Clinical trial NCT04128683
Conditions: Anorexia Nervosa
Sponsor: University of California, San Diego
Start date: 2020-10-20; Completion date: 2025-01-01
Enrollment: 31 participants; Allocation: RANDOMIZED; Intervention model: CROSSOVER

Brief summary:
Anorexia nervosa (AN) is an eating disorder associated with intense fear of weight gain, food refusal, and severe weight loss. AN has the highest mortality rate among the psychiatric disorders; however, little is known about biomarkers, and no medication has been approved for AN. Many individuals only partially recover, and treatment options, especially for the psychological components of the illness, are not very effective, highlighting the need for more effective treatments.

Brain reward pathways have a direct impact on the drive to eat, and a variety of neuroimaging studies have suggested altered reward processing in AN. The neurotransmitter dopamine has a central role in the reward circuitry to drive food approach, and the dynamic interplay between dopamine receptor response and food restriction could have implications for the pathophysiology of AN. Dopamine-related brain function has been studied indirectly using functional magnetic resonance brain imaging (fMRI) and tasks that deliver reward stimuli unexpectedly, that elicit the so-called prediction error (PE) response.

Research in AN showed repeatedly altered PE processing suggesting altered dopamine circuit function in the disorder.

Dopamine and PE response have also been associated with altered reversal learning, which has important treatment implication for AN as reversal learning is impaired in the disorder and modulation of the dopamine system could improve treatment.

Detailed description:

Arms: arm 1: Individuals in the healthy control group were randomized to the following scan order. Participants were administered a study medication or placebo 3 hours prior to the start of the scan. The participant did not know what study medication they received for each scan:

Scan 1: Placebo(single dose, 3 hours pre-scan) Scan 2: Amisulpride (single dose, 400 mg, 3 hours pre-scan) Scan 3: Bromocriptine (single dose, 1.25 mg, 3 hours pre-scan) arm 2: Individuals in the healthy control group were randomized to the following scan order. Participants were administered a study medication or placebo 3 hours prior to the start of the scan. The participant did not know what study medication they received for each scan:

Scan 1: Placebo(single dose, 3 hours pre-scan) Scan 2: Bromocriptine (single dose, 1.25 mg, 3 hours pre-scan) Scan 3: Amisulpride (single dose, 400 mg, 3 hours pre-scan) arm 3: Individuals in the healthy control group were randomized to the following scan order. Participants were administered a study medication or placebo 3 hours prior to the start of the scan. The participant did not know what study medication they received for each scan:

Scan 1: Amisulpride (single dose, 400 mg, 3 hours pre-scan) Scan 2: Placebo(single dose, 3 hours pre-scan) Scan 3: Bromocriptine (single dose, 1.25 mg, 3 hours pre-scan) arm 4: Individuals in the healthy control group were randomized to the following scan order. Participants were administered a study medication or placebo 3 hours prior to the start of the scan. The participant did not know what study medication they received for each scan:

Scan 1: Amisulpride (single dose, 400 mg, 3 hours pre-scan) Scan 2: Bromocriptine (single dose, 1.25 mg, 3 hours pre-scan) Scan 3: Placebo(single dose, 3 hours pre-scan) arm 5: Individuals in the healthy control group were randomized to the following scan order. Participants were administered a study medication or placebo 3 hours prior to the start of the scan. The participant did not know what study medication they received for each scan:

Scan 1: Bromocriptine (single dose, 1.25 mg, 3 hours pre-scan) Scan 2: Placebo(single dose, 3 hours pre-scan) Scan 3: Amisulpride (single dose, 400 mg, 3 hours pre-scan) arm 6: Individuals in the healthy control group were randomized to the following scan order. Participants were administered a study medication or placebo 3 hours prior to the start of the scan. The participant did not know what study medication they received for each scan:

Scan 1: Bromocriptine (single dose, 1.25 mg, 3 hours pre-scan) Scan 2: Amisulpride (single dose, 400 mg, 3 hours pre-scan) Scan 3: Placebo(single dose, 3 hours pre-scan) arm 7: Individuals in the anorexia nervosa group were randomized to the following scan order. Participants were administered a study medication or placebo 3 hours prior to the start of the scan. The participant did not know what study medication they received for each scan:

Scan 1: Placebo(single dose, 3 hours pre-scan) Scan 2: Amisulpride (single dose, 400 mg, 3 hours pre-scan) Scan 3: Bromocriptine (single dose, 1.25 mg, 3 hours pre-scan) arm 8: Individuals in the anorexia nervosa group were randomized to the following scan order. Participants were administered a study medication or placebo 3 hours prior to the start of the scan. The participant did not know what study medication they received for each scan:

Scan 1: Placebo(single dose, 3 hours pre-scan) Scan 2: Bromocriptine (single dose, 1.25 mg, 3 hours pre-scan) Scan 3: Amisulpride (single dose, 400 mg, 3 hours pre-scan) arm 9: Individuals in the anorexia nervosa group were randomized to the following scan order. Participants were administered a study medication or placebo 3 hours prior to the start of the scan. The participant did not know what study medication they received for each scan:

Scan 1: Amisulpride (single dose, 400 mg, 3 hours pre-scan) Scan 2: Placebo(single dose, 3 hours pre-scan) Scan 3: Bromocriptine (single dose, 1.25 mg, 3 hours pre-scan) arm 10: Individuals in the anorexia nervosa group were randomized to the following scan order. Participants were administered a study medication or placebo 3 hours prior to the start of the scan. The participant did not know what study medication they received for each scan:

Scan 1: Amisulpride (single dose, 400 mg, 3 hours pre-scan) Scan 2: Bromocriptine (single dose, 1.25 mg, 3 hours pre-scan) Scan 3: Placebo(single dose, 3 hours pre-scan) arm 11: Individuals in the anorexia nervosa group were randomized to the following scan order. Participants were administered a study medication or placebo 3 hours prior to the start of the scan. The participant did not know what study medication they received for each scan:

Scan 1: Bromocriptine (single dose, 1.25 mg, 3 hours pre-scan) Scan 2: Placebo(single dose, 3 hours pre-scan) Scan 3: Amisulpride (single dose, 400 mg, 3 hours pre-scan) arm 12: Individuals in the anorexia nervosa group were randomized to the following scan order. Participants were administered a study medication or placebo 3 hours prior to the start of the scan. The participant did not know what study medication they received for each scan:

Scan 1: Bromocriptine (single dose, 1.25 mg, 3 hours pre-scan) Scan 2: Amisulpride (single dose, 400 mg, 3 hours pre-scan) Scan 3: Placebo(single dose, 3 hours pre-scan)
Interventions: intervention 1: amisulpride intervention 2: bromocriptine intervention 3: Placebo
Intervention descriptions: intervention 1: Dopamine D2 antagonist to test how it affects brain response and behavior to prediction error and reversal tasks during functional magnetic resonance imaging (fMRI). intervention 2: Dopamine D2 receptor agonist test how it affects brain response and behavior to prediction error and reversal tasks during functional magnetic resonance imaging (fMRI). intervention 3: Placebo pill with no active drug ingredients

Protocol documents:
Prot_SAP_000.pdf: 
 
Title: Toward understanding dopamine receptor contributions to prediction error and reversal learning in anorexia 
nervosa  
 
Protocol #191348 
 
NCT #: NCT04128683  
 
Study Protocol Date: 04/12/2021 
 
 


 
 
Biomedical IRB Application Instructions 
Page 2 
 
 
UCSD Human Research Protections Program 
New Biomedical Application 
RESEARCH PLAN 
Instructions for completing the Research Plan are available on the HRPP website. 
The headings on this set of instructions correspond to the headings of the Research Plan. 
General Instructions: Enter a response for all topic headings.  
Enter “Not Applicable” rather than leaving an item blank if the item does not apply to this project. 
Date: 04/12/2021 
1. 
PROJECT TITLE 
Toward understanding dopamine receptor contributions to prediction error and reversal learning in anorexia 
nervosa 
2. 
PRINCIPAL INVESTIGATOR  
Guido K.W. Frank, MD 
 
3. 
FACILITIES 
1. UC San Diego Health Eating Disorders Center for Treatment and Research 
2. Altman Clinical Trials Research Institute (ACTRI) 
3. Center for Advanced Laboratory Medicine (CALM) 
3. Sharp and Children’s MRI Center 
4. Medical Care San Diego 
5. LabCorp 
 
4. 
ESTIMATED DURATION OF THE STUDY 
3 years enrollment, 2 years data analysis (5 years total)  
 
5. 
LAY LANGUAGE SUMMARY OR SYNOPSIS (no more than one paragraph) 
Anorexia nervosa (AN) is an eating disorder associated with intense fear of weight gain, food refusal, and 
severe weight loss. AN has the highest mortality rate among the psychiatric disorders; however, little is known 
about biomarkers, and no medication has been approved for AN. Brain reward pathways have a direct impact 
on the drive to eat, and a variety of neuroimaging studies have suggested altered reward processing in AN. The 
neurotransmitter dopamine has a central role in the reward circuitry to drive food approach, and the dynamic 
interplay between dopamine receptor response and food restriction could have implications for the 
pathophysiology of AN. In this application, we will develop a study protocol and gather pilot data to identify 
whether specific dopamine D2 challenge drugs can modulate PE response and reversal learning in AN.  In this 
randomized placebo controlled trial we will apply a dopamine D2 receptor agonist, D2 receptor antagonist and 
placebo to healthy controls and individuals with AN to test their effects on brain reward processing and reversal 
learning. We expect that those challenge drugs will lead to opposite brain and behavioral response and directly 
support the involvement of those receptors in brain function in AN.  This research will be important to develop 
neurotransmitter specific pharmacological treatments for AN. 
 
6. 
SPECIFIC AIMS 
Aim 1. To establish in AN feasibility and acceptability of a study design to understand the 
contributions of the selective DA D2 receptor agonist bromocriptine on PE and reversal learning. 
Hypothesis 1.a. The DA D2 receptor agonist bromocriptine (1.25mg) will enhance fMRI PE response during a 
taste-reward PE paradigm in AN in ventral striatum and insula compared to placebo.  


 
 
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Hypothesis 1.b. The DA D2 receptor agonist bromocriptine (1.25mg) will enhance reversal learning and 
striatum brain response in AN during a monetary reversal learning task compared to placebo during fMRI.  
Aim 2. To establish in AN feasibility and acceptability of a study design to understand the 
contributions of the selective DA D2/D3 receptor antagonist amisulpride on PE and reversal learning.  
Hypothesis 1.a. The DA D2 receptor antagonist amisulpride (400mg) will reduce fMRI PE response in the 
insula and ventral striatum compared to placebo. 
Hypothesis 1.b. The DA D2 receptor antagonist amisulpride (400mg) will reduce reversal learning and 
striatum brain response in AN during a monetary reversal learning task compared to placebo during fMRI. 
Aim 3. To gather pilot data how fMRI brain response to the DA D2 receptor agonist bromocriptine or 
antagonist amisulpride differs between individuals with AN and healthy control women. 
Hypothesis 3. We expect we will find an indication that bromocriptine will enhance PE (ventral striatum 
and insula) and reversal learning (frontal cortex) in AN more compared to the control group, while amisulpride 
causes the opposite. 
 
7. 
BACKGROUND AND SIGNIFICANCE 
Anorexia nervosa (AN) is an eating disorder associated with intense fear of weight gain, food refusal, and 
severe weight loss (American Psychiatric Association, 2013). AN has the highest mortality rate among the 
psychiatric disorders (Sullivan, 1995; Arcelus et al., 2011), and the relapse rate is high with up to 52% (Khalsa 
et al., 2017; Berends et al., 2018). Many individuals only partially recover, and treatment options, especially for 
the psychological components of the illness, are not very effective (Berends et al., 2018; Murray et al., 2018). 
Little is known about biomarkers for AN, and no medication has been approved for AN (Simansky, 2005). 
Brain reward pathways have a direct impact on the drive to eat, and a variety of neuroimaging studies have 
suggested altered reward processing in AN (Uher et al., 2004; Fladung et al., 2010; Kaye et al., 2013b; Frank, 
2015; Monteleone et al., 2018). The neurotransmitter dopamine (DA) has a central role in the reward circuitry 
to drive food approach (Kelley et al., 2005), and the dynamic interplay between DA receptor response and food 
restriction (or overconsumption) could have implications for the pathophysiology of AN (Kelley, 2004; 
Johnson and Kenny, 2010; Carr, 2011). Recent clinical studies indicate that the DA D2 receptor partial agonist 
aripiprazole may be beneficial in the treatment of AN (Trunko et al., 2011; Frank et al., 2017). However, 
aripiprazole also acts on serotonin and other neurotransmitter receptors and whether aripiprazole’s DA D2 
receptor agonism is indeed beneficial for AN treatment is unknown (Frank, 2014). 
DA-related brain function in humans has been studied indirectly using functional magnetic resonance brain 
imaging (fMRI) and tasks that deliver reward stimuli unexpectedly, eliciting the so-called prediction error (PE) 
response (Schultz, 2002; O'Doherty et al., 2003). Research in adult AN showed elevated PE response in insula 
and striatum (Cowdrey et al., 2011; Frank et al., 2012). Studies in adolescents using monetary or taste reward 
stimuli also resulted in heightened PE responses in those regions, and orbitofrontal PE predicted weight gain in 
treatment (DeGuzman et al., 2017; Frank et al., 2018a). DA and PE response have also been associated with 
altered reversal learning (Izquierdo et al., 2017), which has important treatment implication for AN as reversal 
learning is impaired in the disorder, and modulation of the DA system could improve treatment (Wildes et al., 
2014; Allen et al., 2017; Foerde and Steinglass, 2017). Thus, the DA associated PE response promises to be an 
important biological marker for AN. 
It has been suggested that phasic DA signals encode unexpected rewards and are associated with behavioral 
activation through DA D1 receptors (Maia and Frank, 2011). On the other hand, DA D2 receptors may code the 
dip in tonic DA neuron activity when stimuli are unexpectedly omitted, and may also be involved in avoidance 
learning and behavior inhibition (Maia and Frank, 2011). Those receptor dynamics are still being investigated 
and have not been studied in AN (Soares-Cunha et al., 2016).  
In this study, we would like to use the exploratory/developmental R21 mechanism to develop a study 
protocol to gather pilot data to identify whether specific DA D2 challenge drugs are tolerated agents in the AN 


 
 
Biomedical IRB Application Instructions 
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population and whether they can modulate PE response and reversal learning in AN. This research will be 
important to develop neurotransmitter specific pharmacological treatments for AN. Studying also the DA D1 
receptor would go beyond the financial limits of this funding mechanism but will be the target of future studies. 
 
