<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/NCT02241603</url>
  </required_header>
  <id_info>
    <org_study_id>CLNB-004-13F</org_study_id>
    <nct_id>NCT02241603</nct_id>
  </id_info>
  <brief_title>Insulin Resistance and Reward</brief_title>
  <acronym>IRRSO</acronym>
  <official_title>Insulin Resistance and Reward Signaling in Obesity</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>VA Office of Research and Development</agency>
      <agency_class>U.S. Fed</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Washington University School of Medicine</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>VA Office of Research and Development</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
    <is_us_export>No</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      Obesity is a common problem in the Veteran population as at least 1 in 3 Veterans are obese.&#xD;
      When obese people eat food they have less response in areas of the brain that sense pleasure&#xD;
      (reward). Decreased pleasure response to food predicts future weight gain. It is not known if&#xD;
      this poor brain response is reversible or why obese people's brains respond this way. Insulin&#xD;
      in the brain regulates the brain's sensing of pleasure. As people gain weight the function of&#xD;
      insulin becomes impaired. The investigators will study if impaired function of insulin is&#xD;
      related to a poor brain response to food and if this brain response predicts voluntary intake&#xD;
      of food and response to a diet. The investigators will also study if improving the function&#xD;
      of insulin with weight loss improves the brain response. These studies will improve the&#xD;
      understanding as to why weight loss is difficult and inform us if improving insulin signaling&#xD;
      is a potential way to treat obesity.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The current research proposal will investigate the relationship of insulin sensitivity to&#xD;
      brain reward signaling. In most obese individuals, insulin signaling is impaired (insulin&#xD;
      resistance). Preclinical animal studies suggest that insulin resistance in brain regions&#xD;
      important for reward contribute to overeating. This proposal aims to test these hypotheses in&#xD;
      humans and to determine if these characteristics are pertinent to clinical outcomes (food&#xD;
      intake and weight loss). In humans increased body mass index (BMI) and weight gain occur with&#xD;
      decreased food consumption-induced neural activation (consummatory reward) in the caudate of&#xD;
      the dorsal striatum. It has been speculated that diminished consummatory reward causes&#xD;
      overeating and prevents weight loss, however, this hypothesis has not been directly tested.&#xD;
      Further, mechanisms for impaired food consumption-induced neural activation in obesity have&#xD;
      not been investigated.&#xD;
&#xD;
      The primary research outcomes of the proposed study are: 1) insulin sensitivity determined by&#xD;
      hyperinsulinemic euglycemic clamp, 2) food consumption-induced neural activation as&#xD;
      determined by blood-oxygen dependent functional magnetic resonance imaging (BOLD fMRI)&#xD;
      scanning, 3) caloric intake at a buffet meal, and 4) weight loss during a weight loss&#xD;
      intervention. Based on screening and baseline outcome assessments half of participants will&#xD;
      be enrolled in a weight loss intervention and then repeat outcomes measures after&#xD;
      intervention. Others will only complete baseline outcome measures. Secondary measures of the&#xD;
      study include whole brain activation analyses, neuroendocrine hormone measurement at the time&#xD;
      of imaging, psychometric measures including eating behaviors and personality characteristics,&#xD;
      and measures of reward sensitivity.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">November 17, 2014</start_date>
  <completion_date type="Actual">July 1, 2020</completion_date>
  <primary_completion_date type="Actual">July 1, 2020</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Non-Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <intervention_model_description>Participants are assigned to two groups in parallel for the duration of the study. There is a dietary weight loss intervention aiming for ~5-10% weight loss</intervention_model_description>
    <primary_purpose>Other</primary_purpose>
    <masking>Single (Participant)</masking>
    <masking_description>participants are expressly assigned to intervention groups through a non-random method based on metabolic testing</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>food consumption-induced neural activation</measure>
    <time_frame>~4-9months</time_frame>
    <description>food consumption-induced neural activation as determined by blood-oxygen dependent functional magnetic resonance imaging (BOLD fMRI) scanning</description>
  </primary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">59</enrollment>
  <condition>Obesity</condition>
  <arm_group>
    <arm_group_label>Weight loss</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Obese Veterans will aim to lose 5-10% body weight</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Baseline comparator</arm_group_label>
    <arm_group_type>No Intervention</arm_group_type>
    <description>Obese Veterans similar to Aim 1 in BMI, age, gender but not insulin sensitivity will not undergo weight loss</description>
  </arm_group>
  <intervention>
    <intervention_type>Behavioral</intervention_type>
    <intervention_name>Weight loss</intervention_name>
    <description>Obese Veterans will undergo dietary education for weight loss or weight maintenance</description>
    <arm_group_label>Weight loss</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Age 25-60yoa, inclusive.&#xD;
&#xD;
          -  BMI 30.0 and 45.0 kg/m2, inclusive.&#xD;
&#xD;
          -  Normal visual acuity with correction.&#xD;
&#xD;
          -  Able to travel regularly to the St. Louis VA and Washington University for research&#xD;
             visits.&#xD;
&#xD;
          -  Completed signed informed consent form.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Current or history of significant psychiatric disease, including Binge Eating Disorder&#xD;
             (BED).&#xD;
&#xD;
          -  Current or history of significant substance abuse or extended use of tobacco.&#xD;
&#xD;
          -  Contraindications for MRI (e.g., pregnancy, claustrophobia, pacemaker, circumference &gt;&#xD;
