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

• 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: University of North Carolina, Chapel Hill
• 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

Participant Flow

Recruitment Details
Pre-assignment Details

Arm/Group Title	Bromocriptine, Then Placebo	Placebo, Then Bromocriptine
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

Baseline Characteristics

Arm/Group Title		All Participants
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
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%

Outcome Measures

1. Primary Outcome

Title	Ad Libitum Food and Beverage Intake (g)
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

Outcome Measure Data

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
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)

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]

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
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

Outcome Measure Data

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
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)

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]

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
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

Outcome Measure Data

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
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)
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

Outcome Measure Data

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
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)
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

Outcome Measure Data

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
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)
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

Outcome Measure Data

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
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)

Adverse Events

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
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%)
Serious Adverse Events
	Bromocriptine		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/54 (0.00%)		0/51 (0.00%)
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

Limitations and Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

Results Point of Contact

• Name/Title: Kyle Burger, PhD, RD, MPH
• Organization: University of North Carolina at Chapel Hill
• Phone: 9198439933
• EMail: Kyle_burger@unc.edu

• 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