8. 
PROGRESS REPORT 
Not applicable 
 
9. 
RESEARCH DESIGN AND METHODS 
Overview of Study Procedures:   
 
In this randomized, placebo controlled trial subjects will complete a battery of self-assessments, a diagnostic 
assessment, and a pre-scan visit in order to determine eligibility. After eligibility is confirmed, subjects will be 
randomized to one of the six study arms that will determine the order in which the study medication is 
administered the morning of the MRI scans. Subjects will complete 3 MRI scans spaced approximately 3 days 
apart. Functional MRI will be performed and brain response will be measured while subjects complete a taste 
reward task and a reversal learning task. Details of the outcome measures and study procedures are listed 
below: 
 
Outcome Measure(s):   
 
Prior to completing the fMRI scans, each subject will complete the Diagnostic interviews and Self-Assessments 
listed below: 
 
 
Name 
Abbreviatio
n 
Area assessed 
 
Min
utes 
Diagnostic Interviews 
 
 
 
Structured Clinical Interview for DSM-5 
Diagnoses 
SCID 5 
Half structured diagnostic 
interview for Axis I Disorders 
45-
90 
Self-assessments (Questionnaire Packet) 
 
 
 
 
Spielberger State-Trait Anxiety Scale-Version 
Y 
STAI-Y 
State and trait anxiety 
10 
 
Beck Depression Inventory 
BDI-II 
Assess the cognitive, behavioral, 
affective, and somatic symptoms 
associated with depression. 
5 
 
Eating Expectancy Inventory 
EEI 
Measures cognitive expectations 
for eating 
5 
 
Food Cravings Questionnaire - Trait 
FCQ-T 
Measures intensity of state and trait 
food cravings 
10 
 
Intolerance of Uncertainty Scale 
IUS 
Measures intolerance of 
uncertainty 
5 
 
Eating Disorder Examination  
EDE-Q 
Measures restraint and eating, 
weight and 
shape concern 
15 


 
 
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Temporal Experience of Pleasure Scale 
TEPS 
Measures anticipatory and 
consummatory experiences of 
pleasure for food and nonfood 
items 
5 
 
Eating Disorders Inventory -3  
EDI-3 
Core ED symptoms  
15 
 
Temperament and Character Inventory 
TCI 
Personality and temperament 
30 
 
Sensitivity to Punishment and Sensitivity to 
Reward Questionnaire 
SPSRQ 
Reward and Punishment 
Sensitivity 
5 
 
Beck Cognitive Insight Scale 
BCIS 
Subject beliefs and degree of 
confidence in beliefs 
5 
 
Schedule for Assessment of Insight – 
Modification for Eating Disorders 
SAI-ED 
Insight into eating disorder 
symptoms 
3 
 
Behavioral Inhibition Scale/Behavioral 
Activation Scale 
BIS/BAS 
Reward and Punishment 
Sensitivity 
5 
 
Parental Bonding Instrument  
PBI 
Parental bonding 
5 
 
Adverse Childhood Effects Questionnaire 
ACEs 
Childhood trauma 
5 
Scan Day Assessments  
 
 
 
 
Food Cravings Questionnaire - State 
FCQ-S  
Measures intensity of state and trait 
food cravings 
5 
 
Hedonic Taste Preference Scale for 
Sweet Stimuli 
HTP
S 
Sweet taste pleasantness & 
sweetness ratings 
5 
 
Taste Labeled Magnitude Scale 
LMS 
Taste sensation ratings 
2 
 
Post Scan Taste Ratings 
 
Scan solutions taste 
pleasantness & sweetness 
ratings 
2 
 
Post MRI Questionnaire 
 
Questions about pre-scan 
behaviors & problems 
during scan 
5 
 
The Positive and Negative Affect 
Schedule 
PAN
AS 
Measures current mood 
states, completed Pre-Scan, 
Post Scan and Post Meal 
5 
 
Eating Expectancy Inventory 
EEI 
Measures cognitive expectations 
for eating 
5 
 
Beck Depression Inventory 
BDI-II 
Assess the cognitive, behavioral, 
affective, and somatic symptoms 
associated with depression. 
5 
 
Eating Disorder Examination  
EDE-Q 
Measures restraint and eating, 
weight and 
shape concern 
15 
 
Temporal Experience of Pleasure Scale 
TEPS 
Measures anticipatory and 
consummatory experiences of 
pleasure for food and nonfood 
items 
5 
 
In addition to completing these measures, subjects will complete 3 fMRI scans.  While in the MRI scanner, 
subjects will complete a Taste Reward Task and a Reversal Learning Task (described below).    


 
 
Biomedical IRB Application Instructions 
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Study Procedures Chart (Subjects from Community) 
 
 
  
Initial 
Phone 
Screen 
Detailed 
Eligibility 
Screen 
Screening 
Visit 
Pre-Scan 
Visit 
Study 
Visit 1 
Study 
Visit 2 
Study 
Visit 3 
Initial 
Screening 
X 
  
  
  
  
  
  
Informed 
Consent 
(through mail) 
  
X 
  
  
  
  
  
Questionnaire 
Packet 
  
X 
  
  
  
  
  
Biological 
Screening 
Form 
  
X 
  
  
  
  
  
In person 
Consent and 
Interview with 
PI 
  
  
X 
  
  
  
  
Diagnostic 
Interview 
  
  
X 
  
  
  
  
Swallow Test 
 
 
X 
 
 
 
 
Blood Tests & 
EKG 
  
  
  
X 
  
  
  
Pregnancy 
Test 
  
  
  
  
X 
  
  
Taste Test 
  
  
  
  
X 
X 
X 
MRI Scan 
  
  
  
  
X 
X 
X 
Scan 
Questionnaires   
  
  
  
X 
X 
X 
 
 
 
 
Study Procedures Chart (Subjects from UC San Diego Health Eating Disorders Center for Treatment 
and Research) 
 
  
Consent 
Visit 
Screening 
Visit 
Pre-Scan 
Visit 
Study 
Visit 1 
Study 
Visit 2 
Study 
Visit 3 
Initial 
Screening 
X 
  
  
  
  
  


 
 
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Informed 
Consent 
X 
  
  
  
  
  
Questionnai
re Packet 
  
X 
  
  
  
  
Consent and 
Interview 
with PI  
  
X 
  
  
  
  
Diagnostic 
Interview 
  
X 
  
  
  
  
Swallow 
Test 
 
X 
 
 
 
 
Blood Tests 
& EKG 
  
  
X 
  
  
  
Pregnancy 
Test 
  
  
  
X 
  
  
Taste Test 
  
  
  
X 
X 
X 
MRI Scan 
  
  
  
X 
X 
X 
Scan 
Questionnai
res 
  
  
  
X 
X 
X 
 
 
 
 
TIMELINE 
 
Subjects from the Community 
 
Screening Visit  
Location: PI office at UC San Diego Health Eating Disorders Center for Treatment and Research (4510 
Executive Dr, Suite 330) 
 
Subjects who meet eligibility criteria based on the results of the questionnaires and phone bioscreen will be 
invited to the in-person interview with the PI at the UC San Diego Health Eating Disorders Center for 
Treatment and Research. At the start of the study visit, the PI or research coordinator will review the consent 
form with the subject, will answer any questions about the study and will assess comprehension of the study 
procedures, benefits, and risks. Subjects will then sign a new consent form and a signed and dated copy of the 
completed consent form will be given to the subject.  
 
Dr. Frank will meet with each subject to complete the diagnostic assessment (SCID-5) and comprehensive 
medical interview with the subject to determine study eligibility.  
 
After eligibility is confirmed, the subject will complete a swallow test where she will be given an empty pill 
capsule and will be asked to swallow to make sure she will not have any issues with the size of the medication 
capsules. If the subject cannot swallow this size capsule or feels she will not be able to, she may be withdrawn 
from the study at that point.  
 


 
 
Biomedical IRB Application Instructions 
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The subject will be scheduled for the Pre-Scan Visit and 3 MRI scans. The MRI scans will be scheduled 2 to 4 
days apart (3 days apart is ideal).  
 
Pre-Scan Visit 
Location: Altman Clinical Trials Research Center (9452 Medical Center Dr) 
 
 
Subjects will complete a pre-scan visit at ACTRI to complete a blood draw and electrocardiogram (EKG). This 
visit will occur no more than 1 week before Study Visit 1 is scheduled. At this visit ACTRI research nursing 
staff (certified phlebotomist) will complete the blood draw (about 2 tablespoons blood). An EKG will be 
performed, and results of the EKG and blood tests will be sent to the PI for review. The following tests will be 
processed through the Center for Advanced Laboratory Medicine (CALM): Creatinine; BUN; electrolytes; 
serum pregnancy test. If the PI feels the results are out of range he may withdraw the subject from the study.  
 
Alternatively, subjects may complete the Electrocardiogram (EKG) at Medical Care San Diego (7634 Girard 
Ave Ste A, La Jolla) and the labs (Creatinine, BUN, electrolytes and serum pregnancy test) at either the 
Medical Care San Diego (7634 Girard Ave Ste A, La Jolla) or a LabCorp location close to where the subject 
resides. Subjects who use these facilities to complete the EKG and labs will provide the PI and his staff with 
the test results. Subjects will need to complete these tests no more than one week prior to the first scheduled 
MRI scan. The research study will pay these facilities directly on the subject’s behalf with the self-pay option. 
Once the PI receives the test results, if he feels the results are out of range he may withdraw the subject from 
the study.  
 
Study Visit 1 
Location: Sharp and Children’s MRI Center (7910 Frost St) 
 
The morning of the imaging procedures the subject will go to the Sharp and Children’s MRI Center for the 
scanning procedures. The medication will need to be administered 3 hours before the start of the scan.  
 
When the subject arrives at the MRI Center, subjects will complete a urine pregnancy test. After the pregnancy 
test (test must be negative), the research assistant will take the subject’s blood pressure and measure her heart 
rate and administer the study medication. The subject will complete the Taste Labeled Magnitude Scale, 
Hedonic Taste Preference Scale, Food Cravings Questionnaire (State), Eating Disorders Examination (EDE-Q), 
Temporal Experience of Pleasure Scale (TEPS), Eating Expectancy Inventory (EEI), Beck Depression 
Inventory (BDI-II), The Positive and Negative Affect Schedule (PANAS), and eat a standardized breakfast.  
 
The research staff will then review study procedures and fMRI tasks.  
 
Subjects will then complete the fMRI and structural MRI (details of tasks outlined below).  
 
After the scan, the research assistant will take the subject’s blood pressure and heart rate and will have the 
subject complete the Post Scan Pleasantness Ratings and the Post MRI Questionnaire.  
 
The total length of the study visit will be approximately 4 hours (3 hours pre-scan, 1 hour scan). 
 
 
Study Visit 2 
Location: Sharp and Children’s MRI Center (7910 Frost St) 
 


 
 
Biomedical IRB Application Instructions 
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The morning of the imaging procedures the subject will go to the Sharp and Children’s MRI Center for the 
scanning procedures. The medication will need to be administered 3 hours before the start of the scan.  
 
When the subject arrives at the MRI Center, the research assistant will take the subject’s blood pressure and 
measure her heart rate and administer the study medication. The subject will complete the Taste Labeled 
Magnitude Scale, Hedonic Taste Preference Scale, Food Cravings Questionnaire (State), Eating Disorders 
Examination (EDE-Q), Temporal Experience of Pleasure Scale (TEPS), Eating Expectancy Inventory (EEI), 
Beck Depression Inventory (BDI-II), The Positive and Negative Affect Schedule (PANAS), and eat a 
standardized breakfast.  
 
The research staff will then review study procedures and fMRI tasks.  
 
Subjects will then complete the fMRI and structural MRI (details of tasks outlined below).  
 
After the scan, the research assistant will take the subject’s blood pressure and heart rate and will have the 
subject complete the Post Scan Pleasantness Ratings and the Post MRI Questionnaire.  
 
The total length of the study visit will be approximately 4 hours (3 hours pre-scan, 1 hour scan). 
 
 
Study Visit 3 
Location: Sharp and Children’s MRI Center (7910 Frost St) 
 
 
The morning of the imaging procedures the subject will go to the Sharp and Children’s MRI Center for the 
scanning procedures. The medication will need to be administered 3 hours before the start of the scan.  
 
When the subject arrives at the MRI Center, the research assistant will take the subject’s blood pressure and 
measure her heart rate and administer the study medication. The subject will complete the Taste Labeled 
Magnitude Scale, Hedonic Taste Preference Scale, Food Cravings Questionnaire (State), Eating Disorders 
Examination (EDE-Q), Temporal Experience of Pleasure Scale (TEPS), Eating Expectancy Inventory (EEI), 
Beck Depression Inventory (BDI-II), The Positive and Negative Affect Schedule (PANAS), and eat a 
standardized breakfast.  
 
The research staff will then review study procedures and fMRI tasks.  
 
Subjects will then complete the fMRI and structural MRI (details of tasks outlined below).  
 
After the scan, the research assistant will take the subject’s blood pressure and heart rate and will have the 
subject complete the Post Scan Pleasantness Ratings and the Post MRI Questionnaire.  
 
The total length of the study visit will be approximately 4 hours (3 hours pre-scan, 1 hour scan). 
 
 
Subjects from UC San Diego Health Eating Disorders Center for Treatment and Research 
 
Consent Visit (Subjects from UC San Diego Health Eating Disorders Center for Treatment and 
Research) 


 
 
Biomedical IRB Application Instructions 
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Location: UC San Diego Health Eating Disorders Center for Treatment and Research (4510 Executive 
Drive, Suite 315) 
 
Subjects from these programs who are interested in the study will be scheduled to meet with a research staff 
member. Research staff and the PI will screen EPIC charts for potential subjects from UC San Diego Health 
Eating Disorders Center for Treatment and Research to determine initial eligibility. Prior to approaching the 
patient, Dr. Frank and/or his staff will obtain permission from the patient’s individual therapist prior to making 
contact with the patient to describe the research opportunity. 
 
The research staff will meet with each subject at UC San Diego Health Eating Disorders Center for Treatment 
and Research and go over initial eligibility. The research staff will review the consent form and study 
procedures with each subject, assess comprehension of study procedures, benefits and risks, and answer 
questions about the study.  
 
A signed and dated copy of the completed consent form will be given to the subject.  
 
Dr. Frank or a PhD level clinician will meet with each subject to complete the diagnostic assessment (SCID-5) 
and comprehensive medical interview with the subject to determine study eligibility.  
 
After eligibility is confirmed, the subject will complete a swallow test where she will be given an empty pill 
capsule and will be asked to swallow to make sure she will not have any issues with the size of the medication 
capsules. If the subject cannot swallow this size capsule or feels she will not be able to, she may be withdrawn 
from the study at that point.  
 
The subject will be scheduled for the Pre-Scan Visit and 3 MRI scans. The MRI scans will be scheduled 2 to 4 
days apart (3 days apart is ideal).  
 
Pre-Scan Visit 
Location: Altman Clinical Trials Research Center (9452 Medical Center Dr) 
 
 
Subjects will complete a pre-scan visit at ACTRI to complete a blood draw and electrocardiogram (EKG). This 
visit will occur no more than 1 week before Study Visit 1 is scheduled. At this visit ACTRI research nursing 
staff (certified phlebotomist) will complete the blood draw (about 2 tablespoons of blood). The following tests 
will be run at the CALM facility: Creatinine; BUN; electrolytes; serum pregnancy test. An EKG will be 
performed at the ACTRI, and results of the EKG and blood tests will be sent to the PI for review. If the PI feels 
the results are out of range he may withdraw the subject from the study.  
 
Alternatively, subjects may complete the Electrocardiogram (EKG) at Medical Care San Diego (7634 Girard 
Ave Ste A, La Jolla) and the labs (Creatinine, BUN, electrolytes and serum pregnancy test) at either the 
Medical Care San Diego (7634 Girard Ave Ste A, La Jolla) or a LabCorp location close to where the subject 
resides. Subjects who use these facilities to complete the EKG and labs will provide the PI and his staff with 
the test results. Subjects will need to complete these tests no more than one week prior to the first scheduled 
MRI scan. The research study will pay these facilities directly on the subject’s behalf with the self-pay option. 
Once the PI receives the test results, if he feels the results are out of range he may withdraw the subject from 
the study.  
 
 
Study Visit 1 


 
 
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Location: Sharp and Children’s MRI Center (7910 Frost St) 
 
 
The morning of the imaging procedures the subject will go to the Sharp and Children’s MRI Center for the 
scanning procedures. The medication will need to be administered 3 hours before the start of the scan.  
 
When the subject arrives at the MRI Center, subjects will complete a urine pregnancy test. After the pregnancy 
test (test must be negative), the research assistant will take the subject’s blood pressure and measure her heart 
rate and administer the study medication. The subject will complete the Taste Labeled Magnitude Scale, 
Hedonic Taste Preference Scale, Food Cravings Questionnaire (State), Eating Disorders Examination (EDE-Q), 
Temporal Experience of Pleasure Scale (TEPS), Eating Expectancy Inventory (EEI), Beck Depression 
Inventory (BDI-II), The Positive and Negative Affect Schedule (PANAS), and eat a standardized breakfast.  
 
The research staff will then review study procedures and fMRI tasks.  
 
Subjects will then complete the fMRI and structural MRI (details of tasks outlined below).  
 
After the scan, the research assistant will take the subject’s blood pressure and heart rate and will have the 
subject complete the Post Scan Pleasantness Ratings and the Post MRI Questionnaire.  
 
The total length of the study visit will be approximately 4 hours (3 hours pre-scan, 1 hour scan). 
 
 
Study Visit 2 
Location: Sharp and Children’s MRI Center (7910 Frost St) 
 
 
The morning of the imaging procedures the subject will go to the Sharp and Children’s MRI Center for the 
scanning procedures. The medication will need to be administered 3 hours before the start of the scan.  
 
