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

NCT05405244 | Completed Phase 3 Results FDA Drug

• 2 other identifiers: 16-31771-17-JDF-031
• Study Type: interventional
• Target: 55
• Locations: 1 country
• Sites: 1

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.

Conditions

Overweight and Obesity; Eating Behavior

Keywords

bromocriptine; dopamine agonist; TaqIA polymorphism; eating behavior; food intake; overweight; obesity

Outcome Measures

Primary Outcomes (3)

• Ad Libitum Food and Beverage Intake (g)

  Ad libitum food intake of highly-palatable snacks is assessed during each intervention arm. Participants are left alone for 25 minutes to eat as much as they want from a selection of snacks (M\&Ms, Skittles, Doritos, cheddar popcorn) and a chocolate milkshake. Both snacks and milkshake are pre- and post-weighed to determine ad libitum food intake.

  Within 15 minutes of completion of the ad libitum period

• Hedonic Ratings of Food as Measured by a Visual Analog Scale

  Testing the effects of the drug on hedonic ratings (pleasantness, desire to consume) of milkshake and snacks on a scale from -100 to 100. Pleasantness was assessed by asking 'How pleasant is this taste?', with responses ranging from -100 (most unpleasant imaginable) to 100 (most pleasant imaginable). Desire to consume was assessed by asking 'How much would you want to eat/drink this?', with responses ranging from -100 (least desirable imaginable) to 100 (most desirable imaginable).

  Up to 5 minutes prior to ad libitum period start

• Change in Voxel-wise Blood Oxygen Level-Dependent (BOLD) Brain Activation in Response to Milkshake Anticipation and Receipt vs. Water

  The fMRI paradigm assesses evoked BOLD response to cue-elicited anticipation and receipt of a milkshake and water. A region-of-interest (ROI) approach is used to assess changes in BOLD signal in the striatum. The striatal response is assessed for the two contrasts of interest: milkshake\>h2o anticipation and milkshake\>h2o receipt. Positive values reflect a higher striatal BOLD activation for the milkshake; negative reflects a higher striatal BOLD activation for the water. Parameter estimates of the relative BOLD response to each of these contrasts are extracted and compared between the two arms. The paradigm has 64 trials and each trial starts with the presentation of a cue for 1s signaling the impending delivery of either 3 mL of highly palatable milkshake or a control water solution over a period of 6s. Taste delivery is followed by a wait period and rinse (tasteless solution). The next trial begins after a 1-9s jitter. Order of milkshake and water trials is pseudo-randomized.

  Baseline and 2 Weeks

Secondary Outcomes (3)

• Ad Libitum Food and Milkshake Intake (g) by TaqIA Allele Status (A1 vs. A2/A2)

  Within 15 minutes of completion of the ad libitum period

• Hedonic Ratings of Milkshake Pleasantness and Desire as Measured by a Visual Analog Scale by TaqIA Allele Status (A1 vs. A2/A2)

  Up to 5 minutes prior to ad libitum period start

• Change in Voxel-wise Blood Oxygen Level-Dependent (BOLD) Brain Activation in Response to Milkshake Anticipation and Receipt vs. Water by TaqIA Allele Status (A1 vs. A2/A2)

  Baseline and 2 Weeks

Study Arms (2)

Bromocriptine, then Placebo

OTHER

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.

Drug: Placebo; Drug: Bromocriptine-QR

Placebo, then Bromocriptine

OTHER

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.

Drug: Placebo; Drug: Bromocriptine-QR

Interventions

Placebo DRUG

2 capsules, orally administered once

Also known as: placebo (calcium supplement)

Bromocriptine, then Placebo; Placebo, then Bromocriptine

Bromocriptine-QR DRUG

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

Also known as: quick-release (QR) bromocriptine (cycloset)

Bromocriptine, then Placebo; Placebo, then Bromocriptine

Eligibility Criteria

• Age: 18 Years - 35 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Baseline BMI between 25 and 35

You may not qualify if:

• 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

Sponsors & Collaborators

• University of North Carolina, Chapel Hill: lead
• American Diabetes Association: collaborator

Study Sites (1)

University of North Carolina, Chapel Hill

Chapel Hill, North Carolina, 27599, United States

Location

MeSH Terms

Conditions

Overweight; Obesity; Feeding Behavior

Interventions

Bromocriptine

Condition Hierarchy (Ancestors)

Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Behavior, Animal; Behavior

Intervention Hierarchy (Ancestors)

Ergotamines; Ergot Alkaloids; Alkaloids; Heterocyclic Compounds; Ergolines; Heterocyclic Compounds, 4 or More Rings; Heterocyclic Compounds, Fused-Ring

Results Point of Contact

• Title: Kyle Burger, PhD, RD, MPH
• Organization: University of North Carolina at Chapel Hill

Kyle_burger@unc.edu

9198439933

Study Officials

• Kyle S Burger, MPH, RD, PhD

  University of North Carolina, Chapel Hill

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: DIAGNOSTIC
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Participants are randomly assigned to one of two possible intervention arms (active drug vs. placebo) at baseline. Following a 2-week washout period, participants receive the other intervention.

Study Record Dates

• First Submitted: May 31, 2022
• First Posted: June 6, 2022
• Study Start: September 19, 2017
• Primary Completion: September 19, 2019
• Study Completion: September 19, 2019
• Last Updated: September 7, 2022
• Results First Posted: August 10, 2022

Record last verified: 2022-05

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ANALYTIC CODE
• Time Frame: beginning 9 and continuing for 36 months following publication
• Access Criteria: Investigator has approved IRB, IEC, or REB and an executed data use/sharing agreement with UNC.

Locations

US (1)