Insulin Resistance and Reward Signaling in Obesity

NCT02241603 | Completed Phase 1 DMC

• 1 other identifier: CLNB-004-13F
• Study Type: interventional
• Target: 37
• Locations: 1 country
• Sites: 1

Brief Summary

Obesity is a common problem in the Veteran population as at least 1 in 3 Veterans have obesity. When people with obesity taste 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 lessened brain response to food and if this brain response predicts voluntary intake of food and response to a low-calorie 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.

Conditions

Obesity

Keywords

Insulin resistance; Consummatory Reward

Outcome Measures

Primary Outcomes (1)

• food consumption-induced neural activation

  food consumption-induced neural activation as determined by blood-oxygen dependent functional magnetic resonance imaging (BOLD fMRI) scanning

  ~4-9months

Study Arms (2)

MUO (metabolically unhealthy)

EXPERIMENTAL

Veterans with obesity and determined metabolically unhealthy, weight stable before attempting to lose 5-10% body weight with caloric restriction intervention Weight loss completers through dietary education for caloric restriction to lose 5-10% of body weight.

Behavioral: Weight loss

MHO (metabolically healthy)

NO INTERVENTION

Veterans with obesity determined to be metabolically healthy and weight stable

Interventions

Weight loss BEHAVIORAL

Veterans with obesity who are metabolically unhealthy will undergo dietary intervention aiming for 5-10% weight loss

MUO (metabolically unhealthy)

Eligibility Criteria

• Age: 25 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• VA Office of Research and Development: lead
• Washington University School of Medicine: collaborator

Study Sites (1)

St. Louis VA Medical Center John Cochran Division, St. Louis, MO

St Louis, Missouri, 63106, United States

Location

Related Publications (1)

• Dunn JP, Lamichhane B, Smith GI, Garner A, Wallendorf M, Hershey T, Klein S. Dorsal striatal response to taste is modified by obesity and insulin resistance. Obesity (Silver Spring). 2023 Aug;31(8):2065-2075. doi: 10.1002/oby.23799.

  PMID: 37475685 RESULT

MeSH Terms

Conditions

Obesity; Insulin Resistance

Condition Hierarchy (Ancestors)

Overweight; Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Hyperinsulinism; Glucose Metabolism Disorders; Metabolic Diseases

Study Officials

• Julia P Dunn, MD

  St. Louis VA Medical Center John Cochran Division, St. Louis, MO

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Masking Details: participants are expressly assigned to intervention groups through a non-random method based on metabolic testing
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: FED
• Responsible Party: SPONSOR

Model Details: Participants are assigned to two groups in parallel based on baseline metabolic laboratory screening. One group was to complete dietary weight loss intervention aiming for \~5-10% weight loss

Study Record Dates

• First Submitted: September 11, 2014
• First Posted: September 16, 2014
• Study Start: November 17, 2014
• Primary Completion: July 1, 2020
• Study Completion: July 6, 2020
• Last Updated: May 12, 2026

Record last verified: 2026-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)