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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
Recruitment Status : Completed
First Posted : June 6, 2022
Results First Posted : August 10, 2022
Last Update Posted : September 7, 2022
Sponsor:
Collaborator:
American Diabetes Association
Information provided by (Responsible Party):
University of North Carolina, Chapel Hill

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Crossover Assignment;   Masking: Triple (Participant, Investigator, Outcomes Assessor);   Primary Purpose: Diagnostic
Conditions Overweight and Obesity
Eating Behavior
Interventions Drug: Placebo
Drug: Bromocriptine-QR
Enrollment 55
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Bromocriptine, Then Placebo Placebo, Then Bromocriptine
Hide Arm/Group Description

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.

Placebo: 2 capsules, orally administered once

Bromocriptine-QR: 1.6mg (2 0.8mg capsules), orally administered once

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.

Placebo: 2 capsules, orally administered once

Bromocriptine-QR: 1.6mg (2 0.8mg capsules), orally administered once

Period Title: First Intervention (Single 1-Day Visit)
Started 28 27
Completed 28 27
Not Completed 0 0
Period Title: Washout (2 Weeks)
Started 28 27
Completed 24 26
Not Completed 4 1
Reason Not Completed
Lost to Follow-up             0             1
Adverse Event             2             0
Withdrawal by Subject             2             0
Period Title: Second Intervention (Single 1-Day Visit)
Started 24 26
Completed 24 26
Not Completed 0 0
Arm/Group Title All Participants
Hide Arm/Group Description Cross-over design where participants receive either a single dose of bromocriptine or placebo at the initial visit. After a 2-week washout period, they receive the opposite drug at the cross-over visit.
Overall Number of Baseline Participants 55
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 55 participants
22.4  (3.1)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 55 participants
Female
29
  52.7%
Male
26
  47.3%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 55 participants
Hispanic or Latino
8
  14.5%
Not Hispanic or Latino
47
  85.5%
Unknown or Not Reported
0
   0.0%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 55 participants
American Indian or Alaska Native
1
   1.8%
Asian
7
  12.7%
Native Hawaiian or Other Pacific Islander
0
   0.0%
Black or African American
9
  16.4%
White
31
  56.4%
More than one race
2
   3.6%
Unknown or Not Reported
5
   9.1%
Region of Enrollment  
Measure Type: Count of Participants
Unit of measure:  Participants
United States Number Analyzed 55 participants
55
 100.0%
1.Primary Outcome
Title Ad Libitum Food and Beverage Intake (g)
Hide Description 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.
Time Frame Within 15 minutes of completion of the ad libitum period
Hide Outcome Measure Data
Hide Analysis Population Description
Data was collected via an iPad and sometimes recorded no value, as such the decrease in the sample was due to missing data.
Arm/Group Title Bromocriptine Placebo
Hide Arm/Group Description:
All participants; post-bromocriptine administration
All participants; post-placebo administration
Overall Number of Participants Analyzed 47 47
Mean (Standard Deviation)
Unit of Measure: g
Snacks intake 71.5  (58.5) 81.9  (55.9)
Milkshake intake 24.9  (61.2) 33.6  (66.1)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Bromocriptine, Placebo
Comments Snack intake
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.45
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Bromocriptine, Placebo
Comments Milkshake intake
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.28
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
2.Primary Outcome
Title Hedonic Ratings of Food as Measured by a Visual Analog Scale
Hide Description

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).

Time Frame Up to 5 minutes prior to ad libitum period start
Hide Outcome Measure Data
Hide Analysis Population Description
Data was collected via an iPad and sometimes recorded no value, as such the decrease in the sample was due to missing data.
Arm/Group Title Bromocriptine Placebo
Hide Arm/Group Description:
All participants; post-bromocriptine administration
All participants; post-placebo administration
Overall Number of Participants Analyzed 47 47
Mean (Standard Deviation)
Unit of Measure: score on a scale
Snack Pleasantness 32.6  (15.8) 32.2  (15.9)
Snack Desire 11.2  (22.4) 14.6  (22.7)
Milkshake Pleasantness 22.7  (34.3) 32.4  (15.5)
Milkshake Desire -5.1  (40.2) -5.6  (41.2)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Bromocriptine, Placebo
Comments Pleasantness
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.89
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Bromocriptine, Placebo
Comments Desire to consume
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
3.Primary Outcome
Title Change in Voxel-wise Blood Oxygen Level-Dependent (BOLD) Brain Activation in Response to Milkshake Anticipation and Receipt vs. Water
Hide Description

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.

