Trial Outcomes & Findings for Examination of Bromocriptine on Homeostatic and Hedonic Mechanisms of Food Intake in Individuals at High Risk for T2DM (NCT NCT05405244)

Last Updated: 2022-09-07

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

55 participants

Primary outcome timeframe

Within 15 minutes of completion of the ad libitum period

Results posted on

2022-09-07

Participant Flow

Participant milestones

Participant milestones
Measure	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. Placebo: 2 capsules, orally administered once Bromocriptine-QR: 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. Placebo: 2 capsules, orally administered once Bromocriptine-QR: 1.6mg (2 0.8mg capsules), orally administered once
First Intervention (Single 1-Day Visit) STARTED	28	27
First Intervention (Single 1-Day Visit) COMPLETED	28	27
First Intervention (Single 1-Day Visit) NOT COMPLETED	0	0
Washout (2 Weeks) STARTED	28	27
Washout (2 Weeks) COMPLETED	24	26
Washout (2 Weeks) NOT COMPLETED	4	1
Second Intervention (Single 1-Day Visit) STARTED	24	26
Second Intervention (Single 1-Day Visit) COMPLETED	24	26
Second Intervention (Single 1-Day Visit) NOT COMPLETED	0	0

Reasons for withdrawal

Reasons for withdrawal
Measure	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. Placebo: 2 capsules, orally administered once Bromocriptine-QR: 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. Placebo: 2 capsules, orally administered once Bromocriptine-QR: 1.6mg (2 0.8mg capsules), orally administered once
Washout (2 Weeks) Lost to Follow-up	0	1
Washout (2 Weeks) Adverse Event	2	0
Washout (2 Weeks) Withdrawal by Subject	2	0

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	All Participants n=55 Participants 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.
Age, Continuous	22.4 years STANDARD_DEVIATION 3.1 • n=5 Participants
Sex: Female, Male Female	29 Participants n=5 Participants
Sex: Female, Male Male	26 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	8 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	47 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	1 Participants n=5 Participants
Race (NIH/OMB) Asian	7 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	9 Participants n=5 Participants
Race (NIH/OMB) White	31 Participants n=5 Participants
Race (NIH/OMB) More than one race	2 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	5 Participants n=5 Participants
Region of Enrollment United States	55 Participants n=5 Participants

PRIMARY outcome

Timeframe: Within 15 minutes of completion of the ad libitum period

Population: Data was collected via an iPad and sometimes recorded no value, as such the decrease in the sample was due to missing data.

Outcome measures

Outcome measures
Measure	Bromocriptine n=47 Participants All participants; post-bromocriptine administration	Placebo n=47 Participants All participants; post-placebo administration	Placebo - TaqIA A1 Participants with the high risk TaqIA A1 allele; post-placebo administration	Placebo - TaqIA A2/A2 Participants without the high risk TaqIA A1 allele; post-placebo administration
Ad Libitum Food and Beverage Intake (g) Snacks intake	71.5 g Standard Deviation 58.5	81.9 g Standard Deviation 55.9	—	—
Ad Libitum Food and Beverage Intake (g) Milkshake intake	24.9 g Standard Deviation 61.2	33.6 g Standard Deviation 66.1	—	—

PRIMARY outcome

Timeframe: Up to 5 minutes prior to ad libitum period start

Population: Data was collected via an iPad and sometimes recorded no value, as such the decrease in the sample was due to missing data.

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).

Outcome measures

Outcome measures
Measure	Bromocriptine n=47 Participants All participants; post-bromocriptine administration	Placebo n=47 Participants All participants; post-placebo administration	Placebo - TaqIA A1 Participants with the high risk TaqIA A1 allele; post-placebo administration	Placebo - TaqIA A2/A2 Participants without the high risk TaqIA A1 allele; post-placebo administration
Hedonic Ratings of Food as Measured by a Visual Analog Scale Snack Pleasantness	32.6 score on a scale Standard Deviation 15.8	32.2 score on a scale Standard Deviation 15.9	—	—
Hedonic Ratings of Food as Measured by a Visual Analog Scale Snack Desire	11.2 score on a scale Standard Deviation 22.4	14.6 score on a scale Standard Deviation 22.7	—	—
Hedonic Ratings of Food as Measured by a Visual Analog Scale Milkshake Pleasantness	22.7 score on a scale Standard Deviation 34.3	32.4 score on a scale Standard Deviation 15.5	—	—
Hedonic Ratings of Food as Measured by a Visual Analog Scale Milkshake Desire	-5.1 score on a scale Standard Deviation 40.2	-5.6 score on a scale Standard Deviation 41.2	—	—

PRIMARY outcome

Timeframe: Baseline and 2 Weeks

Population: 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.

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.

