Trial Outcomes & Findings for Dopamine Receptor Contributions to Prediction Error and Reversal Learning in Anorexia Nervosa (NCT NCT04128683)

Last Updated: 2025-04-11

Results Overview

This task measures responsiveness to unexpected stimulus in the dopamine related brain circuitry. Study participants in both the healthy control group and anorexia nervosa group completed 3 fMRI scans. Prior to each scan subjects were administered one of three study medications (amisulpride, bromocriptine, or placebo). During the fMRI scan, subjects completed a taste reward prediction error task where they viewed visual stimuli and then received one of three conditions: sweet taste, neutral taste, or no solution. 20 percent of stimulus receipt was unexpected, that is there is a mismatch between expectation and outcome. Using a region of interest (ROI)-based approach, brain activation percent signal change values were extracted from the brain images for each subject and compared across groups and medication scans. A repeated measures ANOVA was used to calculate the mean brain activation for each group and each medication scan.

Recruitment status

COMPLETED

Study phase

EARLY_PHASE1

Target enrollment

31 participants

Primary outcome timeframe

The outcome measure was assessed during the taste MRI task on each of the 3 intervention scan days over the course of 9 to 12 days

Results posted on

2025-04-11

Participant Flow

31 individuals were recruited and enrolled in the study between 10/20/2020 and 6/22/2023 from the San Diego community and the UC San Diego Health Eating Disorders Center for Treatment and Research. Subjects completed several screening processes to determine eligibility and after eligibility was confirmed, were randomly assigned to the study arms. Of those not randomized, 18 individuals were excluded (10 screen failures, 1 voluntary withdrawal by subject, and 7 withdrawals by PI).

Of the 31 subjects enrolled, 13 subjects were randomized, 7 participants in the healthy control group and 6 participants in the anorexia nervosa group. Each subject was assigned randomly to one of the 6 study arms. These study arms had different orders of the medication intervention administered at each scan. All subjects received each of the 3 study interventions (amysulpride, bromocriptine, placebo), however, the order of medication intervention at each scan varied based on the randomization.

Participant milestones

Participant milestones
Measure	Healthy Controls Subjects at normal weight without psychiatric or eating disorder history	Anorexia Nervosa Subjects diagnosed with restricting-type anorexia nervosa according to DSM-V criteria
1st Intervention (1 Day) STARTED	7	6
1st Intervention (1 Day) 1st Intervention = Amysulpride	3	2
1st Intervention (1 Day) 1st Intervention = Bromocriptine	1	2
1st Intervention (1 Day) 1st Intervention = Placebo	3	2
1st Intervention (1 Day) COMPLETED	7	6
1st Intervention (1 Day) NOT COMPLETED	0	0
Washout Period (2-3 Days) STARTED	7	6
Washout Period (2-3 Days) COMPLETED	7	6
Washout Period (2-3 Days) NOT COMPLETED	0	0
2nd Intervention (1 Day) STARTED	7	6
2nd Intervention (1 Day) 2nd Intervention = Amysulpride.	2	2
2nd Intervention (1 Day) 2nd Intervention = Bromocriptine	3	2
2nd Intervention (1 Day) 2nd Intervention = Placebo	2	2
2nd Intervention (1 Day) COMPLETED	7	6
2nd Intervention (1 Day) NOT COMPLETED	0	0
3rd Intervention (1 Day) STARTED	7	6
3rd Intervention (1 Day) 3rd Intervention = Amysulpride	2	2
3rd Intervention (1 Day) 3rd Intervention = Bromocriptine	3	2
3rd Intervention (1 Day) 3rd Intervention = Placebo	2	2
3rd Intervention (1 Day) COMPLETED	7	6
3rd Intervention (1 Day) NOT COMPLETED	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Dopamine Receptor Contributions to Prediction Error and Reversal Learning in Anorexia Nervosa

