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

A Multimodel Examination of Bromocriptine on Homeostatic and Hedonic Mechanisms of Food Intake in Individuals at High Risk for Type 2 Diabetes

Status
Completed
Phases
Phase 3
Study type
Interventional
Source
ClinicalTrials.gov
Registry ID
NCT05405244
Enrollment
55
Registered
2022-06-06
Start date
2017-09-19
Completion date
2019-09-19
Last updated
2022-09-07

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Eating Behavior, Overweight and Obesity

Keywords

bromocriptine, dopamine agonist, TaqIA polymorphism, eating behavior, food intake, overweight, obesity

Brief 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 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.

Interventions

DRUGPlacebo

2 capsules, orally administered once

DRUGBromocriptine-QR

1.6mg (2 0.8mg capsules), orally administered once

Sponsors

American Diabetes Association
CollaboratorOTHER
University of North Carolina, Chapel Hill
Lead SponsorOTHER

Study design

Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
DIAGNOSTIC
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)

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.

Eligibility

Sex/Gender
ALL
Age
18 Years to 35 Years
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

Design outcomes

Primary

MeasureTime frameDescription
Ad Libitum Food and Beverage Intake (g)Within 15 minutes of completion of the ad libitum periodAd 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 ScaleUp to 5 minutes prior to ad libitum period startTesting 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. WaterBaseline and 2 WeeksThe 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.

Secondary

MeasureTime frameDescription
Ad Libitum Food and Milkshake Intake (g) by TaqIA Allele Status (A1 vs. A2/A2)Within 15 minutes of completion of the ad libitum periodTesting 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)Up to 5 minutes prior to ad libitum period startTesting 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)Baseline and 2 WeeksThe 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.

Countries

United States

Participant flow

Participants by arm

ArmCount
All 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.
55
Total55

Withdrawals & dropouts

PeriodReasonFG000FG001
Washout (2 Weeks)Adverse Event20
Washout (2 Weeks)Lost to Follow-up01
Washout (2 Weeks)Withdrawal by Subject20

Baseline characteristics

CharacteristicAll Participants
Age, Continuous22.4 years
STANDARD_DEVIATION 3.1
Ethnicity (NIH/OMB)
Hispanic or Latino
8 Participants
Ethnicity (NIH/OMB)
Not Hispanic or Latino
47 Participants
Ethnicity (NIH/OMB)
Unknown or Not Reported
0 Participants
Race (NIH/OMB)
American Indian or Alaska Native
1 Participants
Race (NIH/OMB)
Asian
7 Participants
Race (NIH/OMB)
Black or African American
9 Participants
Race (NIH/OMB)
More than one race
2 Participants
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
0 Participants
Race (NIH/OMB)
Unknown or Not Reported
5 Participants
Race (NIH/OMB)
White
31 Participants
Region of Enrollment
United States
55 Participants
Sex: Female, Male
Female
29 Participants
Sex: Female, Male
Male
26 Participants

Adverse events

Event typeEG000
affected / at risk
EG001
affected / at risk
deaths
Total, all-cause mortality
0 / 540 / 51
other
Total, other adverse events
2 / 540 / 51
serious
Total, serious adverse events
0 / 540 / 51

Outcome results

Primary

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.

Time frame: 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.

ArmMeasureGroupValue (MEAN)Dispersion
BromocriptineAd Libitum Food and Beverage Intake (g)Snacks intake71.5 gStandard Deviation 58.5
BromocriptineAd Libitum Food and Beverage Intake (g)Milkshake intake24.9 gStandard Deviation 61.2
PlaceboAd Libitum Food and Beverage Intake (g)Snacks intake81.9 gStandard Deviation 55.9
PlaceboAd Libitum Food and Beverage Intake (g)Milkshake intake33.6 gStandard Deviation 66.1
Comparison: Snack intakep-value: 0.45t-test, 2 sided
Comparison: Milkshake intakep-value: 0.28t-test, 2 sided
Primary

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.

Time frame: 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.

ArmMeasureGroupValue (MEAN)Dispersion
BromocriptineChange in Voxel-wise Blood Oxygen Level-Dependent (BOLD) Brain Activation in Response to Milkshake Anticipation and Receipt vs. WaterMilkshake taste > Water taste-14.32 arbitrary unitsStandard Deviation 57.68
BromocriptineChange in Voxel-wise Blood Oxygen Level-Dependent (BOLD) Brain Activation in Response to Milkshake Anticipation and Receipt vs. WaterMilkshake cue > Water cue50.24 arbitrary unitsStandard Deviation 180.43
PlaceboChange in Voxel-wise Blood Oxygen Level-Dependent (BOLD) Brain Activation in Response to Milkshake Anticipation and Receipt vs. WaterMilkshake cue > Water cue15.66 arbitrary unitsStandard Deviation 208.4
PlaceboChange in Voxel-wise Blood Oxygen Level-Dependent (BOLD) Brain Activation in Response to Milkshake Anticipation and Receipt vs. WaterMilkshake taste > Water taste3.75 arbitrary unitsStandard Deviation 66.03
Primary

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).

Time frame: 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.

