Overweight and ObesityPhase 3NCT05405244
Examination of Bromocriptine on Homeostatic and Hedonic Mechanisms of Food Intake in Individuals at High Risk for T2DM
A Phase 3 study testing Bromocriptine-QR in people with Overweight and Obesity and Eating Behavior, run by University of North Carolina, Chapel Hill at 1 site in United States.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 to 35 yearsHealthy volunteers can take part
- Conditions the study is for
- Overweight and Obesity, Eating Behavior
- What is being tested?
- Bromocriptine-QR
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 55 participants
- Where
- 1 siteUnited States
- Study dates
- 19 Sep 2017to 19 Sep 2019
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 35 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- Baseline BMI between 25 and 35
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
United States1 site
University of North Carolina, Chapel Hill
Chapel Hill, North Carolina, 27599
About this study
Official title: A Multimodel Examination of Bromocriptine on Homeostatic and Hedonic Mechanisms of Food Intake in Individuals at High Risk for Type 2 Diabetes
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.
Read the 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
- Being tested
- Placebo, Bromocriptine-QR
- Keywords
- bromocriptine, dopamine agonist, TaqIA polymorphism, eating behavior, food intake, overweight, obesity
- Medical subject headings
- Overweight, Obesity, Feeding Behavior
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PlaceboDrug
Also called placebo (calcium supplement)
2 capsules, orally administered once
Bromocriptine-QRDrug
Also called quick-release (QR) bromocriptine (cycloset)
1.6mg (2 0.8mg capsules), orally administered once
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: Drug: Placebo; Drug: Bromocriptine-QR |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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).
Measured: 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.
Measured: Baseline and 2 Weeks
Secondary outcomes (3)
Ad Libitum Food and Milkshake Intake (g) by TaqIA Allele Status (A1 vs. A2/A2)
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.
Measured: 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)
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).
Measured: 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)
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.
Measured: Baseline and 2 Weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Jun 2022
- Study start19 Sep 2017
- Primary completion19 Sep 2019
- Study completion19 Sep 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Overweight and ObesityStudies of the same condition, open and under way.
- More trials run by University of North Carolina, Chapel HillThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Diagnosis
- Allocation
- Randomised
- Intervention model
- Crossover
- 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 blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 55 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of North Carolina, Chapel Hill
- Sponsor type
- University, hospital or other
- Collaborators
- American Diabetes Association
- Responsible party
- Sponsor
- Investigators
- Kyle S Burger, MPH, RD, PhD, Principal investigator, University of North Carolina, Chapel Hill
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05405244
- Sponsor's protocol ID
- 16-3177
- Other IDs
- 1-17-JDF-031
- Status last verified
- May 2022
- First submitted
- 31 May 2022
- Last updated
- 7 Sep 2022
- Results posted
- Yes, on ClinicalTrials.gov
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: 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.
Study at a glance
From the registry record, last updated by the sponsor on 7 Sep 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Multimodel Examination of Bromocriptine on Homeostatic and Hedonic Mechanisms of Food Intake in Individuals at High Risk for Type 2 Diabetes
- ClinicalTrials.gov ID
- NCT05405244
- Acronym / sponsor ID
- 16-3177
- Conditions
- Overweight and Obesity, Eating Behavior
- Keywords
- bromocriptine, dopamine agonist, TaqIA polymorphism, eating behavior, food intake, overweight, obesity
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 55 participants (actual)
- Lead sponsor
- University of North Carolina, Chapel HillUniversity, hospital or other
- Collaborators
- American Diabetes Association
- Study start
- 19 Sep 2017 (actual)
- Primary completion
- 19 Sep 2019 (actual)
- Study completion
- 19 Sep 2019 (actual)
- First posted
- 6 Jun 2022 (actual)
- Results
- Posted 10 Aug 2022
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Diagnosis
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 2
- 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.
| Arm | Type | Receives |
|---|---|---|
| Bromocriptine, then Placebo | Other | Drug: Placebo, Drug: Bromocriptine-QRDuring 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. |
| Placebo, then Bromocriptine | Other | Drug: Placebo, Drug: Bromocriptine-QRDuring 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. |
Who may qualify
- Ages
- 18 to 35 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (1 listed)
- Baseline BMI between 25 and 35
Key exclusion criteria (8 listed)
- 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)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| PlaceboAlso: placebo (calcium supplement)2 capsules, orally administered once | Drug | Bromocriptine, then Placebo, Placebo, then Bromocriptine |
| Bromocriptine-QRAlso: quick-release (QR) bromocriptine (cycloset)1.6mg (2 0.8mg capsules), orally administered once | Drug | Bromocriptine, then Placebo, Placebo, then Bromocriptine |
Primary outcome
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.
3 secondary outcomes
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
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
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
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Sep 2022.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: Yes. 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Kyle S Burger, MPH, RD, PhD principal investigator
University of North Carolina, Chapel Hill
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Bromocriptine-QR in people with Overweight and Obesity and Eating Behavior, run by University of North Carolina, Chapel Hill at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 7 Sep 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 10 Aug 2022). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Ad Libitum Food and Beverage Intake (g) (time frame: Within 15 minutes of completion of the ad libitum period). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 Sep 2022.