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Healthy Controls n=7 Participants Subjects at normal weight without psychiatric or eating disorder history	Anorexia Nervosa n=6 Participants Subjects diagnosed with restricting-type anorexia nervosa according to DSM-V criteria	Total n=13 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	7 Participants n=5 Participants	6 Participants n=7 Participants	13 Participants n=5 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Continuous	24.09 Years STANDARD_DEVIATION 4.02 • n=5 Participants	21.43 Years STANDARD_DEVIATION 2.25 • n=7 Participants	22.86 Years STANDARD_DEVIATION 3.47 • n=5 Participants
Sex: Female, Male Female	7 Participants n=5 Participants	6 Participants n=7 Participants	13 Participants n=5 Participants
Sex: Female, Male Male	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	3 Participants n=5 Participants	2 Participants n=7 Participants	5 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	4 Participants n=5 Participants	4 Participants n=7 Participants	8 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	2 Participants n=5 Participants	0 Participants n=7 Participants	2 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) White	4 Participants n=5 Participants	4 Participants n=7 Participants	8 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Region of Enrollment United States	7 Participants n=5 Participants	6 Participants n=7 Participants	13 Participants n=5 Participants
Body Mass Index	22.41 kg/m^2 STANDARD_DEVIATION 1.69 • n=5 Participants	18.63 kg/m^2 STANDARD_DEVIATION 0.94 • n=7 Participants	20.67 kg/m^2 STANDARD_DEVIATION 2.38 • n=5 Participants
Eating Disorder Inventory 3 - Drive for Thinness Subscale	0.57 units on a scale STANDARD_DEVIATION 0.79 • n=5 Participants	19.5 units on a scale STANDARD_DEVIATION 4.41 • n=7 Participants	9.30 units on a scale STANDARD_DEVIATION 10.24 • n=5 Participants
Eating Disorder Inventory 3 - Body Dissatisfaction Subscale	5.00 units on a scale STANDARD_DEVIATION 3.78 • n=5 Participants	30.33 units on a scale STANDARD_DEVIATION 4.76 • n=7 Participants	16.69 units on a scale STANDARD_DEVIATION 13.76 • n=5 Participants
Eating Disorders Examination Questionnaire Global Score	0.33 units on a scale STANDARD_DEVIATION 0.41 • n=5 Participants	3.62 units on a scale STANDARD_DEVIATION 0.88 • n=7 Participants	1.85 units on a scale STANDARD_DEVIATION 1.80 • n=5 Participants

PRIMARY outcome

Timeframe: The outcome measure was assessed during the taste MRI task on each of the 3 intervention scan days over the course of 9 to 12 days

Population: brain imaging data was pre-processed and brain response was analyzed across groups (healthy control group versus anorexia nervosa group) and within group for each medication. One participant in the anorexia nervosa group had to be excluded from the analysis results due to excessive movement throughout the MRI scan.

