Examination of Bromocriptine on Homeostatic and Hedonic Mechanisms of Food Intake in Individuals at High Risk for T2DM

NCT ID: NCT05405244

Last Updated: 2022-09-07

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 55 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-09-19
• Study Completion Date: 2019-09-19

Brief Summary

The current project applies an integrative three-prong approach to investigate the potential of the dopamine D2 receptor (DRD2) agonist bromocriptine to: 1) increase homeostatic satiation signaling, 2) alter neural circuitry to reduce hedonically motivated food intake, and 3) examines a genetic predisposition that may markedly impact the effectiveness of this medication in those at high risk for T2DM.

Detailed Description

Twenty-nine million Americans have diagnosed type 2 diabetes (T2DM), with fewer than half able to meet treatment goals and considerably more are at risk for development of T2DM. Implementation of healthy eating behavior has been identified as a barrier to T2DM treatment and efficacy. The determinants of eating behavior and weight regulation involve a complex interaction among individual-level homeostatic, hedonic, and genetic systems, and the external food environment. The high prevalence of obesity and T2DM suggests hedonic motivation to consume food overrides homeostatic satiation signaling, resulting in excess food intake. Elevated intake increases body mass and promotes T2DM incidence via dysregulation of glucagon-like peptide 1 (GLP-1), amylin, and adiponectin, which in turn can negatively impact T2DM treatment options.

Use of a pharmaceutical, such as bromocriptine, to aid in behavioral change is a novel method for treating and ameliorating T2DM and warrants investigation given that previous work has shown reward response to food images mediates T2DM control. Use of functional magnetic resonance imaging (fMRI) techniques to predict and evaluate hedonically-motivated eating behavior can be used to measure sensitivity to reward, and the role it plays in developing obesity, and is therefore an excellent tool to examine the associations among bromocriptine, satiety hormones, reward sensitivity and eating behavior.

Moreover, since 20-35% of the population carries the DRD2 TaqIA A1 allele, and 65% of the population is overweight or obese and at high risk for T2DM development or currently diagnosed, as much as 23% of the population may greatly benefit from dopamine agonist treatment. Despite the possibility that bromocriptine may have robust impact on T2DM treatment or as prevention therapy in those that are genetically predisposed, few data are available that directly examine the three systems (homeostatic, hedonic, genetic) available to assess whether a genetically-informed, personalized T2DM treatment is viable.

Conditions

Overweight and Obesity; Eating Behavior

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: DIAGNOSTIC
• Blinding Strategy: TRIPLE

Study Groups

Bromocriptine, then Placebo

During the first intervention visit, participants receive a single dose of 1.6mg of bromocriptine (2 0.8mg capsules). Following a 2-week washout period, participants return for the second intervention visit, where they receive 2 capsules of placebo (sugar free calcium supplement) matched in shape (circle) and color (white) to bromocriptine. Both bromocriptine and placebo are administered orally.

Group Type: OTHER

Placebo

Intervention Type: DRUG

2 capsules, orally administered once

Bromocriptine-QR

Intervention Type: DRUG

1.6mg (2 0.8mg capsules), orally administered once

Placebo, then Bromocriptine

During the first intervention visit, participants receive 2 capsules of placebo (sugar free calcium supplement). Following a 2-week washout period, participants return for the second intervention visit, where they receive a single dose of 1.6mg of bromocriptine (2 0.8mg capsules). Both bromocriptine and placebo are administered orally.

Group Type: OTHER

Placebo

Intervention Type: DRUG

2 capsules, orally administered once

Bromocriptine-QR

Intervention Type: DRUG

1.6mg (2 0.8mg capsules), orally administered once

Interventions

Placebo

2 capsules, orally administered once

Intervention Type: DRUG

Bromocriptine-QR

1.6mg (2 0.8mg capsules), orally administered once

Intervention Type: DRUG

Other Intervention Names

placebo (calcium supplement); quick-release (QR) bromocriptine (cycloset)

Eligibility Criteria

Inclusion Criteria

• Baseline BMI between 25 and 35

Exclusion Criteria

• Individuals with current fMRI contraindications (e.g., metal implants, braces)
• Probable current Axis I psychopathology (e.g., major depression disorder, panic disorder, generalized anxiety disorder, bipolar disorder)
• Habitual use of cigarettes or illicit drugs
• Pregnancy or breastfeeding
• Diagnosis of serious medical problems (e.g., diabetes, cardiovascular disease, stroke)
• Current weight loss dieting and/or weight fluctuations great than 10 lbs in the previous 6 weeks
• Do not consume dairy
• Allergy to bromocriptine, dairy, and nuts

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 35 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

American Diabetes Association

OTHER

Sponsor Role: collaborator

University of North Carolina, Chapel Hill

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Kyle S Burger, MPH, RD, PhD

Role: PRINCIPAL_INVESTIGATOR

University of North Carolina, Chapel Hill

Locations

University of North Carolina, Chapel Hill

Chapel Hill, North Carolina, United States

Countries

United States

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

1-17-JDF-031

Identifier Type: OTHER_GRANT

Identifier Source: secondary_id

16-3177

Identifier Type: -

Identifier Source: org_study_id