When the subject arrives at the MRI Center, the research assistant will take the subject’s blood pressure and 
measure her heart rate and administer the study medication. The subject will complete the Taste Labeled 
Magnitude Scale, Hedonic Taste Preference Scale, Food Cravings Questionnaire (State), Eating Disorders 
Examination (EDE-Q), Temporal Experience of Pleasure Scale (TEPS), Eating Expectancy Inventory (EEI), 
Beck Depression Inventory (BDI-II), The Positive and Negative Affect Schedule (PANAS), and eat a 
standardized breakfast.  
 
The research staff will then review study procedures and fMRI tasks.  
 
Subjects will then complete the fMRI and structural MRI (details of tasks outlined below).  
 
After the scan, the research assistant will take the subject’s blood pressure and heart rate and will have the 
subject complete the Post Scan Pleasantness Ratings and the Post MRI Questionnaire.  
 
The total length of the study visit will be approximately 4 hours (3 hours pre-scan, 1 hour scan). 
 
 
Study Visit 3 
Location: Sharp and Children’s MRI Center (7910 Frost St) 


 
 
Biomedical IRB Application Instructions 
Page 12 
 
 
The morning of the imaging procedures the subject will go to the Sharp and Children’s MRI Center for the 
scanning procedures. The medication will need to be administered 3 hours before the start of the scan.  
 
When the subject arrives at the MRI Center, the research assistant will take the subject’s blood pressure and 
measure her heart rate and administer the study medication. The subject will complete the Taste Labeled 
Magnitude Scale, Hedonic Taste Preference Scale, Food Cravings Questionnaire (State), Eating Disorders 
Examination (EDE-Q), Temporal Experience of Pleasure Scale (TEPS), Eating Expectancy Inventory (EEI), 
Beck Depression Inventory (BDI-II), The Positive and Negative Affect Schedule (PANAS), and eat a 
standardized breakfast.  
 
The research staff will then review study procedures and fMRI tasks.  
 
Subjects will then complete the fMRI and structural MRI (details of tasks outlined below).  
 
After the scan, the research assistant will take the subject’s blood pressure and heart rate and will have the 
subject complete the Post Scan Pleasantness Ratings and the Post MRI Questionnaire.  
 
The total length of the study visit will be approximately 4 hours (3 hours pre-scan, 1 hour scan). 
 
fMRI Study Procedures 
Location: Sharp and Children’s MRI Center (7910 Frost St) 
 
Experimental arrangements before experiment Procedure:  All subjects will come to the Sharp & 
Children’s MRI Center between 6 and 7 am (or 3 hours prior to the start of the scan). Subjects will have a urine 
pregnancy test (Study Visit 1 only), and all will receive a standardized breakfast and complete scan day 
questionnaires.  
 Taste fMRI – Expected and Unexpected sweet stimulus: In this study, subjects will get small samples (1.0 
cc) of fluid that will consist of Sucrose or neutral solution (artificial saliva). These fluid samples will be 
administered through food grade polyethylene plastic tubes (1/8 inches inner, 3/16 inches outer diameter, 
FDA/USDA approved, Cole-Parmer, Vernon Hill, IL) that subjects hold in their mouth. In addition, the 
subjects will be trained to perform one tongue motion after each application of taste stimulant in order to wash 
the taste stimuli around the mouth and stimulate taste buds. The fluid will be released, at intervals, by a pump 
mechanism. Because of the small volume of fluid, there is no danger of aspiration. The subjects will be able to 
swallow the small amounts of solutions after application.  Subjects that are not capable of carrying out these 
required procedures will be excluded from the study.  
Syringe Pump Assembly: Fluid challenges will be delivered to the subject by an apparatus (Figure 3.1.) that 
will use a semi-automatic and programmable customized syringe pump (J-Kem Scientific, St. Louis, MO).   
The syringe pump will pump samples from 5 reservoirs through FDA approved food grade teflon tubes (Cole-
Parmer, Vernon Hills, IL; see above)  into the subject’s mouth.  The reservoir tube and the tube to the subject 
are connected via a 2 way Teflon valve enabling the syringe pump to draw solution from the desired reservoir 
into the glass syringes that are part of the syringe pump mechanism.  The valve at the syringe pump will switch 


 
 
Biomedical IRB Application Instructions 
Page 13 
direction depending on if the pump refills the syringes or pumps solution to the subject. For solution delivery, 
the tastant is then pressed into the Teflon tubes that are directed toward the subject. The delivering tubes are 
approximately 10 meters (m) in length and will be pre-filled with sample solutions so that 1.0cc of solution can 
be administered to the subject in 1 second. There will be 3 seconds between samples during which fMRI 
scanning will be performed. The syringe pump will be located in the MRI-technician room, and the tubing to 
the subject will run from the pump to the subject in the MRI scanner room through a port in the wall of the 
MRI scanning room. The syringe pump’s hardware will be connected to a Laptop PC (Dell600, Dell, USA) in 
the technician room. This PC will control the rate of administration of the solution and the solution choice and 
will also be the interface between taste application/syringe pump and the MRI scanner control panel.  We will 
use E-Prime (Psychology Software Tools, Inc., Pittsburgh, PA) software in order to coordinate the taste 
stimulation and fMRI scanning procedure.  
 
 
Method of Taste Application 
This design will be closely modeled after the design used by O’Doherty et al (O'Doherty et al., 2003). Each trial 
will consist of the presentation of one of five arbitrary visual stimuli (which will be abstract fractals, see Figure 
3.2; we established contact with O’Doherty’s group and received fractals originally used in this paradigm) 
followed 3 s later by either 1 ml of a pleasant sweet taste (1 M sucrose) (CS+), a neutral taste (CSneut: 25mM 
KCl, 2mM NaHCO3, (Francis et al., 1999, Frank et al., 2003)) or no taste (CS-). The visual stimuli will be 
presented on a gray background and will be removed from the screen after 3 s to coincide with taste delivery. A 
fixation cross will then be presented for the remainder of the trial. After a further 3 s, the next trial will be 
scheduled. The allocation of each stimulus to a given trial type will be counterbalanced across subjects. There 
will be a total of 280 trials in the experiment, 100 each of CS+ and CS- and 80 of CSneut. The whole 
experiment will last a total of ~28.5 min. After the first ten CS+ stimuli that will be presented and paired on 
each occasion with reward, in 20 out of 90 subsequent CS+ presentations, the reward will be omitted (CS+ 
omit). Further, in 20 presentations of the CS-, a reward will be unexpectedly delivered (CS- unexpected). The 
CSneut condition will be primarily included to provide a low valence rinse for the glucose taste during the 
experiment. The order of presentation of events will be randomized and presented to subjects using E-Prime 
(Psychology Software Tools, Pittsburgh, PA).  


 
 
Biomedical IRB Application Instructions 
Page 14 
 
 
fMRI Design 
 
Taste Reward Task: An event-related design will be used. The fMRI variables of interest are percent 
signal difference after: 1) taste stimulus within subject groups and across taste stimulus types, 2) within subject 
groups and stimulus type across expected and received vs. expected but not received stimulus, and 3) across 
groups within stimulus types and conditions as above. 
  
Acquisition of images: Studies will be performed with at 3T GE MR system (GE Healthcare, 
Milwaukee, WI) using a standard quadrate head coil. A high-resolution, T1-weighted 3 D anatomical scan will 
be acquired for each subject (IR-SPGR, TR=9 ms, TE=1.9 ms, TI=500 ms flip angle=10°, matrix= 256×256, 
FOV=220 mm2, 124 1.7 mm thick coronal slices) for coregistration to functional data. Functional images were 
acquired with a gradient-echo T2 Blood Oxygenation Level Dependent (BOLD) contrast technique, with 
TR=14000 ms (as a clustered volume acquisition of 2000 ms, plus an additional 12000 ms silent interval), 
TE=30 ms, FOV=220 mm2, 642 matrix, 31 slices, 4 mm thick, no gap, angled parallel to the planum 
sphenoidale. Additionally, one IR-EPI (TI=505 ms) volume was acquired to improve coregistration between 
EPIs and the IR-SPGR. Head motion will be minimized with a VacFix headconforming vacuum cushion (Par 
Scientific A/S, Odense, Denmark). MR-compatible goggles (Resonance Technology, Inc, CA, USA) will be 
used for visual stimuli. 
fMRI Image Analysis Pathway: Images will be preprocessed and analyzed using SPM12 
(www.fil.ion.ucl.ac.uk/spm/). Images will be realigned to the first volume, normalized to the Montreal 
Neurological Institute template, smoothed at 6mm full width at half maximum Gaussian kernel. Data will be 
preprocessed with slice time correction and modeled with a hemodynamic response convolved function using 
the general linear model, including temporal and dispersion derivatives. A 128-second high-pass filter will be 
applied for low-frequency BOLD signal fluctuations, and motion parameters as first-level analysis regressors.  
Description of how hypotheses will be tested, including neurocomputational modeling approaches. This 
study tests the brain response in controls compared to ILL AN women. The paradigm will test reward-learning 
related brain activation in response to taste stimuli.  There will be a primary and a secondary analysis pathway 
in the paradigm. 
The primary analysis pathways will use the methods described in the above fMRI analysis pathway sections. 
For the taste paradigm this primary analysis will identify brain region activation in response to the conditioned 
fractal or unconditioned sweet taste application as well as brain response when no taste is received but 
expected. Main effect results will be obtained for condition and subject group, as well as time activity curve 


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Biomedical IRB Application Instructions 
Page 16 
presented. One of the patterns is “correct”, and the other pattern is “wrong”. Using trial-and-error feedback, 
subjects must discover which of the two patterns is correct, using the left or right button on a button response 
box. On each trial, the stimuli are presented for 2000 msec within which the response has to be made. 
Feedback, consisting of a green smiley face and “win $1” for correct responses or a red sad face and “lose $1” 
for incorrect responses, will be presented immediately after the response. After feedback, the stimuli will be 
removed and the faces replaced by a fixation cross for a variable interval (average inter-stimulus interval is 
3200 msec). Each block consists of 10 discrimination stages, and therefore, 9 reversal stages. Reversal of the 
stimulus-reward contingency occurs after between 10 and 15 correct responses (including probabilistic errors). 
The number of probabilistic errors between each reversal varies from 0 to 4. To prevent subjects from adopting 
a strategy such as always reversing after two consecutive errors, probabilistic negative feedback is given on two 
consecutive trials once during each task block. Each block lasts about 8.5 min, total number of blocks is three.  
Reversal Learning Task Data Modeling. The following contrasts will be modeled: (1) final reversal error trials 
minus correct responses, (2) other preceding reversal error trials minus correct responses, (3) probabilistic error 
trials minus correct responses, (4) final reversal error trials minus other preceding reversal errors, and (5) final 
reversal error trials minus probabilistic errors (Cools et al., 2002). 
 
Dopamine Challenge Drugs Amisulpride and Bromocriptine 
Amisulpride. Amisulpride (4-amino-N-[(1-ethylpyrrolidin-2-yl)methyl]-5-ethylsulfonyl-2-methoxy-benzamide 
has a bioavailability of 48% and a half-life of about 12 hours (Rosenzweig et al., 2002). It binds selectively 
(https://pubchem.ncbi.nlm.nih.gov/compound/2159) to DA D(2) and D(3) receptors in the limbic system. It 
reaches its peak plasma levels after 1 hour and has a second peak after 3 hours. Amisulpride does not have 
active metabolites (Bergemann et al., 2005). Low doses of amisulpride block presynaptic D(2)/D(3)-dopamine 
autoreceptors, thereby enhancing dopaminergic transmission, whereas higher doses block post-synaptic 
receptors, thus inhibiting DA activity (Leucht et al., 2002). In this application, we will apply a high dose to take 
advantage of the DA D2 receptor blocking effects of amisulpride. We are orienting our dosing on previous 
research using a single dose of 400mg amisulpride to block post-synaptic DA D2 receptors during fMRI (Kahnt 
and Tobler, 2017). That dosage showed good tolerability (Rosenzweig et al., 2002). Whether this dose is 
tolerable in an AN population has not been established and is a goal of this study. Establishing 
pharmacokinetics with plasma levels will also be important but will be part of future larger studies. 
Bromocriptine. Bromocriptine is a semisynthetic, ergot alkaloid with anti-Parkinson and lactation inhibitory 
activities. Bromocriptine selectively binds to and activates postsynaptic DA D2-like receptors in the central 
nervous system (CNS), its half-life is between 2 and 8 hours, and it does not have active metabolites 
(https://pubchem.ncbi.nlm.nih.gov/compound/31101). Bromocriptine has a bioavailability of 28% and reaches 
its peak plasma level around 3 hours after ingestion (Holt et al., 2010). Bromocriptine has been used in fMRI 
previously and modulated reward and reversal learning (Cools et al., 2009). Effects of DA synthesis capacity 
will be tested in future larger studies. We will apply a single dose of 1.25mg bromocriptine, which was 
effective in manipulating both fMRI and behavior results (Cools et al., 2009; Lissek et al., 2018). 
Special Pharmacological Considerations. Bromocriptine is an anti-Parkinson medication available in the US. 
An investigational new drug (IND) application to the Federal Drug Administration (FDA) has been approved, 
IND # 141908. Amisulpride is an antipsychotic not freely available in the US; however, it can be purchased via 
Sanofi France as in previous studies (Admon et al., 2017). We have received an IND from the FDA, which 
allows for legal import of amisulpride. Both medications have a plasma peak of 3 hours, and fMRI will begin 
for all sessions at that time point after taking active drug or placebo. The half-lives for amisulpride of 12 hours, 
and 2-8 hours for bromocriptine are short enough to allow 3 days in between studies to suffice the 5 half-lives 


 
 
Biomedical IRB Application Instructions 
Page 17 
rule for medication elimination from the body (neither medication has active metabolites) (Bergemann et al., 
2005; Holt et al., 2010; Schatzberg and Nemeroff, 2013).  
Handling of Study Medication 
Storage Location: UC San Diego Health Eating Disorders Center for Treatment and Research, 4510 
Executive Drive, Suite 206, Rm 2-507 (PI Office, Guido K.W. Frank) 
Medications will be stored in a locked cabinet in the research office of the PI. That office is embedded in the 
UC San Diego Health Eating Disorders Research Program office suite, which is locked. Each study drug will 
be labeled with the statement “Caution: New Drug—Limited by Federal (or United States) law to 
investigational use.” (§312.6   Labeling of an investigational new drug.).  
 
A randomization protocol will be developed ahead of the study using Research Randomizer 
(https://www.randomizer.org). The PI will randomize the study days for the three medications. A master file 
with the randomization of medication per subject will be kept by the study monitor (Dr. Bryan Tolliver). 
 
While the tablets look slightly different, subjects will not be told what type of medication they receive on either 
day. Study participants have been drug naïve to any of the study medications, and we do not expect recognition. 
It is uncertain what specific effects each medication will have on brain function and there will therefore be no 
implicit bias.  
Each subject will complete three MRI scan days (Study Visit 1, Study Visit 2, and Study Visit 3). On each day, 
the subject will consume one of the three medications (amisulpride, bromocriptine or placebo).  Each subject 
will complete a baseline scan (P-fMRI), Amisulpride scan (A-fMRI), and Bromocriptine scan (B-fMRI) spaced 
3 days apart (2 to 4 day acceptable range). This randomized study has 6 medication study arms listed below:  
On the morning of each study day, the PI or other study staff not running the fMRI scanning procedures will 
provide the study subjects the medication as per randomization. Other study personnel that will run the fMRI 
scanning procedures will be kept blinded from the applied medication. This will help reduce bias by the study 
personnel. 
 
There are no rater applied assessments on the study days so there is no rater bias based on the personnel end. 
The fMRI data are objective and thus unbiased.  
 
The investigator will not supply the investigational drug to any person not authorized under this part to receive 
it. (§312.61 Control of the investigational drug.) 
 
Neither study drug is a controlled substance. Nevertheless, the study medication packages with the 
investigational drugs will be in a securely locked, substantially constructed cabinet, in the PI’s office, which is 
within an office suite that is locked and accessible only to the research personnel.  
Should the subject have a serious adverse reaction that required emergency treatment, the PI would be 
contacted and the blinding of the medication order would be broken in order to allow adequate treatment of the 
patient by emergency department staff.  
Each subject will be randomized to one of the following groups:  
1.  