Outcome measures

Outcome measures
Measure	Healthy Controls Placebo Scan n=7 Participants Subjects at normal weight without psychiatric or eating disorder history. Placebo medication was administered 3 hours prior to the start of the functional magnetic resonance imaging (fMRI) Taste Reward Task.	Anorexia Nervosa Placebo Scan n=5 Participants Subjects diagnosed with restricting-type anorexia nervosa according to DSM-V criteria. Placebo medication was administered 3 hours prior to the start of the functional magnetic resonance imaging (fMRI) Taste Reward Task.	Healthy Controls Amisulpride Medication Scan n=7 Participants Subjects at normal weight without psychiatric or eating disorder history. Amisulpride medication was administered 3 hours prior to the start of the functional magnetic resonance imaging (fMRI) Taste Reward Task.	Anorexia Nervosa Amisulpride Medication Scan n=5 Participants Subjects diagnosed with restricting-type anorexia nervosa according to DSM-V criteria. Amisulpride medication was administered 3 hours prior to the start of the functional magnetic resonance imaging (fMRI) Taste Reward Task.	Healthy Controls Bromocriptine Medication Scan n=7 Participants Subjects at normal weight without psychiatric or eating disorder history. Bromocriptine medication was administered 3 hours prior to the start of the functional magnetic resonance imaging (fMRI) Taste Reward Task.	Anorexia Nervosa Bromocriptine Medication Scan n=5 Participants Subjects diagnosed with restricting-type anorexia nervosa according to DSM-V criteria. Bromocriptine medication was administered 3 hours prior to the start of the functional magnetic resonance imaging (fMRI) Taste Reward Task.
Measurement of Brain Activation (Measured in Percent Signal Change) During a Prediction Error Taste Reward Task Using Functional Magnetic Resonance Imaging (fMRI). Left Ventral Insula Brain Activation	5.847 Percent Signal Change Standard Error 1.349	5.083 Percent Signal Change Standard Error 1.596	0.991 Percent Signal Change Standard Error 0.938	-1.047 Percent Signal Change Standard Error 1.109	1.116 Percent Signal Change Standard Error 1.225	-0.148 Percent Signal Change Standard Error 1.450
Measurement of Brain Activation (Measured in Percent Signal Change) During a Prediction Error Taste Reward Task Using Functional Magnetic Resonance Imaging (fMRI). Right Ventral Insula Brain Activation	4.095 Percent Signal Change Standard Error 0.669	4.860 Percent Signal Change Standard Error 0.791	0.883 Percent Signal Change Standard Error 0.716	-0.137 Percent Signal Change Standard Error 0.847	4.117 Percent Signal Change Standard Error 0.987	2.650 Percent Signal Change Standard Error 1.167
Measurement of Brain Activation (Measured in Percent Signal Change) During a Prediction Error Taste Reward Task Using Functional Magnetic Resonance Imaging (fMRI). Left Ventral Striatum Brain Activation	2.081 Percent Signal Change Standard Error 0.582	1.767 Percent Signal Change Standard Error 0.689	1.475 Percent Signal Change Standard Error 1.153	-0.599 Percent Signal Change Standard Error 1.365	1.122 Percent Signal Change Standard Error 0.951	1.328 Percent Signal Change Standard Error 1.126
Measurement of Brain Activation (Measured in Percent Signal Change) During a Prediction Error Taste Reward Task Using Functional Magnetic Resonance Imaging (fMRI). Right Ventral Striatum Brain Activation	1.583 Percent Signal Change Standard Error 0.660	2.367 Percent Signal Change Standard Error 0.781	1.728 Percent Signal Change Standard Error 1.020	-0.799 Percent Signal Change Standard Error 1.207	1.642 Percent Signal Change Standard Error 0.304	1.732 Percent Signal Change Standard Error 0.359
Measurement of Brain Activation (Measured in Percent Signal Change) During a Prediction Error Taste Reward Task Using Functional Magnetic Resonance Imaging (fMRI). Left Inferior Orbital Frontal Cortex Brain Activation	-0.199 Percent Signal Change Standard Error 0.789	0.544 Percent Signal Change Standard Error 0.934	0.988 Percent Signal Change Standard Error 0.686	-1.222 Percent Signal Change Standard Error 0.811	0.646 Percent Signal Change Standard Error 1.038	1.171 Percent Signal Change Standard Error 1.229
Measurement of Brain Activation (Measured in Percent Signal Change) During a Prediction Error Taste Reward Task Using Functional Magnetic Resonance Imaging (fMRI). Right Inferior Orbital Frontal Cortex Brain Activation	4.333 Percent Signal Change Standard Error 0.427	4.138 Percent Signal Change Standard Error 0.505	0.396 Percent Signal Change Standard Error 0.803	-0.699 Percent Signal Change Standard Error 0.950	5.512 Percent Signal Change Standard Error 1.244	4.774 Percent Signal Change Standard Error 1.472

PRIMARY outcome

Timeframe: The outcome measure was assessed during the taste MRI task on each of the 3 intervention scan days over the course of 9 to 12 days

Population: brain imaging data was pre-processed and brain response was analyzed across groups (healthy control group versus anorexia nervosa group) and within group for each medication

Study participants in both the healthy control group and anorexia nervosa group completed 3 fMRI scans. Prior to each scan subjects were administered one of three study medications (amisulpride, bromocriptine, or placebo). During the fMRI scan, subjects completed a taste reward prediction error task where they viewed visual stimuli and then received one of three conditions: sweet taste, neutral taste, or no solution. Using a region of interest (ROI)-based approach, brain activation percent signal change values were extracted from the brain images for each subject and compared across groups and medication scans. Here only stimulus expectation data were analyzed. A repeated measures ANOVA was used to calculate the mean brain activation for each group and each medication scan.