Outcome measures

Outcome measures
Measure	Bromocriptine n=33 Participants All participants; post-bromocriptine administration	Placebo n=33 Participants All participants; post-placebo administration	Placebo - TaqIA A1 Participants with the high risk TaqIA A1 allele; post-placebo administration	Placebo - TaqIA A2/A2 Participants without the high risk TaqIA A1 allele; post-placebo administration
Change in Voxel-wise Blood Oxygen Level-Dependent (BOLD) Brain Activation in Response to Milkshake Anticipation and Receipt vs. Water Milkshake cue > Water cue	50.24 arbitrary units Standard Deviation 180.43	15.66 arbitrary units Standard Deviation 208.4	—	—
Change in Voxel-wise Blood Oxygen Level-Dependent (BOLD) Brain Activation in Response to Milkshake Anticipation and Receipt vs. Water Milkshake taste > Water taste	-14.32 arbitrary units Standard Deviation 57.68	3.75 arbitrary units Standard Deviation 66.03	—	—

SECONDARY outcome

Timeframe: Within 15 minutes of completion of the ad libitum period

Population: Data was collected via an iPad and sometimes recorded no value, as such the decrease in the sample was due to missing data.

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.

Outcome measures

Outcome measures
Measure	Bromocriptine n=28 Participants All participants; post-bromocriptine administration	Placebo n=19 Participants All participants; post-placebo administration	Placebo - TaqIA A1 n=28 Participants Participants with the high risk TaqIA A1 allele; post-placebo administration	Placebo - TaqIA A2/A2 n=19 Participants Participants without the high risk TaqIA A1 allele; post-placebo administration
Ad Libitum Food and Milkshake Intake (g) by TaqIA Allele Status (A1 vs. A2/A2) Snacks intake	72.1 g Standard Deviation 64.3	70.7 g Standard Deviation 50.2	75.2 g Standard Deviation 46.1	91.4 g Standard Deviation 67.7
Ad Libitum Food and Milkshake Intake (g) by TaqIA Allele Status (A1 vs. A2/A2) Milkshake intake	26.1 g Standard Deviation 57.9	23.3 g Standard Deviation 67.2	35.5 g Standard Deviation 66.7	30.9 g Standard Deviation 67.1

SECONDARY outcome

Timeframe: Up to 5 minutes prior to ad libitum period start

Population: Data was collected via an iPad and sometimes recorded no value, as such the decrease in the sample was due to missing data.

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).

Outcome measures

Outcome measures
Measure	Bromocriptine n=28 Participants All participants; post-bromocriptine administration	Placebo n=19 Participants All participants; post-placebo administration	Placebo - TaqIA A1 n=28 Participants Participants with the high risk TaqIA A1 allele; post-placebo administration	Placebo - TaqIA A2/A2 n=19 Participants Participants without the high risk TaqIA A1 allele; post-placebo administration
Hedonic Ratings of Milkshake Pleasantness and Desire as Measured by a Visual Analog Scale by TaqIA Allele Status (A1 vs. A2/A2) Pleasantness	27.7 score on a scale Standard Deviation 2.5	15.1 score on a scale Standard Deviation 38.8	29.9 score on a scale Standard Deviation 29.7	12.2 score on a scale Standard Deviation 27.8
Hedonic Ratings of Milkshake Pleasantness and Desire as Measured by a Visual Analog Scale by TaqIA Allele Status (A1 vs. A2/A2) Desire	3.7 score on a scale Standard Deviation 38.8	-18.1 score on a scale Standard Deviation 40.3	16.6 score on a scale Standard Deviation 20.9	-21.5 score on a scale Standard Deviation 36.2

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Bromocriptine n=18 Participants All participants; post-bromocriptine administration	Placebo n=15 Participants All participants; post-placebo administration	Placebo - TaqIA A1 n=18 Participants Participants with the high risk TaqIA A1 allele; post-placebo administration	Placebo - TaqIA A2/A2 n=15 Participants Participants without the high risk TaqIA A1 allele; post-placebo administration
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) Milkshake cue > Water cue	99.14 arbitrary units Standard Deviation 139.86	-8.44 arbitrary units Standard Deviation 209.51	71.54 arbitrary units Standard Deviation 176.11	-51.4 arbitrary units Standard Deviation 229.74
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) Milkshake taste > Water taste	-27.21 arbitrary units Standard Deviation 41.91	1.16 arbitrary units Standard Deviation 70.73	-14.64 arbitrary units Standard Deviation 45.95	25.82 arbitrary units Standard Deviation 80.29

Adverse Events

Bromocriptine

Serious events: 0 serious events

Other events: 2 other events

Deaths: 0 deaths

Placebo

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	Bromocriptine n=54 participants at risk Single dose of bromocriptine 1.6mg (2 0.8mg capsules)	Placebo n=51 participants at risk 2 capsules of placebo (sugar free calcium supplement) matched in shape (circle) and color (white) to bromocriptine
Gastrointestinal disorders Vomiting	1.9% 1/54 • Number of events 1 • 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.	0.00% 0/51 • 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.
Gastrointestinal disorders Nausea	1.9% 1/54 • Number of events 1 • 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.	0.00% 0/51 • 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.

Additional Information

Kyle Burger, PhD, RD, MPH

University of North Carolina at Chapel Hill

Phone: 9198439933

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place