responses to palatable taste.
arm group label: Hyperinsulinemic Clamp
intervention type: Other
intervention name: Magnetic Resonance Imaging
description: Participants will complete two MRI scans approximately 60 minutes apart - one under baseline fasting conditions and the second during isoglycemic-hyperinsulinemia. Each functional scan will include a resting-state BOLD sequence followed by a taste-reward task. Functional MRI sequences will last approximately 30 minutes. MRI scanning will also include approximately 30 minutes of structural MRI scans.
arm group label: Hyperinsulinemic Clamp
intervention type: Drug
intervention name: Dextrose
description: During hyperinsulinemic clamp, participants will be infused with a variable rate dextrose infusion will be used to keep the blood sugar level within 5mg/dl of the baseline glucose value.
arm group label: Hyperinsulinemic Clamp
criteria: 
gender: All
minimum age: 21 Years
maximum age: 30 Years
healthy volunteers: Accepts Healthy Volunteers
last name: John P Ryan, PhD
role: Principal Investigator
affiliation: University of Pittsburgh
facility: 
country: United States
responsible party type: Principal Investigator
investigator affiliation: University of Pittsburgh
investigator full name: John Patrick Ryan
investigator title: PhD
mesh term: Insulin
sharing ipd: No