             54 inches, weight &gt; 400 lbs, etc.);&#xD;
&#xD;
          -  Significant cardiovascular, pulmonary, renal, liver, neurologic, or metabolic disease.&#xD;
&#xD;
          -  Diabetes mellitus.&#xD;
&#xD;
          -  Significant anemia.&#xD;
&#xD;
          -  Treatment with a medication the affects insulin sensitivity.&#xD;
&#xD;
          -  Treatment with centrally acting medications.&#xD;
&#xD;
          -  Frequent shift work.&#xD;
&#xD;
          -  Significant in-mobility or unable to lay on back still for 1 hour.&#xD;
&#xD;
          -  History of bariatric surgery.&#xD;
&#xD;
          -  Food allergies/ intolerance that would prevent completing study.&#xD;
&#xD;
          -  Symptoms concerning for untreated active mental health disease&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>25 Years</minimum_age>
    <maximum_age>60 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Julia P Dunn, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>St. Louis VA Medical Center John Cochran Division, St. Louis, MO</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>St. Louis VA Medical Center John Cochran Division, St. Louis, MO</name>
      <address>
        <city>Saint Louis</city>
        <state>Missouri</state>
        <zip>63106</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>July 2020</verification_date>
  <study_first_submitted>September 11, 2014</study_first_submitted>
  <study_first_submitted_qc>September 11, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 16, 2014</study_first_posted>
  <last_update_submitted>July 7, 2020</last_update_submitted>
  <last_update_submitted_qc>July 7, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">July 8, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Insulin resistance</keyword>
  <keyword>Consummatory Reward</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Obesity</mesh_term>
    <mesh_term>Insulin Resistance</mesh_term>
  </condition_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/NCT02241603
org study id: CLNB-004-13F
nct id: NCT02241603
lead sponsor: 
collaborator: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
is us export: No
Obesity is a common problem in the Veteran population as at least 1 in 3 Veterans are obese.
      When obese people eat food they have less response in areas of the brain that sense pleasure
      (reward). Decreased pleasure response to food predicts future weight gain. It is not known if
      this poor brain response is reversible or why obese people's brains respond this way. Insulin
      in the brain regulates the brain's sensing of pleasure. As people gain weight the function of
      insulin becomes impaired. The investigators will study if impaired function of insulin is
      related to a poor brain response to food and if this brain response predicts voluntary intake
      of food and response to a diet. The investigators will also study if improving the function
      of insulin with weight loss improves the brain response. These studies will improve the
      understanding as to why weight loss is difficult and inform us if improving insulin signaling
      is a potential way to treat obesity.
The current research proposal will investigate the relationship of insulin sensitivity to
      brain reward signaling. In most obese individuals, insulin signaling is impaired (insulin
      resistance). Preclinical animal studies suggest that insulin resistance in brain regions
      important for reward contribute to overeating. This proposal aims to test these hypotheses in
      humans and to determine if these characteristics are pertinent to clinical outcomes (food
      intake and weight loss). In humans increased body mass index (BMI) and weight gain occur with
      decreased food consumption-induced neural activation (consummatory reward) in the caudate of
      the dorsal striatum. It has been speculated that diminished consummatory reward causes
      overeating and prevents weight loss, however, this hypothesis has not been directly tested.
      Further, mechanisms for impaired food consumption-induced neural activation in obesity have
      not been investigated.

      The primary research outcomes of the proposed study are: 1) insulin sensitivity determined by
      hyperinsulinemic euglycemic clamp, 2) food consumption-induced neural activation as
      determined by blood-oxygen dependent functional magnetic resonance imaging (BOLD fMRI)
      scanning, 3) caloric intake at a buffet meal, and 4) weight loss during a weight loss
      intervention. Based on screening and baseline outcome assessments half of participants will
      be enrolled in a weight loss intervention and then repeat outcomes measures after
      intervention. Others will only complete baseline outcome measures. Secondary measures of the
      study include whole brain activation analyses, neuroendocrine hormone measurement at the time
      of imaging, psychometric measures including eating behaviors and personality characteristics,
      and measures of reward sensitivity.
allocation: Non-Randomized
intervention model: Parallel Assignment
intervention model description: Participants are assigned to two groups in parallel for the duration of the study. There is a dietary weight loss intervention aiming for ~5-10% weight loss
primary purpose: Other
masking: Single (Participant)
masking description: participants are expressly assigned to intervention groups through a non-random method based on metabolic testing
measure: food consumption-induced neural activation
time frame: ~4-9months
description: food consumption-induced neural activation as determined by blood-oxygen dependent functional magnetic resonance imaging (BOLD fMRI) scanning
arm group label: Weight loss
arm group type: Experimental
description: Obese Veterans will aim to lose 5-10% body weight
arm group label: Baseline comparator
arm group type: No Intervention
description: Obese Veterans similar to Aim 1 in BMI, age, gender but not insulin sensitivity will not undergo weight loss
intervention type: Behavioral
intervention name: Weight loss
description: Obese Veterans will undergo dietary education for weight loss or weight maintenance
arm group label: Weight loss
criteria: 
gender: All
minimum age: 25 Years
maximum age: 60 Years
healthy volunteers: No
last name: Julia P Dunn, MD
role: Principal Investigator
affiliation: St. Louis VA Medical Center John Cochran Division, St. Louis, MO
facility: 
country: United States
responsible party type: Sponsor
mesh term: Obesity
mesh term: Insulin Resistance
sharing ipd: No