ArmMeasureGroupValue (MEAN)Dispersion
BromocriptineHedonic Ratings of Food as Measured by a Visual Analog ScaleSnack Desire11.2 score on a scaleStandard Deviation 22.4
BromocriptineHedonic Ratings of Food as Measured by a Visual Analog ScaleSnack Pleasantness32.6 score on a scaleStandard Deviation 15.8
BromocriptineHedonic Ratings of Food as Measured by a Visual Analog ScaleMilkshake Pleasantness22.7 score on a scaleStandard Deviation 34.3
BromocriptineHedonic Ratings of Food as Measured by a Visual Analog ScaleMilkshake Desire-5.1 score on a scaleStandard Deviation 40.2
PlaceboHedonic Ratings of Food as Measured by a Visual Analog ScaleMilkshake Desire-5.6 score on a scaleStandard Deviation 41.2
PlaceboHedonic Ratings of Food as Measured by a Visual Analog ScaleMilkshake Pleasantness32.4 score on a scaleStandard Deviation 15.5
PlaceboHedonic Ratings of Food as Measured by a Visual Analog ScaleSnack Pleasantness32.2 score on a scaleStandard Deviation 15.9
PlaceboHedonic Ratings of Food as Measured by a Visual Analog ScaleSnack Desire14.6 score on a scaleStandard Deviation 22.7
Comparison: Pleasantnessp-value: 0.89t-test, 2 sided
Comparison: Desire to consumep-value: <0.001t-test, 2 sided
Secondary

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.

Time frame: 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.

ArmMeasureGroupValue (MEAN)Dispersion
BromocriptineAd Libitum Food and Milkshake Intake (g) by TaqIA Allele Status (A1 vs. A2/A2)Snacks intake72.1 gStandard Deviation 64.3
BromocriptineAd Libitum Food and Milkshake Intake (g) by TaqIA Allele Status (A1 vs. A2/A2)Milkshake intake26.1 gStandard Deviation 57.9
PlaceboAd Libitum Food and Milkshake Intake (g) by TaqIA Allele Status (A1 vs. A2/A2)Milkshake intake23.3 gStandard Deviation 67.2
PlaceboAd Libitum Food and Milkshake Intake (g) by TaqIA Allele Status (A1 vs. A2/A2)Snacks intake70.7 gStandard Deviation 50.2
Placebo - TaqIA A1Ad Libitum Food and Milkshake Intake (g) by TaqIA Allele Status (A1 vs. A2/A2)Snacks intake75.2 gStandard Deviation 46.1
Placebo - TaqIA A1Ad Libitum Food and Milkshake Intake (g) by TaqIA Allele Status (A1 vs. A2/A2)Milkshake intake35.5 gStandard Deviation 66.7
Placebo - TaqIA A2/A2Ad Libitum Food and Milkshake Intake (g) by TaqIA Allele Status (A1 vs. A2/A2)Snacks intake91.4 gStandard Deviation 67.7
Placebo - TaqIA A2/A2Ad Libitum Food and Milkshake Intake (g) by TaqIA Allele Status (A1 vs. A2/A2)Milkshake intake30.9 gStandard Deviation 67.1
Secondary

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.

Time frame: 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.

ArmMeasureGroupValue (MEAN)Dispersion
BromocriptineChange 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 cue99.14 arbitrary unitsStandard Deviation 139.86
BromocriptineChange 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 unitsStandard Deviation 41.91
PlaceboChange 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 taste1.16 arbitrary unitsStandard Deviation 70.73
PlaceboChange 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-8.44 arbitrary unitsStandard Deviation 209.51
Placebo - TaqIA A1Change 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 cue71.54 arbitrary unitsStandard Deviation 176.11
Placebo - TaqIA A1Change 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-14.64 arbitrary unitsStandard Deviation 45.95
Placebo - TaqIA A2/A2Change 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-51.4 arbitrary unitsStandard Deviation 229.74
Placebo - TaqIA A2/A2Change 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 taste25.82 arbitrary unitsStandard Deviation 80.29
Secondary

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).

Time frame: 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.

ArmMeasureGroupValue (MEAN)Dispersion
BromocriptineHedonic Ratings of Milkshake Pleasantness and Desire as Measured by a Visual Analog Scale by TaqIA Allele Status (A1 vs. A2/A2)Desire3.7 score on a scaleStandard Deviation 38.8
BromocriptineHedonic Ratings of Milkshake Pleasantness and Desire as Measured by a Visual Analog Scale by TaqIA Allele Status (A1 vs. A2/A2)Pleasantness27.7 score on a scaleStandard Deviation 2.5
PlaceboHedonic Ratings of Milkshake Pleasantness and Desire as Measured by a Visual Analog Scale by TaqIA Allele Status (A1 vs. A2/A2)Pleasantness15.1 score on a scaleStandard Deviation 38.8
PlaceboHedonic Ratings of Milkshake Pleasantness and Desire as Measured by a Visual Analog Scale by TaqIA Allele Status (A1 vs. A2/A2)Desire-18.1 score on a scaleStandard Deviation 40.3
Placebo - TaqIA A1Hedonic Ratings of Milkshake Pleasantness and Desire as Measured by a Visual Analog Scale by TaqIA Allele Status (A1 vs. A2/A2)Pleasantness29.9 score on a scaleStandard Deviation 29.7
Placebo - TaqIA A1Hedonic Ratings of Milkshake Pleasantness and Desire as Measured by a Visual Analog Scale by TaqIA Allele Status (A1 vs. A2/A2)Desire16.6 score on a scaleStandard Deviation 20.9
Placebo - TaqIA A2/A2Hedonic Ratings of Milkshake Pleasantness and Desire as Measured by a Visual Analog Scale by TaqIA Allele Status (A1 vs. A2/A2)Desire-21.5 score on a scaleStandard Deviation 36.2
Placebo - TaqIA A2/A2Hedonic Ratings of Milkshake Pleasantness and Desire as Measured by a Visual Analog Scale by TaqIA Allele Status (A1 vs. A2/A2)Pleasantness12.2 score on a scaleStandard Deviation 27.8

Source: ClinicalTrials.gov · Data processed: Feb 4, 2026