 
 
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Scan 1: P-fMRI 
Scan 2: A-fMRI 
Scan 3: B-fMRI 
 
2.  
Scan 1: P-fMRI 
Scan 2: B-fMRI 
Scan 3: A-fMRI 
 
3.  
Scan 1: A-fMRI 
Scan 2: P-fMRI 
Scan 3: B-fMRI 
 
4.  
Scan 1: A-fMRI 
Scan 2: B-fMRI 
Scan 3: P-fMRI 
 
5.  
Scan 1: B-fMRI 
Scan 2: P-fMRI 
Scan 3: A-fMRI 
 
6.  
Scan 1: B-fMRI 
Scan 2: A-fMRI 
Scan 3: P-fMRI 
 
Medication dosage 
Amisulpride – Single Dose 400 mg and scan 3 hours post ingestion 
Bromocriptine – Single Dose 1.25 mg and  scan 3 hours post ingestion 
Amisulpride 
Contraindications: Amisulpride’s use is contraindicated in the following disease states: Pheochromocytoma, 
concomitant prolactin-dependent tumors (e.g. breast cancer), movement disorders (e.g. Parkinson’s Disease) 
and lactation. Subjects will be screened during the interview with the PI to ensure they do not have any of these 
conditions that are contraindicated.  
Potential side effects during ongoing use include fever, excessive sweating, change in heart rate, chest pain, 
swelling, pain, and redness in the legs, increased frequency of infections, skin allergy, seizures, restless legs, 
twitches in the tongue and face, trembling, excessive salivation, constipation, decreased libido, weight gain, 
amenorrhea, gynecomastia, agitation and anxiety, tardive dyskinesia and neuroleptic malignant syndrome.  


 
 
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However, we will only include drug naïve individuals and the one-time application has been well tolerated in 
previous studies and we do not expect problems other than maybe nausea, which will be discussed as part of the 
IRB consent process (Rosenzweig et al., 2002). 
Amisulpride has been used in similar ways in brain imaging research. 
We expect to see if at all some nausea. The other side effects are in the context of prolonged prescription and 
not after single dose.  
Subject Stopping criteria: 
If a subject were to feel so nauseous she cannot perform the study it will be stopped. If there are any other 
symptoms that interferes with subjects’ normal functioning we will stop the study. 
Bromocriptine  
Contraindications: This medication is contraindicated in syncopal migraines, uncontrolled hypertension, 
pheochromocytoma, prolactinoma, breast cancer, hypersensitivity/allergy to bromocriptine. Participants with a 
history of long QT syndrome or family history of sudden death or long QT syndrome will be exclusion criteria. 
A history of seizures or seizure disorder is an exclusion criterion. Subjects will be screened during the interview 
with the PI to ensure they do not have any of these conditions that are contraindicated.  
Bromocriptine is a dopamine D2 receptor agonist for the treatment of Parkinson's Disease and Type 2 Diabetes.  
The medication's potential common side effects for ongoing use as per the manufacturer include nausea, 
headache, stomach upset, dizziness, drowsiness, feeling faint, fainting, suddenly falling asleep. Serious side 
effects can include heart attack, stroke, pulmonary fibrosis. 
Individuals whoever took the medication before will be excluded, and the one-time application should at most 
be associated with nausea, headache or dizziness (Diederen et al., 2017). For each study participant only a one-
time application is planned, just prior to brain imaging. The objective is to enhance dopamine transmission in 
the brain. We will only include drug naïve individuals and the one-time application has been well tolerated in 
previous studies and we do not expect problems other than maybe nausea, which will be discussed as part of the 
IRB consent process. 
Bromocriptine has been used in similar ways in brain imaging research. 
Subject Stopping criteria: If a subject were to feel so nauseous or dizzy that she cannot perform the study it 
will be stopped. If there are any other symptoms that interferes with subjects’ normal functioning we will stop 
the study.   
 
Study Duration 
Altogether, assessments will take about 3 hours, the Pre-Scan blood draw and EKG will take about an hour and 
each brain imaging session including breakfast, medication administration and pre-scan questionnaires will take 
about 4 hours.  Total study duration therefore is about 16 hours. 
 


 
 
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Clinical Procedures and Interventions: Not applicable, all procedures are research related, no standard of 
care procedures or treatment provided. 
 
Drugs & Devices 
 
Administration of Drugs: The drugs amisulpride (400 mg) and bromocriptine (1.25 mg) will be administered 
in study, 3 hours prior to the MRI scan. Both drugs are investigational drugs and the PI, Dr. Frank, has 
submitted and received approval from the FDA for this study (IND # 141908, see attached approval letter)  
 
Associated Devices:  
• MRI scans will be performed on a GE Discovery MR 750 3.0 T Scanner (see attached 510(k) FDA 
approval document (Discovery MR750 FDA Approval - K142361.pdf) 
 
• EKG will be performed at the Altman Clinical Trials Research Institute.  
 
Research Facilities and Research Procedures Performed at Facility 
 
1. UC San Diego Health Eating Disorders Center for Treatment and Research: PI/Research Staff offices, 
subject recruitment, data storage, data analysis, consent visits, storage of medication.  
 
2. Altman Clinical Trials Research Center (ACTRI): Pre-Scan Visit (blood draw and EKG, primary option). 
 
3. Center for Advanced Laboratory Medicine (CALM): Blood test processing (serum pregnancy test, BUN, 
Creatinine, Electrolytes). 
4. Sharp and Children’s MRI Center: Study Visit 1, Study Visit 2, Study Visit 3 
 
5. Medical Care San Diego: Pre-Scan Visit (blood draw and EKG, secondary option from ACTRI) 
 
6. LabCorp: Pre Scan Visit (blood draw, secondary option from ACTRI) 
 
Inclusion of Women and Minorities 
 
Inclusion of Women: This project will study females with anorexia nervosa (AN) and healthy controls (HC). 
This project will study women only. Anorexia nervosa among males is relatively rare, males with AN have 
many atypical features (Andersen and Holman, 1997). Especially for a study design to be developed as in this 
application, it is important to keep variance, including sex, low. However, males will be included in future 
studies.    
 
Inclusion of Minorities: The racial distribution of study participants with anorexia nervosa depends on 
individuals referred to the two treatment centers where we recruit from (UC San Diego Health Eating Disorders 
Center for Treatment and Research). Healthy controls will be matched to those individuals. The referral area to 
those treatment programs is primarily Southern California, however, the programs also draw patients 
nationwide. Therefore, it is reasonable to estimate subject recruitment based on the California State Census. As 
per the 2010 US Census data (factfinder.census.gov) the racial distribution of the population is as follows: 
White 57.6%, Black or African American 6.2%, American Indian/Alaskan 1.0%, Asian 13.0%, Native 
Hawaiian 0.4%, More than one race 4.9%; Non-Hispanic White 40.1%, Latino 37.6%. Number of subjects to 
be recruited is reflected in the Enrollment Table.   
 
 


 
 
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Minority groups present less often to treatment facilities. This may reduce access to individuals from a minority 
background. However, a special effort will be made for the recruitment of minority populations: 
Study Population. 
 
Eating disorders commonly occur in industrialized nations, but immigrants from nations where the disorders 
are rare assimilate and also may develop eating disorders, presumably because of exposure to thin-body ideals 
(American Psychiatric Association, 2000). There is very limited research on the prevalence of eating disorders 
in minority groups. However, anorexia nervosa was found to be more common in white compared to black 
individuals in one study (Striegel-Moore et al., 2003), and another found eating disturbances compared to 
Caucasian females to be equally common among Hispanic females, more frequent among Native Americans, 
and less frequent among Black and Asian American females (Crago et al., 1996). This highlights the need to 
reach out toward minority groups, in particular, Hispanic and Native American individuals. The nature of the 
study with many questionnaires and the specific neuroimaging tasks prohibit us to have all material and tasks in 
Spanish. However, it is our experience that the largest portion of individuals who might qualify for the study 
will be able to communicate in English. The applicant will approach those groups by providing teaching about 
eating disorders in those communities and provide information on the severity of illness and treatment options.  
Outreach Plan. 
We will make a special effort to match subjects with anorexia nervosa with healthy controls that come from 
similar ethnic background. There are several Universities in the San Diego area including UCSD as well as San 
Diego State University with multicultural student organizations.  
We will carefully assess recruitment resources, incentives, and problem-solving mechanisms, and monitor the 
success closely.  
Communication. 
 
A main obstacle in the recruitment of minority groups is a lack of trust and knowledge (Outreach Notebook, 
NIMH). Thus, we will offer any of the contacted interested organizations to give a presentation regarding the 
study to promote understanding, awareness, and trust. The PI is already giving seminars to parents of patients 
with eating disorders or at local health fair events and will be more than happy to provide findings further and 
teaching for research staff, health care providers, participants, and their families and communities. This will 
increase trust and fruitful long-term collaboration. 
Data Storage and Data Analysis Plan 
All paper data will be stored in locked cabinets in the PI office space at UC San Diego Health Eating Disorders 
Center for Treatment and Research (4510 Executive Dr. Suite 330). All electronic data will be stored on the 
VRD server created for Dr. Frank’s lab by the ACTRI (see section 16 PRIVACY AND CONFIDENTIALITY 
CONSIDERATIONS INCLUDING DATA ACCESS AND MANAGEMENT below for more details).    
We will extract for both tasks mean parameter estimates from 18 predefined anatomical regions of interest 
(ROIs) (http://marsbar.sourceforge.net/, automated anatomical labeling Atlas, AAL (Tzourio-Mazoyer et al., 
2002)) based on previous studies (DeGuzman et al., 2017): dorsal and ventral anterior insula, caudate head, 
gyrus rectus, medial, middle and inferior OFC, ventral striatum (O'Doherty et al., 2004) and nucleus accumbens 
(Breiter et al., 1997). Extracted ROI data will be analyzed using SPSS 24 (IBM statistical software) using 
repeated measures ANCOVA. Extracted regional brain activation parameter estimates will be tested for 
normality with the Shapiro-Wilk test, rank-transformed when non-normally distributed and analyzed using 
repeated measures ANCOVA with covariates as in previous studies to account for confounding factors such as 
comorbidity or medication (DeGuzman et al., 2017). Spearman’s rank will be used for correlation analyses and 
controlled for multiple comparisons using bootstrapping (1000 samples) (Westfall, 2011). We will also conduct 
exploratory whole-brain analyses to test for areas of interest outside of our predefined ROIs and create PE 
response maps, with maps thresholded at voxel level p<0.05, FWE corrected (very stringent), 10 voxel 
minimum cluster contiguity, as well as voxel level p<0.001 and p<0.05 cluster level corrected (exploratory), 


 
 
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Statistical Power. This is a developmental grant application and we cannot be certain whether the study has 
sufficient power. However, previous studies using comparable designs and similar sample sizes showed 
significant within and between group results (Diederen et al., 2017). Studies from our group (Frank et al., 
2018a) indicated that subject groups of 20 per group should provide sufficient power based on for instance 
caudate nucleus PE parameter estimate means of 67.8 (adolescent AN) and 40.2 (adolescent controls), with a 
mean standard deviation of 28, to reach a power of 0.8, p<0.05. Thus, our sample size for the fMRI study 
should be adequate and be able to replicate our previous results (elevated PE) and provide adequate pilot date 
for the new analyses in this application. A main goal of this application to investigated data distribution, 
standard deviation, etc. for future studies. 
 
10. HUMAN SUBJECTS 
 
Total Enrollment: 104 subjects (34 anorexia nervosa and 70 healthy controls) 
Age Range: 18 to 29 years old 
Gender: Female 
Ethnic Background: All races and ethnicities 
Health Status: See below 
 
 
Description of Population to be Enrolled:   
 
Subject population: Subjects will consist of female adults, ages 18 to 29 years old. We plan on completing a 
total of 44 subjects over 2-3 years. We expect to enroll up to an additional 60 subjects who will be disqualified 
during the screening process. Subjects will reflect the racial/ethnic composition of women in San Diego, CA. 
Total number of participants to be enrolled is 104.  
 
Inclusion Criteria:   
 
Healthy Controls 
• Females ages 18-29 years 
• Healthy body weight between 90 and 110 % average body weight since puberty.  
• Regular monthly menstrual cycle 
• Edinburgh Handedness Inventory Revised (EHI-R) LQ* score > +200 
• English is primary language spoken 
 
 
Anorexia Nervosa 
• Females ages 18-29 years 
• Diagnostic criteria. Current diagnosis of AN, including being underweight below 17.5 body mass index 
(BMI, kg/m2), will have a severe fear of weight gain, body image distortion and absence of the 
menstrual cycle over three consecutive months.  
• Edinburgh Handedness Inventory Revised (EHI-R) LQ* score > +200 
• English is primary language spoken 
 
 
Exclusion Criteria:   
 
Healthy Controls 


 
 
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• Current pregnancy or breast feeding within last 3 months 
• Illiterate/Blind individuals 
• First degree relative with current or past eating disorder 
• Current Medications other than BCP or IUD 
• Contraindications to amisulpride or bromocriptine (as determined through medical history in bioscreen 
and PI interview) including: Syncopal migraine; Uncontrolled hypertension; Pheochromocytoma; 
Prolactinoma; Breast cancer; hypersensitivity/allergy to amisulpride or bromocriptine; History of long 
QT syndrome; Family history of sudden death or long QT syndrome; History of seizures or seizure 
disorder 
• Past or present Axis I psychiatric disorder including substance or alcohol use disorder as determined 
through SCID-5 clinical interview   
• Major Medical illness (as determined through medical history in bioscreen and PI interview) such as:  
o Conditions that are life threatening: 
§ cancer 
§ heart disease 
§ stroke 
§ HIV/AIDS 
o Conditions that are life threatening Conditions that cause serious disability without necessarily 
being life threatening:  
§ stroke 
§ closed head or spinal cord injuries 
§ mental retardation 
§ congenital malformations. 
o Conditions that cause significant pain or discomfort that can cause serious interruptions to life 
activities: 
§ severe allergies 
§ migraine 
§ arthritis 
§ sickle cell disease 
o Conditions that require major commitments of time and effort from care-givers for a substantial 
period of time: 
§ mobility disorders 
§ blindness 
§ Alzheimer's disease and other dementias 
§ chronic obstructive pulmonary disease 
§ paraplegia or quadriplegia 
§ Down's syndrome 
§ depression 
o Conditions that may require frequent monitoring: 
§ diabetes 
§ conditions requiring anticoagulation treatment 
§ severe asthma 
§ severe allergies 
§ schizophrenia and other psychotic illnesses. 
o Conditions that predict or are associated with severe consequences: 
§ hypertension (associated with heart disease) 
§ depression (associated with suicide) 
§ diabetes (associated with blindness, kidney failure) 


 
 
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§ alcohol and other substance abuse (associated with intentional and unintentional 
injuries). 
• Recent history of suspected substance abuse or a lifetime history of psychostimulant abuse and/or 
dependence 
• Metal implants or braces (as determined through fMRI screening form) 
 
Anorexia Nervosa 
• Pregnancy or breast feeding within last 3 months 
• Lifetime history of bipolar disorder or psychosis 
• Illiterate/Blind individuals 
• Contraindications to amisulpride or bromocriptine (as determined through medical history in bioscreen 
and PI interview) including: Syncopal migraine; Uncontrolled hypertension; Pheochromocytoma; 
Prolactinoma; Breast cancer; hypersensitivity/allergy to amisulpride or bromocriptine; History of long 
QT syndrome; Family history of sudden death or long QT syndrome; History of seizures or seizure 
disorder 
• Use of an anti-psychotic or other dopamine acting medication including stimulants within the past week 
at time of MRI 
• Recent history of substance abuse or dependence (within the last month) 
• Major Medical illness (as determined through medical history in bioscreen and PI interview) such as:  
o Conditions that are life threatening: 
§ cancer 
§ heart disease 
§ stroke 
§ HIV/AIDS 
o Conditions that are life threatening Conditions that cause serious disability without necessarily 
being life threatening:  
§ stroke 
§ closed head or spinal cord injuries 
§ mental retardation 
§ congenital malformations. 
o Conditions that cause significant pain or discomfort that can cause serious interruptions to life 
activities: 
§ severe allergies 
§ migraine 
§ arthritis 
§ sickle cell disease 
o Conditions that require major commitments of time and effort from care-givers for a substantial 
period of time: 
§ mobility disorders 
§ blindness 
§ Alzheimer's disease and other dementias 
§ chronic obstructive pulmonary disease 
§ paraplegia or quadriplegia 
§ Down's syndrome 
o Conditions that may require frequent monitoring: 
§ diabetes 
§ conditions requiring anticoagulation treatment 
§ severe asthma 


 
 
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§ severe allergies 
§ schizophrenia and other psychotic illnesses. 
o Conditions that predict or are associated with severe consequences: 
§ hypertension (associated with heart disease) 
§ diabetes (associated with blindness, kidney failure) 
§ alcohol and other substance abuse (associated with intentional and unintentional injuries) 
within the last month 
• Metal implants or braces (as determined through fMRI screening form) 
    
 
Rationale for excluding subjects based on gender, primary language spoken, and blind/illiterate individuals:  
 
All subjects will be female. AN among males is relatively rare (less than 10%), males with AN have many 
atypical features (Andersen and Holman, 1997), and they will be subject of a different study. Our study 
involves several assessments and MRI tasks that have not been translated into different languages. We will only 
include individuals whose primary spoken language is English and will also exclude subjects who cannot read 
or see since the MRI tasks have visual stimuli.  
 