Time Frame Baseline and 2 Weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Participants who had issues with neuroimaging data (e.g., excessive motion, errors with image registration) were excluded from the analysis. As such the decrease in sample is due to suboptimal quality fMRI data.
Arm/Group Title Bromocriptine Placebo
Hide Arm/Group Description:
All participants; post-bromocriptine administration
All participants; post-placebo administration
Overall Number of Participants Analyzed 33 33
Mean (Standard Deviation)
Unit of Measure: arbitrary units
Milkshake cue > Water cue 50.24  (180.43) 15.66  (208.4)
Milkshake taste > Water taste -14.32  (57.68) 3.75  (66.03)
4.Secondary Outcome
Title Ad Libitum Food and Milkshake Intake (g) by TaqIA Allele Status (A1 vs. A2/A2)
Hide Description 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.
Time Frame Within 15 minutes of completion of the ad libitum period
Hide Outcome Measure Data
Hide Analysis Population Description
Data was collected via an iPad and sometimes recorded no value, as such the decrease in the sample was due to missing data.
Arm/Group Title Bromocriptine - TaqIA A1 Bromocriptine - TaqIA A2/A2 Placebo - TaqIA A1 Placebo - TaqIA A2/A2
Hide Arm/Group Description:
Participants with the high risk TaqIA A1 allele; post-bromocriptine administration
Participants without the high risk TaqIA A1 allele; post-bromocriptine administration
Participants with the high risk TaqIA A1 allele; post-placebo administration
Participants without the high risk TaqIA A1 allele; post-placebo administration
Overall Number of Participants Analyzed 28 19 28 19
Mean (Standard Deviation)
Unit of Measure: g
Snacks intake 72.1  (64.3) 70.7  (50.2) 75.2  (46.1) 91.4  (67.7)
Milkshake intake 26.1  (57.9) 23.3  (67.2) 35.5  (66.7) 30.9  (67.1)
5.Secondary Outcome
Title Hedonic Ratings of Milkshake Pleasantness and Desire as Measured by a Visual Analog Scale by TaqIA Allele Status (A1 vs. A2/A2)
Hide Description

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).

Time Frame Up to 5 minutes prior to ad libitum period start
Hide Outcome Measure Data
Hide Analysis Population Description
Data was collected via an iPad and sometimes recorded no value, as such the decrease in the sample was due to missing data.
Arm/Group Title Bromocriptine - TaqIA A1 Bromocriptine - TaqIA A2/A2 Placebo - TaqIA A1 Placebo - TaqIA A2/A2
Hide Arm/Group Description:
Participants with the high risk TaqIA A1 allele; post-bromocriptine administration
Participants without the high risk TaqIA A1 allele; post-bromocriptine administration
Participants with the high risk TaqIA A1 allele; post-placebo administration
Participants without the high risk TaqIA A1 allele; post-placebo administration
Overall Number of Participants Analyzed 28 19 28 19
Mean (Standard Deviation)
Unit of Measure: score on a scale
Pleasantness 27.7  (2.5) 15.1  (38.8) 29.9  (29.7) 12.2  (27.8)
Desire 3.7  (38.8) -18.1  (40.3) 16.6  (20.9) -21.5  (36.2)
6.Secondary Outcome
Title 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)
Hide Description

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.

Time Frame Baseline and 2 Weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Participants who had issues with neuroimaging data (e.g., excessive motion, errors with image registration) were excluded from the analysis. As such the decrease in sample is due to suboptimal quality fMRI data.
Arm/Group Title Bromocriptine - TaqIA A1 Bromocriptine - TaqIA A2/A2 Placebo - TaqIA A1 Placebo - TaqIA A2/A2
Hide Arm/Group Description:
Participants with the high risk TaqIA A1 allele; post-bromocriptine administration
Participants without the high risk TaqIA A1 allele; post-bromocriptine administration
Participants with the high risk TaqIA A1 allele; post-placebo administration
Participants without the high risk TaqIA A1 allele; post-placebo administration
Overall Number of Participants Analyzed 18 15 18 15
Mean (Standard Deviation)
Unit of Measure: arbitrary units
Milkshake cue > Water cue 99.14  (139.86) -8.44  (209.51) 71.54  (176.11) -51.4  (229.74)
Milkshake taste > Water taste -27.21  (41.91) 1.16  (70.73) -14.64  (45.95) 25.82  (80.29)
Time Frame Following administration of initial study intervention at Visit 1 through completion of visit day and again starting with second intervention administration and continuing through study completion, a total of approximately 10 hours for both visits.
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Bromocriptine Placebo
Hide Arm/Group Description Single dose of bromocriptine 1.6mg (2 0.8mg capsules) 2 capsules of placebo (sugar free calcium supplement) matched in shape (circle) and color (white) to bromocriptine
All-Cause Mortality
Bromocriptine Placebo
Affected / at Risk (%) Affected / at Risk (%)
Total   0/54 (0.00%)      0/51 (0.00%)    
Hide Serious Adverse Events
Bromocriptine Placebo
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   0/54 (0.00%)      0/51 (0.00%)    
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Bromocriptine Placebo
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   2/54 (3.70%)      0/51 (0.00%)    
Gastrointestinal disorders     
Vomiting *  1/54 (1.85%)  1 0/51 (0.00%)  0
Nausea *  1/54 (1.85%)  1 0/51 (0.00%)  0
*
Indicates events were collected by non-systematic assessment
Certain Agreements
All Principal Investigators ARE employed by the organization sponsoring the study.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Kyle Burger, PhD, RD, MPH
Organization: University of North Carolina at Chapel Hill
Phone: 9198439933
EMail: Kyle_burger@unc.edu
Layout table for additonal information
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 Submitted: May 31, 2022
First Posted: June 6, 2022
Results First Submitted: June 14, 2022
Results First Posted: August 10, 2022
Last Update Posted: September 7, 2022