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Insulin Resistance and Reward (IRRSO)

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ClinicalTrials.gov Identifier: NCT02241603
Recruitment Status : Recruiting
First Posted : September 16, 2014
Last Update Posted : December 12, 2017
Sponsor:
Collaborator:
Washington University School of Medicine
Information provided by (Responsible Party):
VA Office of Research and Development

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Obesity Behavioral: Weight loss Phase 2

Detailed Description:

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.


Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 80 participants
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
Masking: Single (Participant)
Masking Description: participants are expressly assigned to intervention groups through a non-random method based on metabolic testing
Primary Purpose: Other
Official Title: Insulin Resistance and Reward Signaling in Obesity
Actual Study Start Date : November 17, 2014
Estimated Primary Completion Date : December 31, 2018
Estimated Study Completion Date : December 31, 2019

Resource links provided by the National Library of Medicine

U.S. FDA Resources

Arm Intervention/treatment
Experimental: Weight loss
Obese Veterans will aim to lose 5-10% body weight
Behavioral: Weight loss
Obese Veterans will undergo dietary education for weight loss or weight maintenance
No Intervention: Baseline comparator
Obese Veterans similar to Aim 1 in BMI, age, gender but not insulin sensitivity will not undergo weight loss



Primary Outcome Measures :
  1. food consumption-induced neural activation [ Time Frame: ~4-9months ]
    food consumption-induced neural activation as determined by blood-oxygen dependent functional magnetic resonance imaging (BOLD fMRI) scanning



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Ages Eligible for Study:   25 Years to 60 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Age 25-60yoa, inclusive.
  • BMI 30.0 and 45.0 kg/m2, inclusive.
  • Normal visual acuity with correction.
  • Able to travel regularly to the St. Louis VA and Washington University for research visits.
  • Completed signed informed consent form.

Exclusion Criteria:

  • Current or history of significant psychiatric disease, including Binge Eating Disorder (BED).
  • Current or history of significant substance abuse or extended use of tobacco.
  • Contraindications for MRI (e.g., pregnancy, claustrophobia, pacemaker, circumference > 54 inches, weight > 400 lbs, etc.);
  • Significant cardiovascular, pulmonary, renal, liver, neurologic, or metabolic disease.
  • Diabetes mellitus.
  • Significant anemia.
  • Treatment with a medication the affects insulin sensitivity.
  • Treatment with centrally acting medications.
  • Frequent shift work.
  • Significant in-mobility or unable to lay on back still for 1 hour.
  • History of bariatric surgery.
  • Food allergies/ intolerance that would prevent completing study.
  • Symptoms concerning for untreated active mental health disease

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02241603


Contacts
Contact: Julia P Dunn, MD julia.dunn@va.gov

Locations
United States, Missouri
St. Louis VA Medical Center John Cochran Division, St. Louis, MO Recruiting
Saint Louis, Missouri, United States, 63106
Contact: Julia P Dunn, MD       julia.dunn@va.gov   
Principal Investigator: Julia P Dunn, MD         
Sponsors and Collaborators
VA Office of Research and Development
Washington University School of Medicine
Investigators
Principal Investigator: Julia P Dunn, MD St. Louis VA Medical Center John Cochran Division, St. Louis, MO

Responsible Party: VA Office of Research and Development
ClinicalTrials.gov Identifier: NCT02241603     History of Changes
Other Study ID Numbers: CLNB-004-13F
First Posted: September 16, 2014    Key Record Dates
Last Update Posted: December 12, 2017
Last Verified: December 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No

Keywords provided by VA Office of Research and Development:
Insulin resistance
Consummatory Reward

Additional relevant MeSH terms:
Obesity
Insulin Resistance
Overnutrition
Nutrition Disorders
Overweight
Body Weight
Signs and Symptoms
Hyperinsulinism
Glucose Metabolism Disorders
Metabolic Diseases
Insulin, Globin Zinc
Insulin
Hypoglycemic Agents
Physiological Effects of Drugs