11. RECRUITMENT AND PROCEDURES PREPARATORY TO RESEARCH 
 
Selection of study population   
 
Subjects will be recruited from UC San Diego Health Eating Disorders Center for Treatment and Research, as 
well through local advertisements. Subjects will reflect generally the socioeconomic and ethnic distribution of 
California as many patients come from the entire state.  
 
Patient accrual  
 
All subjects will be accrued locally. Individuals with AN ages 18-29 years will be recruited primarily from UC 
San Diego Health Eating Disorders Center for Treatment and Research, which treats per year across residential, 
day hospital, and intensive outpatient program more than 100 adult patients with anorexia nervosa. Willingness 
to participate and study eligibility ranges between 40 and 60%. We will study subjects within 1-2 weeks of 
admission in order to avoid the confounding effects of acute starvation or dehydration. Healthy controls ages 
18-29 years will be recruited through local advertisements. Healthy controls will be studied during the first ten 
days of the menstrual cycle to keep hormonal variation low.  
 
 
AN Subjects from UC San Diego Health Eating Disorders Center for Treatment and Research: Dr. Frank is an 
attending physician at the UC San Diego Health Eating Disorders Center for Treatment and Research program.  
Any eligible patients who are admitted into these programs will be screened and approached by the PI and/or 
research staff regarding their participation in the study.  Prior to approaching the patient, Dr. Frank and/or his 
staff will obtain permission from the patient’s individual therapist prior to making contact with the patient to 
describe the research opportunity. The research staff will complete the initial screening to determine eligibility. 
After determining initial eligibility, the PI or research staff will obtain consent from these individuals in person.  
All diagnostic assessments, questionnaires, and procedures will be conducted in the PI’s/Research staff’s 
private office (at the UC San Diego Health Eating Disorders Center for Treatment and Research), Altman  
Clinical Research Institute, or at the Sharp and Children’s MRI Center (for the scanning procedures).   
 


 
 
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HC Subjects from local areas: Advertisements will be posted online and throughout the community to recruit 
for healthy control adults for this study.  All interested individuals will contact the research staff.  If interested 
in moving forward with the study procedures, the research staff will obtain some initial screening information 
over the phone to determine initial eligibility.  This form will ask about current height, weight, age, gender, 
handedness, medication use, referral source and metal implanted in body.  If the individuals meet initial criteria, 
the consent will be described over the phone, and a consent packet and questionnaire packet will be mailed to 
the individual with a stamped return envelope.  The questionnaire and consent packet will consist of the 
following: EDI-3; SPSRQ; BDI-II; TCI; EDE-Q; STFCQ; TEPS; EEI; PBI; BCIS, SAI-ED, IUS, BIS/BAS; 
ACEs; fMRI screening form; Race and Ethnicity Form; Contact Information Form, ICF and HIPAA forms.  
  
Once the coordinator receives the completed consents and questionnaires, the Initial Screening Form will be 
destroyed.  If no packet is received within 3 months of the Initial Screening Form (Pre-screening-
Form_072219.pdf and InitialScreeningContact_072219.docx) the Screening Contact Form will be 
destroyed. The research staff will score the questionnaires, as those assessments are used to further screen 
individuals for the study.  The individual will then complete a Biological Screening Form questionnaire that 
goes over more details about eating and psychiatric history to rule out or confirm any eating disorder 
symptomatology.  If at that point the subject still meets study criteria, he/she will be invited in for the in-person 
interview with the PI at UC San Diego Health Eating Disorders Center for Treatment and Research .  At this 
interview, the consents will be reviewed with the subject in person to ensure they are aware of all of the study 
risks and procedures as well as for the PI to confirm they are eligible for the study. The subject will be given 
the opportunity to ask any questions about the study procedures and will be given a signed copy of the consent 
form. The final step before the MRIs is for the individual to complete the diagnostic assessment, SCID, which 
will be completed over the phone or in person (preference of the individual) by the PI or other doctoral level 
clinician.   
 
If subjects pass this section and are still interested in the study, they will be scheduled for a brain scan at the 
Sharp and Children’s MRI Center. Upon completion of the imaging study, subjects will be paid for their effort 
and time. Subjects will be given the opportunity to sign a consent to be re-contacted for future studies. 
Subjects’ well-being will be monitored by the study personnel throughout the study. 
 
Request for Waiver of Consent 
 
Initial Screening and Identification of Potential Subjects 
 
We are requesting a waiver of consent for the screening process.  
 
In order to recruit eating disorder participants who are potentially eligible for the current study (e.g., adult 
women with AN), a waiver of consent is requested. Specifically, this will allow for an identification of adult 
female patients at the UC San Diego Health Eating Disorders Center for Treatment and Research program who 
are seeking treatment for AN, and thus meet these primary inclusion criteria for the research.  
 
We are requesting a waiver of written documentation of consent for the Initial Screening Form (Pre-screening-
Form_072219.pdf). This initial screening asks verbal permission to obtain preliminary information: age, 
weight, use of medications, handedness, metal in body in a “yes/no” response format, and is recorded on a 
separate sheet from identifying information.  Our procedure is to establish if prospective study participants 
meet minimal criteria as described before proceeding to explain the protocol and obtain written consent.  If 
preliminary requirements are met, this information is destroyed.  
 


 
 
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Healthy Control Subjects: After the Initial Screening Form is completed, the study procedures will be explained 
to the subject in detail and questions about the study will be answered. If the subject would like to continue 
with the study, contact information including: Name, Address, Phone Number, and Email Address will be 
obtained (InitialScreeningContact_072219.docx).  A consent and questionnaire packet will be mailed to the 
subject. Healthy Control subjects will complete the questionnaire packet and return along with the signed 
consent form via mail. This questionnaire packet will be used in the screening process and will help determine 
whether a subject is eligible for the study. Formal in-person consent will not be completed until the diagnostic 
in-person interview and so we are requesting an alteration of written consent documentation for the phone 
screenings as well as the questionnaire packets since consent will not be obtained in person prior to these 
screenings. The initial packet contains the following documents:  Initial Study Packet Letter, Informed Consent 
Form (2 copies), Race & Ethnicity Form, Questionnaire Packet, Contact Information Form, fMRI Screening 
form.  
 
Anorexia Nervosa Subjects: After the initial screening form is completed, the research staff will review the ICF 
with the subject and complete the consent process listed below in Item 11, Informed Consent.  
 
1. The research is minimal risk. 
 
The identification AN patients in the UC San Diego Health Eating Disorders Center for Treatment and 
Research Program would be of minimal risk to potential participants, as the information would be accessible 
only to members of the study staff directly involved with recruitment.  
 
The Initial Screening Form is only completed after the subject gives verbal consent to ask the screening 
questions. The Initial Screening Form that contains eligibility information such as age and medications is 
destroyed after determining eligibility. The Screening Contact Form that is completed for eligible subjects will 
be kept in a locked cabinet and access will be restricted to Dr. Frank and his research staff.  
 
 
2. The waiver will not adversely affect the rights and welfare of the subjects.  
 
The identification AN patients in the UC San Diego Health Eating Disorders Center for Treatment would not 
adversely affect the rights and welfare of the subjects. As there are several ongoing studies at these programs at 
any given time, participants who are approached to determine their potential interest in the study would not be 
unduly singled out. Further, the waiver would not adversely affect the rights and welfare of the participants, as 
their decision whether or not to participate in the study if approached would have no effect on the care that they 
are receiving at the program. Importantly, the research staff will emphasize to the patients that participation in 
the research in no way influences eligibility to receive treatment at UCSD or elsewhere, and that participation is 
entirely voluntary. Participation of patients will be scheduled to reduce interference with treatment 
programming, and during recruitment, it will be emphasized that payment only compensates participants for 
their research-specific time and parking. It will also be emphasized that participants may withdraw their 
consent and decide not to participate at any time with no impact on their treatment at UCSD or elsewhere.  
 
Prior to completing the Initial Screening Form, subjects give their verbal permission to complete the form. 
After the form is completed and eligibility is determined the consent forms are explained to the subject and the 
subject is asked if she has any questions and would like to continue with the study process. After the screening, 
only the Screening Contact Form is kept and it is stored in a secure location with minimal risk of a 
confidentiality breach.  
 
3. The research could not practicably be carried out without the waiver.  


 
 
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The identification AN patients in the UC San Diego Health Eating Disorders Center for Treatment and 
Research Program could not practicably be carried out without the waiver. AN is a disorder with a relatively 
low prevalence in the US (0.9% of women), and as such, it would be impractical to obtain the necessary sample 
through community-based recruitment. The waiver of consent is requested because the recruitment of a sample 
of AN women could not be practically carried out at the eating disorder programs without the identification of 
those adult patients who are diagnosed with AN. 
 
The Initial Screening Form is needed to determine initial eligibility criteria for the study.  Our study has very 
strict eligibility criteria for healthy controls and therefore it is more efficient to screen interested individuals 
prior to having them complete all of the consents/forms/questionnaires.  Since many will live outside the 
immediate UCSD campus area, potential research subjects would probably be unwilling to participating if they 
were required to come to UCSD to sign a written consent and undergo the initial screening.  Also, since many 
healthy control subjects are excluded before completing the entire initial screening (in our previous experience 
about 50 percent are excluded prior to the in-person interview), requiring a trip to UCSD for a preliminary 
screening would be very time and cost intensive and therefore delay the completion of the study.  Therefore, 
these subjects approaching us about participating in research will undergo a brief interview or telephone 
screening conducted by our research staff.  
 
Many of AN subjects will be ineligible due to handedness, age or MRI contraindications such as metal in the 
body and so having them complete the initial screening form before the full consent process will help minimize 
the time these patients have to spend away from program for research activities.  
 
4. The subjects will be provided with additional pertinent information after participation. 
 
There will be no additional information provided to subjects after participation in the screening procedures. 
Subjects who are not eligible or decline to participate in the study after the initial screening will not have 
contact information or PHI stored and there will be no method of contacting them regarding any pertinent 
information.  
 
 
Request for Partial Waiver of  HIPAA Authorization 
 
Initial Screening  
 
 
We are requesting a partial waiver of HIPAA Authorization for the screening process.  
 
Healthy Controls: Advertisements will be posted online and throughout the community to recruit for healthy 
control adults for this study.  All interested individuals will contact the research staff.  If interested in moving 
forward with the study procedures, the research coordinator will obtain some initial screening information over 
the phone to determine initial eligibility.  This form will ask about current height, weight, binge behaviors, age, 
gender, handedness, medication use, referral source and metal implanted in body.  If the individuals meet initial 
criteria, the consent will be described over the phone and questions will be answered. After the subject confirms 
they wish to continue with the study a consent packet and questionnaire packet will be mailed to the individual 
with a stamped return envelope.   
 
The questionnaire packet will consist of the following: EDI-3; SPSRQ; BDI-II; TCI; EDE-Q; STFCQ; TEPS; 
EEI; PBI; BCIS, SAI-ED, IUS, BIS/BAS; ACEs; fMRI Screening Form, Race and Ethnicity Form. These 


 
 
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forms will not contain an area for the subject to enter PHI. The consent packet will include 2 copies of the 
consent form and the Contact Form and will be included in this mailed forms. The mailed forms will not 
contain both PHI and project ID. 
 
The individual will then complete a Biological Screening Form questionnaire over the phone that goes over 
more details about eating and psychiatric history to rule out or confirm any eating disorder symptomatology.  If 
at that point the subject still meets study criteria, she will be invited in for the in-person interview with the PI at 
UC San Diego Health Eating Disorders Center for Treatment and Research.   
 
At this interview, the consents will be reviewed with the subject in person to ensure they are aware of all of the 
study risks and procedures as well as for the PI to confirm they are eligible for the study. The subject will be 
given the opportunity to ask any questions about the study procedures and after a complete review of the 
consent forms, subjects will complete a new consent form (the consent form completed via mail as well as this 
newly completed consent form will be kept in the subject’s folder) and the subject will be given a signed copy 
of the consent form.  
 
If the individual does not meet preliminary criteria based on the answers on the Initial Screening Form, the 
information on the form will be destroyed.  If the subject meets preliminary criteria and a consent/questionnaire 
packet is mailed to the subject, we will destroy the Screening Contact Form once we receive the completed 
submission packet back with completed consent forms and questionnaires.  The Screening Contact Forms of the 
individuals who have not submitted consents will remain in a locked file cabinet in the locked office of the 
research coordinator.  If no packet is received within 3 months of the Initial Screening Form, the Screening 
Contact Form will be destroyed.  The Initial Screening Form is needed to determine initial eligibility criteria for 
the study.  Our study has very strict eligibility criteria and therefore it is more efficient to screen interested 
individuals prior to having them complete all of the consents/forms/questionnaires.  The PHI is necessary to 
collect because we send questionnaires and consent forms to these individuals.  We mail the consents prior to 
having the individual come into the UC San Diego Health Eating Disorders Center for Treatment and Research 
in person because of the lengthy screening process and would like to minimize the amount of travel time 
required for each individual.   
 
Anorexia Nervosa: Dr. Frank is an attending physician at UC San Diego Health Eating Disorders Center for 
Treatment and Research programs.  Any eligible patients who are admitted into these programs will be 
screened and approached by the PI and/or research staff regarding their participation in the study.  Prior to 
approaching the patient, Dr. Frank and/or his staff will obtain permission from the patient’s individual therapist 
prior to making contact with the patient to describe the research opportunity. The Research Staff will complete 
the Initial Screening Form to determine eligibility. After determining initial eligibility, the PI or research staff 
will obtain consent from these individuals in person.  In order to recruit participants who are potentially eligible 
for the current study (e.g., adult women with AN), a partial waiver of HIPAA authorization is requested. 
Specifically, this will allow for an identification of adult female patients at the UC San Diego Health Eating 
Disorders Center for Treatment and Research program who are seeking treatment for AN, and thus meet these 
primary inclusion criteria for the research.  
 
5. Plan to a) protect identifiers from improper use and disclosure and b) destroy identifiers at the earliest 
opportunity. 
 
All subjects will be assigned a “Recruitment Tracking #” prior to the Initial Screening. This number will be 
used in the Recruitment Log to track when a subject was approached, determined ineligible, or declined to 
participate (for AN subjects) and track when a research packet was sent and return and will associate the 
Screening Contact Form with the correct subject (for Healthy Control subjects). This Recruitment Tracking # 


 
 
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will be placed on the questionnaire packet that is mailed to the healthy control subjects. Only the lab manager 
and PI will have access to the key of recruitment tracking # and associated subject identity. 
 
Healthy Control Subjects: After receiving the completed questionnaire and consent packet back in the mail, Dr. 
Frank’s research staff will create a subject folder and will assign a Subject #. Only Dr. Frank and his lab 
manager will have the key to the Subject #s and Recruitment Tracking #s and associated subject identities.  
 
