Examination of Bromocriptine on Homeostatic and Hedonic Mechanisms of Food Intake in Individuals at High Risk for T2DM
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| ClinicalTrials.gov Identifier: NCT05405244 |
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Recruitment Status :
Completed
First Posted : June 6, 2022
Results First Posted : August 10, 2022
Last Update Posted : September 7, 2022
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| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Overweight and Obesity Eating Behavior | Drug: Placebo Drug: Bromocriptine-QR | Phase 3 |
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.
| Study Type : | Interventional (Clinical Trial) |
| Actual Enrollment : | 55 participants |
| Allocation: | Randomized |
| Intervention Model: | Crossover Assignment |
| Intervention Model Description: | 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. |
| Masking: | Triple (Participant, Investigator, Outcomes Assessor) |
| Primary Purpose: | Diagnostic |
| Official Title: | A Multimodel Examination of Bromocriptine on Homeostatic and Hedonic Mechanisms of Food Intake in Individuals at High Risk for Type 2 Diabetes |
| Actual Study Start Date : | September 19, 2017 |
| Actual Primary Completion Date : | September 19, 2019 |
| Actual Study Completion Date : | September 19, 2019 |
| Arm | Intervention/treatment |
|---|---|
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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.
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Drug: Placebo
2 capsules, orally administered once
Other Name: placebo (calcium supplement) Drug: Bromocriptine-QR 1.6mg (2 0.8mg capsules), orally administered once
Other Name: quick-release (QR) bromocriptine (cycloset) |
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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.
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Drug: Placebo
2 capsules, orally administered once
Other Name: placebo (calcium supplement) Drug: Bromocriptine-QR 1.6mg (2 0.8mg capsules), orally administered once
Other Name: quick-release (QR) bromocriptine (cycloset) |
- Ad Libitum Food and Beverage Intake (g) [ Time Frame: Within 15 minutes of completion of the ad libitum period ]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.
- Hedonic Ratings of Food as Measured by a Visual Analog Scale [ Time Frame: Up to 5 minutes prior to ad libitum period start ]
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).
- Change in Voxel-wise Blood Oxygen Level-Dependent (BOLD) Brain Activation in Response to Milkshake Anticipation and Receipt vs. Water [ Time Frame: Baseline and 2 Weeks ]
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.
- Ad Libitum Food and Milkshake Intake (g) by TaqIA Allele Status (A1 vs. A2/A2) [ Time Frame: Within 15 minutes of completion of the ad libitum period ]Testing the drug by gene (TaqIA) interaction on ad libitum food intake (g).The presence of the high-risk A1 allele of the TaqIA polymorphism (rs1800497) in the DRD2 gene was determined from saliva samples and is compared to the A2/A2 variant.
- Hedonic Ratings of Milkshake Pleasantness and Desire as Measured by a Visual Analog Scale by TaqIA Allele Status (A1 vs. A2/A2) [ Time Frame: Up to 5 minutes prior to ad libitum period start ]
Testing the drug by gene (TaqIA) interaction on hedonic ratings (pleasantness, desire to consume) of milkshake on a scale from -100 to 100. Testing the drug by gene (TaqIA) interaction on ad libitum milkshake (g). The presence of the high-risk A1 allele of the TaqIA polymorphism (rs1800497) in the DRD2 gene was determined from saliva samples and is compared to the A2/A2 variant.
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).
- 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) [ Time Frame: Baseline and 2 Weeks ]
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 these contrasts are extracted and used to test the drug by gene (TaqIA) interaction.
The paradigm has 64 trials and each trial starts with the presentation of a cue signaling the impending delivery of either 3 mL of highly palatable milkshake or a control water solution over a 6s period. 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.
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| Ages Eligible for Study: | 18 Years to 35 Years (Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | Yes |
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
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): NCT05405244
| United States, North Carolina | |
| University of North Carolina, Chapel Hill | |
| Chapel Hill, North Carolina, United States, 27599 | |
| Principal Investigator: | Kyle S Burger, MPH, RD, PhD | University of North Carolina, Chapel Hill |
Documents provided by University of North Carolina, Chapel Hill:
| Responsible Party: | University of North Carolina, Chapel Hill |
| ClinicalTrials.gov Identifier: | NCT05405244 |
| Other Study ID Numbers: |
16-3177 1-17-JDF-031 ( Other Grant/Funding Number: American Diabetes Association ) |
| First Posted: | June 6, 2022 Key Record Dates |
| Results First Posted: | August 10, 2022 |
| Last Update Posted: | September 7, 2022 |
| Last Verified: | May 2022 |
| Individual Participant Data (IPD) Sharing Statement: | |
| Plan to Share IPD: | Yes |
| Plan Description: | Deidentified individual data that supports the results will be shared beginning 9 to 36 months following publication provided the investigator who proposes to use the data has approval from an Institutional Review Board (IRB), Independent Ethics Committee (IEC), or Research Ethics Board (REB), as applicable, and executes a data use/sharing agreement with UNC. |
| Supporting Materials: |
Study Protocol Statistical Analysis Plan (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. |
| Studies a U.S. FDA-regulated Drug Product: | Yes |
| Studies a U.S. FDA-regulated Device Product: | No |
| Product Manufactured in and Exported from the U.S.: | Yes |
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bromocriptine dopamine agonist TaqIA polymorphism eating behavior |
food intake overweight obesity |
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Overweight Body Weight Bromocriptine Physiological Effects of Drugs Antiparkinson Agents Anti-Dyskinesia Agents |
Hormone Antagonists Hormones, Hormone Substitutes, and Hormone Antagonists Dopamine Agonists Dopamine Agents Neurotransmitter Agents Molecular Mechanisms of Pharmacological Action |