Anorexia Nervosa Subjects: After enrolling in the study, Dr. Frank’s research staff will create a subject folder 
and will assign a Subject #s. Only Dr. Frank and his lab manager will have the key to the Subject #s and 
Recruitment Tracking #s and associated subject identities.  
 
The Initial Screening Form will be destroyed after determining eligibility. The Screening Contact Form 
(healthy controls only) will be kept until the questionnaire/consent packet is returned for up to 3 months. After 
the completed research packet and signed ICF are returned, the screening contact form will be destroyed and a 
subject folder will be created for the enrolled subject. If no packet is returned within 3 months, the screening 
contact form will be destroyed.  
 
6. Indicate why these procedures could not a) practicably be done without the waiver, and b) be done without 
access to, use, or disclosure of PHI. 
AN is a disorder with a relatively low prevalence in the US (0.9% of women), and it would be impractical to 
obtain the necessary sample through community-based recruitment. The recruitment of a sample of AN women 
could not be practically carried out at the UC San Diego Health Eating Disorders Center for Treatment and 
Research without the identification of those adult patients who are diagnosed with AN. As noted above, the 
privacy risk will be minimal, as the limited PHI (name, age, primary ED diagnosis) will be accessible only to 
members of the study staff directly involved in recruitment.  
 
The Screening Contact Form (healthy controls) is needed in order to send the research packet.  
For Healthy Controls, the PHI is necessary to collect because we send questionnaires and consent forms to 
these individuals.  We mail the consents prior to having the individual come into the UC San Diego Health 
Eating Disorders Center for Treatment and Research in person because of the lengthy screening process and 
would like to minimize the amount of travel time required for each individual.   
 
7. Indicate why the privacy risk to individuals whose PHI will be used or disclosed is minimal and reasonable 
in relation to the anticipated benefit, if any, to the individuals.  
The identification of the adult patients who are diagnosed with AN privacy risk will be minimal, as the limited 
PHI (name, age, primary ED diagnosis) will be accessible only to members of the study staff directly involved 
in recruitment. Although no direct benefits are expected for participants in this research, they could potentially 
benefit from the psychological interviews that include a focused examination of psychiatric symptoms and 
history, and they may also gain satisfaction from contributing to increased knowledge on neurobehavioral 
mechanisms of AN. Participants who are enrolled into the study will be asked to sign a HIPAA authorization 
form along with the informed consent document, while the PHI for individuals who either choose not to 
participate or who are found to be ineligible will be immediately and permanently deleted. Access to 


 
 
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information including age, sex, and ED diagnosis is requested for this waiver, as these details will allow for the 
targeted recruitment approach that is necessary to practically and feasibly carry out this research. 
 
The Screening Contact Form (healthy controls only) is kept in a locked cabinet that only Dr. Frank and his 
research staff have access to.  
The identification key to the Recruitment Tracking # and Subject # will be stored in a password-protected 
databases on secured computers that are accessible only to the PI and lab manager.  
 
 
8. Indicate what PHI will be used and who will access, use or disclose the PHI.  
The identification of the adult patients who are diagnosed with AN is limited to the following PHI: Name, Age 
Primary ED diagnosis and history. This PHI will only be used to identify which patients might be eligible. Only 
research staff directly involved in this study will have access to this information.  
The Screening Contact Form (healthy controls) will contain: Name, Address, Email, and Phone Number. This 
information will be used to mail the consent/questionnaire packet to the potential subject. Mailed packets will 
not contain materials that have both PHI and project ID.  
The Recruitment Tracking # and Subject # Identification Keys will contain the name and associated Tracking 
and Subject #s. Only the PI and Lab Manager will have access to this PHI.  
 
12. INFORMED CONSENT 
 
Consent Procedures  
 
AN subjects from UC San Diego Health Eating Disorders Center for Treatment and Research 
 
As a provider of the UC San Diego Health Eating Disorders Center for Treatment and Research, Dr. Frank has 
a clinical relationship with the patients in treatment at these programs. He and his staff will screen new 
admissions to determine potential subjects. Prior to approaching the patient, Dr. Frank and/or his staff will 
obtain permission from the patient’s individual therapist prior to making contact with the patient to describe the 
research opportunity. 
 
Dr. Frank’s research staff will approach potential subjects and get their verbal consent to complete the initial 
screening (Pre-ScreeningForm_072219.pdf). Prior to approaching any potential subject, the research staff will 
contact the patient’s primary therapist After completing the initial screening form, the research staff will 
destroy the pre-screening form. If the subject is eligible, the research staff will review the consent forms and 
complete the consent visit as outlined below:  
 
1. The person obtaining consent (i.e. the research assistant or PI) will be trained to answer questions and 
explain the study and document the consent process.  Any person involved in the consent procedures will have 
completed the UCSD HRPP educational requirements.   
 


 
 
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2. The setting in which the consent will be obtained will be in a clinic or research setting (UC San Diego Health 
Eating Disorders Center for Treatment and Research, in a quiet room with no distractions.  The subject will 
have unlimited time to read and ask questions about the study and the consent process.  Patients in this research 
study will be informed about the purpose and the duration of the current study.  Informed consent will be 
obtained once the subject has been informed and wants to participate in the investigation using the attached 
consent form.  The PI or research assistant will go through the consent form with the subject and will obtain 
written consent.   
 
3. The subject's comprehension and autonomy will be assessed by asking the subjects to explain in their own 
words the study procedures in order to assure the understanding and ability to consent.   
 
Consent and willingness to participate will be confirmed by staff in person prior to conducting any other study 
procedures.  The PI who has extensive experience with screening subjects for similar studies will perform 
initial screening and assessments. However, HRPP certified staff will also be trained to perform screening and 
subject enrollment. Subjects will be explained the study, will have time to review any consent papers and will 
sign when in the office and after further discussion of the study participation. 
 
Subject’s comprehensive autonomy is assessed by having subjects report back on how they understand the 
study in their own words and the PI /study personnel will judge if subjects understood correctly. After all 
questions about the study are answered the consent form will be signed by the subject and a copy of the consent 
will be provided to subjects. The consent will be kept in the participating subjects’ files. 
 
In addition to the general consent, participants will also be given the option on the consent forms to opt-in to 
allow their data to be shared with other research teams at the UC San Diego Health Eating Disorders Center for 
Treatment and Research who are studying eating disorders.  
 
 
A copy of the consent will be provided for the subject.  
 
The consent process will be documented in the subject's summary checklist.   
 
Healthy Controls from the Community 
 
Potential subjects will voluntarily contact us about participating in this research either by phone or in writing.  
The study will be advertised on posted flyers and research web pages that will include our research office 
contact information.   
 
Since many will live outside the immediate UCSD campus area, potential research subjects would probably be 
unwilling to participating if they were required to come to UCSD to sign a written consent and undergo the 
initial screening.  Also, since many subjects are excluded before completing the entire initial screening (in our 
previous experience about 50 percent are excluded prior to the in-person interview), requiring a trip to UCSD 
for a preliminary screening would be very time and cost intensive and therefore delay the completion of the 
study.  Therefore, these subjects approaching us about participating in research will undergo a brief interview 
or telephone screening conducted by our research staff.  
 
We are requesting a waiver to document consent for the initial screening process only.  A brief, verbal 
screening tool will be used (Pre-screening-Form_072219.PDF and InitialScreeningContact_072219.docx) 
 


 
 
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This Initial Screening Form asks the individual for verbal permission to obtain preliminary information: age, 
height, weight, gender, binge eating behavior, handedness, implanted metal, use of medications, and referral 
source as well as contact information of the individual.  Our procedure is to establish if prospective study 
participants meet minimal criteria as described before proceeding to explain the protocol and obtain written 
consent.   
 
After the research assistant determines the subject meets the initial criteria, the study procedures will be 
described over the phone to the subject, questions will be answered, and if the subject agrees a questionnaire 
packet and consent form will be mailed to the subject.  
 
We will add to the information sheet, which has name and address, to document that verbal permission was 
obtained to obtain name/address. The questions we are asking during this initial screening are the same as 
would be asked if the subject was being set up for a clinical appointment.  The only information retained will be 
name and address, email and phone number if the subject is willing to do so 
(InitialScreeningContact_072219.docx).  
 
We are requesting a waiver of written consent and waiver of HIPAA authorization for the pre-screening 
process. As stated above, the research staff will complete a phone screening to determine initial eligibility 
criteria (Pre-screening-Form_072219.pdf). Once the subject is determined eligible or ineligible this screening 
form will be destroyed. After obtaining verbal consent from the subject to continue with the study, the research 
staff will obtain contact information (InitialScreeningContact_072219.docx) and will send an initial packet to 
them via mail that contains the following: Initial Study Packet Letter, Informed Consent Form (2 copies), Race 
& Ethnicity Form, Questionnaire Packet, Contact Information Form, fMRI Screening form.  
 
If a subject passes the screening processes (Initial Screening Form, Questionnaire Packet in acceptable range, 
Phone Bioscreen), the subject will be invited in for the diagnostic assessment and in person interview with the 
PI. At this visit, the consent form will be reviewed with the subject, questions will be answered, and 
comprehension of study procedures will be assessed. If the subject agrees to continue, she will complete a new 
consent form that will be stored in the subject folder along with the consent form completed via mail that 
accompanied the questionnaire packet. The PI who has extensive experience with screening subjects for similar 
studies will perform initial screening and assessments. However, HRPP certified staff will also be trained to 
perform screening and subject enrollment. Subjects will be explained the study, will have time to review any 
consent papers and will sign when in the office and after further discussion of the study participation. 
 
Subject’s comprehensive autonomy is assessed by having subjects report back on how they understand the 
study in their own words and the PI /study personnel will judge if subjects understood correctly. After all 
questions about the study are answered the consent form will be signed by the subject and a copy of the consent 
will be provided to subjects. The consent will be kept in the participating subjects’ files. 
 
The request for waiver of documented consent for the initial screening portion meets the following criteria from 
45 CFR 46.117(c):  
ii. That the research presents no more than minimal risk of harm to subjects and involves no procedures for 
which written consent is normally required outside of the research context.  
 
For the AN subjects, the initial verbal screening to determine eligibility will be destroyed right after completing 
the screening.  
 
For the HC subjects, the initial verbal screening (Pre-screening-Form_072219.pdf) to determine eligibility 
will be destroyed right after completing the screening. If eligible and subject agrees, they will provide contact 


 
 
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information including name, address, phone, email (InitialScreeningContact_072219.docx) where we will 
send the research packet to them. This initial screening contact information form will be kept in a locked 
cabinet accessible by only Dr. Frank and his research staff.  
 
Data Sharing and Concurrent Enrollment in Protocols 
Some enrolled subjects may be enrolled in another NIMH funded protocol conducted by Dr. Frank’s lab. If the 
subject signs up for multiple, there will overlap in questionnaires and diagnostic interviews. In order to minimize 
the amount of time the subject has to spend doing the study procedures and also to reduce redundancy in study 
procedures, subject’s data will be shared between studies if they are enrolled in both protocols.  
Authorization procedures 
An authorization will be obtained at the time of consent procedures by the PI or trained study personnel. 
A signed and dated copy of the authorization form (included in the combined consent/HIPAA authorization form) 
will be provided to the subject. 
The data acquired will be stored in a locked file cabinet in a locked UCSD research office. A completed 
authorization form with study specific information for HRPP review will be retained in the subjects’ files. 
The authorization portion of the consent forms include UC San Diego Health Eating Disorders Center for 
Treatment and Research as an entity to receive protected health information for only patients enrolled in their 
program.  This information includes scheduling of MRI scans and study procedures so that it does not conflict 
with program time as well as any adverse reactions or events that occur during the testing procedures that may 
impact their treatment in program. 
After signing a written consent/assent, all subjects will complete written self-assessments, as well as structured 
interviews with the research assistant or PI with information stored on a computer. Data from the in-person 
interview will be recorded in writing and stored with the subject's research chart. The Edinburgh Handedness 
Inventory will assess the dominant hand for analysis of handedness and recorded in the subject's research chart.   
After the subject has completed all study procedures and their behavioral data has been entered into our electronic 
database, Dr. Frank’s research staff will create a Certified Electronic Copy of the subject’s paper documents 
which include the signed ICF, questionnaires, contact information, scan assessments, and diagnostic interview 
and the paper documents will be shredded. This Certified Electronic Copy will be kept on a secure UCSD server 
that is password protected and encrypted. Only Dr. Frank and his research staff will have access to these 
documents.  
Study Assessments: All subjects will be administered the structured clinical interview for DSM-5 diagnoses 
(SCID) by a PhD level Psychologist or the PI. All participants will complete the Eating Disorder Inventory-3 
(Garner 2004, Cumella 2006), revised Sensitivity to Punishment and Sensitivity to Reward Questionnaire 
(SPSRQ) (Torrubia, Avila et al. 2001), Beck Depression Inventory (BDI-II) (Beck, Steer et al. 1996), 
Temperament and Character Inventory (Cloninger, Przybeck et al. 1994), Eating Disorders Examination 
Questionnaire (EDE-Q) (Fairburn 2005), State and Trait Food Cravings Questionnaire (STFCQ, craving self-
report) (Cepeda-Benito, Gleaves et al. 2000, Moreno, Rodriguez et al. 2008, Van den Eynde, Claudino et al. 
2010, Van den Eynde, Koskina et al. 2012), Temporal Experience of Pleasure Scale (TEPS, food and non-food 


 
 
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anticipatory and consummatory experiences of pleasure) (Gard, Germans-Gard et al. 2006), Eating Expectancy 
Inventory (EEI, cognitive expectations for eating) (Hohlstein, Smith et al. 1998), Parental Bonding Instrument 
(PBI, parental bonding may be a moderator of brain dopamine release) (Parker 1989, Pruessner, Champagne et 
al. 2004), Schedule for the Assessment of Insight for eating disorders (SAI-ED) (Konstantakopoulos et al., 
2011), Adverse Childhood Experiences Questionnaire (ACEs, Feelitti et al, 1998), Behavioral Inhibition 
Scale/Behavioral Activation Scale (BIS/BAS, Carver & White, 1994), Intolerance of Uncertainty Scale (IUS, 
Freeston et al, 1994).  
 
13. ALTERNATIVES TO STUDY PARTICIPATION 
There is no direct benefit to the participant. The alternative to study participation is to not participate in the 
study.  
 
14. POTENTIAL RISKS 
 
Potential Risks 
 
It is our experience that individuals with eating disorders including AN are willing to cooperate with such 
studies. Over the past 12 years we have recruited and studied close to 400 subjects and had no incident that 
would indicate any risk. The studies were not psychologically traumatic to adolescents or adults in the past. We 
do not feel that these studies pose any significant psychological risk for patients or control study subjects. Many 
measures are in place to assess and avoid risks.  
 
Computer Testing/Interviewing.  The main risks associated with these procedures are fatigue and irritability 
with the testing procedure. The investigator and research associates are trained to frequently ask the subjects 
about their willingness and ability to continue with testing. If a subject expresses concerns about continuing 
with testing, the investigator has instructed the research associate to stop testing, offer a break, or, if the subject 
is not willing to continue, to terminate the testing session. Overall, however, previous studies have not resulted 
in any significant discomfort or anxiety expressed by the participating subjects.  
 
Social Risk. There is no social risk associated with the participation in this study, all results will be kept strictly 
confidential and will not be used to influence any clinical decision making. There are no legal risks associated 
with these paradigms.  There are no other known risks associated with participation in this study. AN patients 
will continue to receive their current treatment, which is not being suspended or modified in any way for 
research purposes. 
 
fMRI Brain Imaging. There are two major sources of risk. First, there could be risk from the magnetic field in 
the MR scanner, second the subject may experience discomfort being in the confined environment of the 
scanner (claustrophobia) with exposure to noise, and third, the subject may experience discomfort carrying 
out the task. The Sharp & Children’s MRI Center is run by full time trained technicians who have extensive 
experience and training to conduct safely the here proposed studies. In addition all research personnel involved 
in this study is/will be trained in MR safety by the imaging center staff. 
Exposure to a high magnetic field. The only known hazard associated with exposure to a static high magnetic 
field is that the magnet exerts a strong force on ferromagnetic objects. For this reason, ferromagnetic objects are 
excluded from the vicinity of the magnet so that they will not become projectiles. Conventional MRI uses 1.5 
Tesla (T) magnets. At our Center for Functional MRI, the research systems for human use have field strengths 
of 3T. Imaging at these field strengths is not considered a significant risk according to FDA guidelines. The 
scanning sequences applied are within the FDA guidelines for human MR scanning. 


 
 
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In addition, every subject undergoes two extensive safety screenings to determine whether he/she has any 
implanted materials or braces and dental retainers that may pose a risk. This screening will be done once the 
subject is consented, and another time on each imaging study day. If there is any doubt about the nature of any 
implanted material, or any other indication of contraindication of MR scanning, the subject will not be scanned.  
Every female subject will have a urine pregnancy test that is reviewed prior to scanning and if there is 
indication of pregnancy the subject will be excluded. 
Heating from radiofrequency (RF) pulses. The RF pulses that are used for creating the MR signal deposit some 
energy in the body in the form of heat, but no ionizing radiation is used with MRI. For the same pulse 
sequence, the RF power deposited is higher at higher magnetic field strengths. However, the pulse sequences 
we will use at 3T have relatively low power depositions. In the future, pulse sequences with higher RF power 
depositions may be developed, but we will ensure that the power deposited is always below the FDA 
guidelines. 
 
Peripheral nerve stimulation from rapidly switched magnetic fields (dB/dt). Magnetic field gradients are 
switched on and off during imaging to encode the spatial distribution of the MR signal. Gradient switching rate 
depends on the gradient coil used, but does not depend on field strength. For this reason, the gradient switching 
rates will be similar to those for the 1.5 T scanners we have used in the past, and these rates will not exceed 
FDA recommendations. The FDA guideline states that a significant risk is involved only when “dB/dt rates of 
change sufficient to produce severe discomfort or painful stimulation” is used. All of the fMRI studies 
performed in the past on our 3T system are well below this threshold.  
 
 
Confined space and acoustic noise. The small space in the MRI scanner can cause discomfort and 
feelings of being trapped. This has occurred occasionally in our studies (about 2-3% of studies). Acoustic noise 
is an unwanted side effect of MR imaging. As currents are pulsed through the gradient coils within the 
magnetic field, the system acts like a loudspeaker, making a repetitive tapping sound. At the higher field 
strengths (3T), the acoustic noise is increased. In all of our studies, subjects will wear ear plugs to reduce the 
noise to a comfortable, safe level. Additionally, head phones will be placed over the ears. The FDA guideline 
for a significant risk due to acoustic noise is “peak acoustic noise over 140 dB”, and we will ensure that the 
acoustic levels remain well below this value. 
 
 
Discomfort during the task. It is possible that subjects experience discomfort from the manifold 
placement or taste stimulus application. We have not received such complaints in our previous studies but we 
are very aware of such a possibility and confirm with subjects when we communicate with them during the 
experiment that the manifold placement is pleasant, not irritating and that subjects are comfortable. 
 
Potential Risk of Loss of Confidentiality. Since this study includes medical and psychological assessments as 
well as height, weight and urine pregnancy test assessment, there is the potential that this information may not 
be kept confidential (for instance by theft of study material). The investigator team will make every effort to 
keep all information confidential. All study material will be stored in locked cabinets in the UCSD sponsored 
facilities. Furthermore, a unique study number will be used for each person in data sets and spreadsheets that do 
not readily identify a name. The identifying name information containing material will be locked. The 
information shared over the EMA server will not include identifying information. This system is secured as 
described above and only the PI and his staff will know the identity of each subject registered in the system.  
 
Medical or Psychiatric Emergencies. It is possible that during the assessment procedures or any other time 
during the study any study personnel becomes aware of medically or psychiatrically concerning knowledge, 
including suicidality or homicidality, or child abuse or neglect. Our consent forms include that action will be 
taken and that we may have to contact the authorities. We have a specific procedure in place that will ensure 
subjects’ safety and well-being.  
 


 
 
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Challenge Drug Application: Two dopamine challenge drugs will be applied, amisulpride and bromocriptine. 
Each one of them will be applied only once.  Bromocriptine is a dopamine D2 receptor agonist for the treatment 
of Parkinson's Disease and Type 2 Diabetes. The medication's potential common side effects for ongoing use as 
per the manufacturer include nausea, headache, stomach upset, dizziness, drowsiness, feeling faint, fainting, 
suddenly falling asleep. Serious side effects can include heart attack, stroke, pulmonary fibrosis. Individuals 
whoever took the medication before will be excluded, and the one-time application should at most be associated 
with nausea, headache or dizziness (Diederen et al., 2017). Amisulpride is a selective dopamine D2 receptor 
antagonist used frequently in Europe and other countries for psychotic disorders. Potential side effects during 
ongoing use include fever, excessive sweating, change in heart rate, chest pain, swelling, pain, and redness in 
the legs, increased frequency of infections, skin allergy, seizures, restless legs, twitches in the tongue and face, 
trembling, excessive salivation, constipation, decreased libido, weight gain, amenorrhea, gynecomastia, 
agitation, anxiety, tardive dyskinesia and neuroleptic malignant syndrome. Similarly to bromocriptine, we will 
only include drug naïve individuals and the one-time application has been well tolerated in previous studies and 
we do not expect problems other than maybe nausea (Rosenzweig et al., 2002). 
 
Blood Draw. The main risk with the blood draw is some bruising when the needle goes into the vein and 
bruising at the needle site a day or two after the blood draw.  
 
Electrocardiogram. The main risk is skin rash where electrodes are placed.  
 
 
15. RISK MANAGEMENT PROCEDURES AND ADEQUACY OF RESOURCES 
 
Adequacy of Protection against Risks  
 
Recruitment and Informed Consent.  The Research Assistant will do a brief UCSD Institutional Review Board 
approved screening for age, height and weight over the phone for controls and for AN subjects in their 
respective treatment program together with the PI. All study participants are repeatedly informed that they can 
leave the study at any time and that participation or study decline will have no effect on treatment. 
 
Consent Procedures: Consenting procedures will be HIPPA compliant. The objectives, procedures, and a clear 
statement explaining risks and benefits of the study (as described in the consent form) will be presented to each 
potential subject prior to her/his entry into the protocol. After the study has been explained to the study 
subjects, questions will be asked and elicited in order to ascertain that the subjects comprehend the procedure to 
which they are being asked to give consent to. 
 
Computers.  The computers and the interfacing devices will be checked regularly for proper and safe operation. 
Our computers are also embedded in the UCSD computing network and this ensures strict safety rules and data 
protection by fire walls. 
 
Assessments and Tasks. AN and HC subjects will be carefully screened and subsequently informed about the 
fact that the principal investigator will be available at all times during the experiment. Subjects are informed 
that they may end test sessions at any time and that participation in this research is voluntary. Examiners will be 
clinically trained to be sensitive to signs of stress, anxiety, or fatigue so that testing will be immediately 
terminated should any subject experience signs of discomfort. 
 
Social Risk and Loss of Confidentiality. All staff that participates in this study is HIPAA and conduct of 
research trained according to the UCSD guidelines. A number system will be used for identification of subjects, 


 
 
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and the key that links the number to the subject will be kept in a password-protected Excel file, which will be 
stored on an encrypted laptop that is locked in a cabinet, so to not expose the file to potential attacks to 
networked computers. 
 
 
Brain Imaging. In order to minimize the risk of fear of closed spaces while in the MR scanner, patients will be 
extensively interviewed and informed about the nature of the study.   
During scanning the subject holds an emergency button in her hand that he/she can push and get help at any 
time during the experiment. If at any point during the scanning the subject expresses increasing discomfort, the 
PI, Research Assistant or Sharp and Children’s MRI Center staff will immediately intervene and terminate the 
scanning procedure.   
Exposure to high magnetic fields: All subjects will be screened twice before they will be allowed to enter the 
MRI facilities. Any non-removable magnetic material will automatically exclude subjects. All staff is regularly 
trained in MRI safety procedures by the Brain Imaging Center staff following University rules and procedures. 
Heating from radiofrequency (RF) pulses:  The fMRI pulse sequences that will be used are discussed prior to 
usage by the MR physicists and the director of the Center for Magnetic Resonance Imaging with respect to 
potential heating effects. The physicists at the Sharp and Children’s MRI Center regularly test pulse sequences 
on phantom objects for heating effects. 
Acoustic noise:  Subjects will wear earplugs and headsets that reduce the noise by about 20-40 dB.  Subjects 
will be instructed to indicate if the noise is a source of physical or psychological discomfort. If this occurs, the 
experiment will be terminated immediately. 
 
Blood Draw. Trained nursing staff at ACTRI (or Medical Care San Diego and LabCorp) will perform all blood 
draws (certified phlebotomists).  
 
Medical or Psychiatric Emergencies. If during the assessment procedures or any other time during the study any 
study personnel becomes aware of any medically concerning information or psychiatric emergencies. 
 
Challenge Drug Application: After application of study drugs we will assess participants’ well-being. 
Participants will be informed during the consent process about possible side effects and subjects can withdraw 
from the study at any time. Both medications have been used in single drug applications before and were well 
tolerated. Based on our exclusion criteria, no individual who took the medication in the past should be allowed 
to be in the study due to rule out of major medical illness including Parkinson's or diabetes. However, we will 
screen for lifetime use of either of those drugs to exclude the risk of allergic reaction due to prior exposure. 
 
The feasibility procedures will also include assessment of side effects from the medication. In case a study 
participant was to have a serious reaction (such as anaphylaxis) 911 would be called immediately and the 
person transported to the medical emergency room that is located about 500 yards away on campus. The study 
personnel are trained in basic life support.  
Cardiac conduction abnormalities have been noted in individuals with anorexia nervosa.  To ensure patient 
safety, we will only include patients in our study that are considered medically stable by the Medical Director at 
UC San Diego Health Eating Disorders Center for Treatment and Research (i.e. normal EKG and lab 
electrolyte values).  If the staff at those facilities does not feel their patient is stable enough to complete the 
fMRI scan, the study will be postponed until she is stable, or the patient will be withdrawn from the study if 
timing does not allow the scan to be postponed.  Study participants will have their blood pressure and heart rate 
taken prior to study drug administration as well as at the end of each study day. In case there is a significant 
drop in blood pressure indicating orthostasis during the study or due to the study medication, we will keep 
study participants in our research space and provide them with fluids and will recheck the blood pressure until 


 
 
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it has normalized. In case there were ongoing indication of orthostasis we will refer the participant to the local 
emergency room on campus. 
Electrocardiogram. The risk is minimal. Any skin irritation from the electrode placement usually lessens within 
a few minutes of removing the electrode.   
 
 
Data and Safety Monitoring Plan  
 
Data will be analyzed as above for brain imaging data. The behavioral data will be analyzed using SPSS 
statistical software on password protected computers. The PI will perform data analysis with some research 
assistant support. 
Subjects will be continuously monitored during their study participation by asking about how subjects feel and 
if they have any problems while in the study. However, in case of unexpected effects, the PI will report those to 
UCSD HRPP.  
 
Suicidal Ideation: In the proposed study populations there is the possibility of mood disturbance including 
suicide and extreme emotional distress or anxiety. The questionnaires applied will give indication about mood 
states as well as will the diagnostic procedures conducted with research staff and the PI. Those questionnaires 
and diagnostic assessments will be reviewed by the PI and any other involved study personnel will be trained to 
contact the PI immediately in case there were behavioral responses that indicate danger.  
For Healthy Control Subjects, should the PI discover suicidal ideation from their answers on the questionnaires, 
he will contact the subject directly and assess suicidality over the phone or if needed will request a health check 
up through the police department. If acute suicidality is discovered during the in person interview, then the PI 
will contact emergency medical services to escort the patient to the emergency room. For AN Subjects, the PI 
will inform the patient’s individual therapist and treatment team of suicidal ideation. Because the AN patients 
will all be in a highly supervised treatment environment, they are assessed regularly throughout the day for 
suicidal ideation. Dr. Frank will work with the patient’s therapist to determine the appropriate course of action 
which might include emergency room care if acutely suicidal.   
 
During consent procedures, participants will be informed of staff’s responsibility to report any disclosure of 
current child abuse or neglect or intent to hurt oneself or someone else to the appropriate officials. Appropriate 
services will be informed if such information regarding abuse or neglect is made available. Research staff will 
review each subject with the PI and is educated about decisions related to reporting child neglect and abuse 
and have been and will be trained to consult the hospital and/or university legal counsel if necessary for 
guidance.  
 
There will be no independent data safety monitoring board. Subject files will be stored in a research-designated 
locked file cabinet, in a locked office at UC San Diego Health Eating Disorders Center for Treatment and 
Research. All scored assessments and study results will be stored on password-protected computers and 
stripped of readily identifiable information. 
 
As a mandatory reporter, the PI will contact social services in case we learn about any current case of child 
abuse. The study population is in the adult range so this will be a less likely scenario, however, we will report 
in case we learn about child abuse.  
 
Plans for monitoring study conduct: the protocol will be conducted according to a time line. Prior to study 
initiation a detailed procedure protocol will be established and for every subject enrolled there will be the 
subject flow chart that is followed. This will ensure that all study parts will be adhered to. Each time a study 


 
 
Biomedical IRB Application Instructions 
Page 40 
part has been completed, the PI or study personnel will check off and initial. This flow chart will also serve as a 
scheduling tool with notes for upcoming study parts such as the fMRI scan.  
 
Things That Must Be Reported to the Authorities 
 
During consent procedures, participants will be informed of staff’s responsibility to report any disclosure of 
current child abuse or neglect. The scale that examines these issues is a retrospective assessment of abuse 
history current adults may or may not have been exposed to as children. Appropriate services will be informed 
if such information regarding current abuse or neglect is made available. Research staff has been, and will be 
on a continuous basis during case review with the PI, educated about decisions related to reporting child neglect 
and abuse and have been and will be trained to consult the hospital and/or university legal counsel if necessary 
for guidance. 
 
 
16. PRIVACY AND CONFIDENTIALITY CONSIDERATIONS INCLUDING DATA ACCESS AND 
MANAGEMENT 
Privacy and Confidentiality 
 
Setting. All consenting procedures will be conducted in the private offices of the PI and research staff at the UC 
San Diego Health Eating Disorders Center for Treatment and Research. The Pre-Scan Study Visit will take 
place at ACTRI (primary option) or at San Diego Medical Care or LabCorp facilities (secondary option). Study 
Visit 1, Study Visit 2, and Study Visit 3 procedures will be conducted at the Sharp and Children’s MRI Center. 
 
Safeguards to Protect Subject Confidentiality. Sensitive information about a subject's medical and psychiatric 
history including substance abuse and treatment histories are collected as part of this research study.  To protect 
the privacy we will keep all subject folders in locked file cabinets in the locked offices of the PI and research 
coordinator.  Only the PI and research staff will have access to these files.  In addition, the possible risk of loss 
of confidentiality is explained to the subject as a possible risk and he/she has the option of not participating in 
the study.  Information about current psychiatric illness and current medication use is collected as research data.  
In addition, information about drug abuse and dependence is collected as part of the study.  The patient 
populations included in this research study include participants who have been diagnosed with a medical or 
psychiatric condition.  While this information is considered sensitive, it is necessary to collect this data to 
provide an accurate description of our subject populations and use as a comparison to our healthy control 
populations.  All subjects are told in the consenting process that they can choose to not answer any question.  
While they do have the right to refuse to have this sensitive data collected, some of the sensitive data are 
necessary to collect for the outcome of the study (including substance use, medical conditions, etc.), therefore, 
the principal investigator may choose to withdraw or not include any participant who chooses to not have this 
sensitive data collected.    
 
Data Storage and Access 
When a participant enrolls in the study, a subject folder will be created that contains original documents of the 
ICF and HIPAA forms as well as all of the self-assessment forms and scan day forms. Payment information 
will also be kept in the subject folder. The folders will be kept in a locked cabinet of Dr. Frank or his research 
staff and access will be limited to his research staff working on this study. In addition, a subject number will be 
assigned to each participant and the key that contains the subject’s identity will be kept electronically in a 
password protected file by Dr. Frank’s lab manager. 
 


 
 
Biomedical IRB Application Instructions 
Page 41 
After the subject completes the study procedures (after Scan Day 2), the research staff will make a certified 
electronic copy of all of the subject’s paper data which include: Signed ICF, Consent documentation, Signed 
HIPAA Authorization, fMRI Screening Form, Race & Ethnicity Form, Contact Information Form, 
Questionnaire Packet, Scan Day Assessments, Subject Face Sheet, Subject Medication Effects Log, Lab and 
EKG Results, and Payment information. This certified electronic copy will be stored on an encrypted and 
regularly backed up server at the UC San Diego Health Eating Disorders Center for Treatment and Research 
and access to these files will be limited to Dr. Frank and his research staff. Other electronic files to be stored on 
this encrypted server (de-identified): SCID 5 assessment and brain images.  
 
The behavioral and questionnaire data will be entered into a password protected excel file. This file will contain 
no PHI.  
The brain imaging procedures will be performed at Sharp & Children’s MRI Center. This center will perform 
the scans as a fee for service facility and a Letter of Agreement will be established between the Department of 
Psychiatry at UCSD and the Sharp & Children’s MRI Center. After the completion of the MRI scans, de-
identified brain images will be transferred through CD or direct transfer to a landing site that will be created by 
the ACTRI and from there transferred to the VRD environment created for our lab by ACTRI. The data 
transferred will not contain PHI and access to the images will be restricted to Dr. Frank and his research staff.  
 
Once complete, the paper documents will be securely destroyed and only the certified electronic copy and de-
identified data will be kept.  
 
All data collected under this Research Plan will be stored on the ACTRI VRD Environment created for Dr. 
Frank and his lab.  
 
 
17. POTENTIAL BENEFITS 
 
There is no direct benefit for individuals participating in this study. However, individuals with AN participating 
in this study may benefit from the screening procedures that include a careful examination of the subject's 
psychiatric condition. They may request a copy of the in-depth diagnostic assessment that they may share with 
their provider if they wish or review with the PI.  
 
18. RISK/BENEFIT RATIO 
 
Risk/Benefit Ratio: This study involves questionnaires, in person assessments, a blood draw, EKG and 3 fMRI 
scans with administering a single dose of 2 medications and placebo to subjects and there are potential risks to 
taking the medication as outlines above.  Anorexia nervosa (AN) is the most deadly disease among the 
psychiatric disorders (Sullivan, 1995) and no medication has been approved to this date to treat the disorder.  
There is a potential benefit of investigating the concept that direct receptor acting medication can ameliorate 
excessive brain dopamine related reward response in AN and thus could in fact become an important treatment 
for this disorder; therefore, we feel the potential benefits outweigh the risks involved in this pilot study.   
 
Importance of the knowledge to be gained 
 
The results from this project will  
(1) provide information on how feasible brain imaging and dopamine challenge drug application is in anorexia 
nervosa. 


 
 
Biomedical IRB Application Instructions 
Page 42 
(2) provide important new information on how dopamine D2 receptors are involved in prediction error response 
and reversal learning within anorexia nervosa and healthy control groups.  
(3) provide pilot data whether healthy controls or individuals with anorexia nervosa can be distinguished by 
dopamine receptor-driven brain response. 
 
Anorexia Nervosa has the highest mortality rate among the psychiatric disorders and is associated with an 
immense amount of suffering for the patients and their families. The results of this study will help us identify 
how dopamine receptor function is involved in altered brain activation and behavior response in anorexia 
nervosa. What this may help is identify targets for pharmacological intervention. We believe that the benefits of 
the study by far outweigh the potential risks. 
 
19. EXPENSE TO PARTICIPANT 
None 
20. COMPENSATION FOR PARTICIPATION 
Questionnaire Packet & Initial Screenings: $25 
Diagnostic Assessment: $25 
Pre-Scan Study Visit: $25 
Study Visit 1, 2, 3: $150/Study Visit  
Reimbursement for Parking at ACTRI Pre-Scan Visit: $5 
 
Total Compensation for Study: $530 
Although rare, it is possible that the MR scanner may have errors or problems or there are personnel issues, or 
problems with the taste pump, etc. that prevent us from completing the scheduled study visit day. Sometimes 
these issues are not known until the start of the scan after the subject has already completed many of the 
questionnaires, taste test, etc. If the timing of the scan allows us to reschedule one/both of the Study Visits, we 
will ask the subject if they are willing to come back to complete an additional study visit day and will 
compensate them $100 for the incomplete study visit in additional to the amount they receive for the regular 
study procedures.  
Ineligible subjects or subjects who withdraw from the study prior to Study Visit 1 will receive an electronic gift 
card in the amount of $25, $50 or $75 (depending on what stage of the study the subject completed) to Amazon 
or Target. 
In the consent form the subject is informed that compensation in this study is considered taxable income and 
after the subject passes the Screening Visit, the subject will be given instructions on how to register herself on 
Payment Compass. The subject will be reminded that research staff will submit a request for payment to UCSD 
after they complete the study and that if they are excluded or withdraw prior to the first MRI scan (Study Visit 
1), they will be compensated in the form of an electronic gift card.  
If a subject did not choose to register herself on Payment Compass (or those individuals who do not have easy 
access to complete the Self-Registration process on Payment Compass, such as AN subject in a treatment 
program with limited internet access), we will have the subject complete a paper W9 form with their social 
security number and contact information. The research staff will then register the subject in Payment Compass 
and submit the payment request to UCSD after the completion of the study.  
The payment is to serve as an incentive for subject participation and to reimburse travel, study time and 
expenses. Although the individual subject may not receive any benefit beyond financial remuneration, the data 


 
 
Biomedical IRB Application Instructions 
Page 43 
generated by this project could significantly enhance our knowledge about altered brain function with respect to 
anorexia nervosa and pave the way for new clinical measures and treatments for those disorders. 
21. PRIVILEGES/CERTIFICATIONS/LICENSES AND RESEARCH TEAM RESPONSIBILITIES 
 
Principal Investigator: Dr. Frank, MD will serve as the Principal Investigator on this study. As the individual 
who is primarily responsible for the study he will oversee all aspects of research including regulatory, grant 
submissions, recruitment, consenting, study procedures, data entry and data analysis. Dr. Frank is employed by 
UCSD and is funded through the R21 grant of this study.  
 
Lab Manager: Ms. Megan Shott, BS, will serve as the Lab Manager for Dr. Frank. She will oversee the day to 
day tasks of the lab and this protocol including recruitment, consenting, study procedures training and 
administration, data entry, and data analysis. She will also be responsible along with Dr. Frank to ensure the 
study meets all regulatory requirements and ensure that all staff members have adequate training to run the 
study. Dr. Frank may assign Ms. Shott other duties via the Delegation of Duties Log. Ms. Shott is employed by 
UCSD and is funded through the R21 grant of this study.  
 
Staff Research Associates and students (TBD). Dr. Frank may employ one or more staff research associates or 
students who will be responsible for recruitment, running study procedures and data entry as well as other 
duties assigned by Dr. Frank via the Delegations of Duties Log.  These individuals will be employed by UCSD 
and funded through the R21 grant of this study.  
 
Skylar Swindle, BS, will act as a staff research associate and will be responsible for recruitment, running study 
procedures and data entry along with other duties assigned by Dr. Frank via the Delegations of Duties Log. She 
is employed by UCSD and funded through the R21 grant of this study.  
 
 
 
22. BIBLIOGRAPHY 
Admon, R., Kaiser, R.H., Dillon, D.G., Beltzer, M., Goer, F., Olson, D.P., Vitaliano, G.,Pizzagalli, D.A., 2017. 
Dopaminergic Enhancement of Striatal Response to Reward in Major Depression. American Journal of 
Psychiatry 174(4), 378-386. PMC5378658. Access Number: 27771973. 
Cools, R., Frank, M.J., Gibbs, S.E., Miyakawa, A., Jagust, W.,D'Esposito, M., 2009. Striatal dopamine predicts 
outcome-specific reversal learning and its sensitivity to dopaminergic drug administration. Journal of 
Neuroscience 29(5), 1538-1543. PMC2940719. Access Number: 19193900. 
Holt, R.I., Barnett, A.H.,Bailey, C.J., 2010. Bromocriptine: old drug, new formulation and new indication. 
Diabetes Obes Metab 12(12), 1048-1057. Access Number: 20977575. 
Kaye, W.H., Wierenga, C.E., Bailer, U.F., Simmons, A.N.,Bischoff-Grethe, A., 2013a. Nothing tastes as good 
as skinny feels: the neurobiology of anorexia nervosa. Trends in Neurosciences 36(2), 110-120. 
PMC3880159. Access Number: 23333342. 
Rosenzweig, P., Canal, M., Patat, A., Bergougnan, L., Zieleniuk, I.,Bianchetti, G., 2002. A review of the  
pharmacokinetics, tolerability and pharmacodynamics of amisulpride in healthy volunteers. Hum 
Psychopharmacol 17(1), 1-13. Access Number: 12404702. 
 
 
23. FUNDING SUPPORT FOR THIS STUDY 
This study is funded by the National Institute of Mental Health R21MH120475. Project Period: 8/1/2019 – 
4/30/2021.  
UCSD Fiscal Staff Info:  


 
 
Biomedical IRB Application Instructions 
Page 44 
Fnu Clarissa 
Fund Manager 
Department of Psychiatry, University of California San Diego 
fclarissa@ucsd.edu 
858.534.4788 
 
24. BIOLOGICAL MATERIALS TRANSFER AGREEMENT 
Not applicable. 
 
25. INVESTIGATIONAL DRUG FACT SHEET AND IND/IDE HOLDER 
Drug Names: Bromocriptine mesylate; Amisulpride 
IND #: 191908 
IND holder: Guido K.W. Frank 
 
Dr. Frank and the Lab Manager will be responsible for monitoring the study in the following ways:  
 
Medication Handling and Storage 
• Per 21CFR §312.6   Labeling of an investigational new drug, medications will be stored in a locked 
cabinet in the research office of the PI. That office is embedded in the UCSD Eating Disorder Research 
Program office suite, which is locked. Each study drug will be labeled with the statement “Caution: 
New Drug—Limited by Federal (or United States) law to investigational use.”  
• Per 21CFR §312.61 Control of the investigational drug, the investigator will not supply the 
investigational drug to any person not authorized under this part to receive it. 
 
Subject Level 
• Dr. Frank will review all Pre-Scan Blood Test and EKG results to ensure subject’s medication risks are 
minimized.  
• Research staff will complete symptom checklist on each Study Visit day and will document the 
following: Documentation of blood pressure & heart rate pre-medication administration and post scan; 
symptom checklist including: nausea, headache, dizziness, tiredness, other. Research Staff will report 
these values to Dr. Frank and the Lab Manager at the end of the Study Visit.  
• Research staff will contact Dr. Frank and/or Lab Manager via phone if there is a significant drop in 
blood pressure (20 or more points systolic) after the medication administration or significant symptoms 
that the subject feels keep her from continuing the study.  
• Dr. Frank or Lab Manager will confirm with research team that all unexpected or adverse events 
(AEs/SAEs) have been reported to the IRB and FDA in the required timeframe.  
• Dr. Frank or Lab Manager will review each subject folder after the subject completes the study to 
ensure required documentation and procedures have been completed.    
 
Study Level 
• The Lab Manager will prepare monthly aggregate reports of the adverse events, serious adverse events, 
and unexpected events and will review with Dr. Frank.  
• Dr. Frank will review monthly aggregate reports to determine safety of the study medications and 
whether the study is safe to be continued.  
 
Per FDA Approval, Dr. Frank will be responsible for the following reporting requirements:  
 


 
 
Biomedical IRB Application Instructions 
Page 45 
• Dr. Frank will report any unexpected fatal or life-threatening suspected adverse reactions to FDA no 
later than 7 calendar days after initial receipt of the information.  
• Dr. Frank will report any 1) serious, unexpected suspected adverse reactions, (2) findings from other 
clinical, animal, or in-vitro studies that suggest significant human risk, and (3) a clinically important 
increase in the rate of a serious suspected adverse reaction to FDA no later than 15 calendar days after 
determining that the information qualifies for reporting.  
• Dr. Frank will submit annual progress reports within 60 days of the anniversary of the date that the IND 
became active. 
 
26. IMPACT ON STAFF 
ACTRI research nursing staff will perform the blood draws and EKG for subjects on the Pre-Scan Study Visit. 
Each staff member will be trained in phlebotomy and EKG procedures. If the secondary option is chosen for the 
Pre-Scan Study Visit, staff members at these facilities will be trained in EKG and phlebotomy procedures by 
their respective facility.  
27. CONFLICT OF INTEREST 
The PI and key research staff have no conflicts of interest or financial disclosures to declare.  
28. SUPPLEMENTAL INSTRUCTIONS FOR CANCER-RELATED STUDIES 
Not applicable 
 
29. OTHER APPROVALS/REGULATED MATERIALS 
Not applicable  
 
30. PROCEDURES FOR SURROGATE CONSENT AND/OR DECISIONAL CAPACITY 
ASSESSMENT 
Not applicable 
 
 
 
 

ICF_001.pdf: 
UCSD Project 191348 
 
 
Page 1 of 15 
Version Date: 03/03/21 
form version 12/19/18 
 
University of California, San Diego 
Consent to Act as a Research Subject 
 
Toward understanding dopamine receptor contributions to prediction error and reversal learning in 
anorexia nervosa 
 
Introduction 
 
Dr. Guido K.W. Frank is conducting this research and asking for your consent to participate. This 
section provides a summary of important information. The rest of the form provides additional 
details. 
 
• Research is voluntary- whether or not you join is your decision. You can discuss your 
decision with others (such as family, friends or another physician).  
• You can say yes but change your mind later. 
• If you say no, we will not hold your decision against you. 
• Your decision will not affect your health care or any other benefits you may be entitled to. 
• You can say no even if the person inviting you is part of your healthcare team.  
• Please ask questions or mention concerns before, during or after the research. 
 
We are trying to learn more about the impact of medication on the brain reward systems.  We are 
trying to gain more information about what happens in the brain when we receive so called rewards, 
that is things people usually like and look forward to, and how medication may enhance or diminish 
the brain’s response to these rewards.  This study may better help us understand treatments for 
anorexia nervosa.  
 
You will first undergo several procedures to determine if you are eligible for the study including 
questionnaires, interviews, and blood tests. If you are eligible, you will be scheduled for 3 MRI 
brain scans spaced about 3 days apart. Before each scan, you will take a study medication, eat a 
standardized breakfast, complete questionnaires and then complete a brain scan that lasts about one 
hour where you will receive sweet and neutral taste solutions and play a learning game. Each study 
visit day will last up to 4 hours.   
The most commonly expected risks of the study are discomfort from filling out the questionnaires 
and being in the MRI scanner for about an hour. The most commonly expected medication risks of 
the study are feeling tired or dizzy.  
 
The most serious risks of the study may include allergic reaction to the study medications or a low 
heartbeat. The likelihood of this occurring after one single administration of the drug is very low 
and we will exclude individuals with risk factors for those conditions .  
 
This is not a treatment study. The only alternative is not to participate in the study. 
 


UCSD Project 191348 
 
 
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Please take your time to make your decision. Discuss it with your family. Additional, detailed 
information about this research is provided below. Please feel free to ask questions before signing 
this consent. 
 
 


UCSD Project 191348 
 
 
Page 3 of 15 
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Why have you been asked to participate, how you were selected, and what is the 
approximate number of participants in the study? 
You have been asked to participate in this study because you are a healthy control and at normal 
weight or you are underweight and struggle with anorexia nervosa. There will be approximately 104 
participants in this study.  
 
 
How much time will each study procedure take and how long will the study last? 
You will be in the study for up to 3 months (depending on scheduling). This will include the initial 
phone screening, questionnaire packet, psychiatric assessment, blood draw, electrocardiogram 
(EKG) and 3 MRI scans spaced about 3 days apart.   
 
You can stop participating at any time. However, if you decide to stop from participating in the 
study, we encourage you to talk to the research doctor.  
 
 
What will happen to you in this study and which procedures are standard of care and which are 
experimental? 
In addition to the information at the beginning of this form, here are some additional details about 
will happen to you if you agree to be in this study.   
 
If after initial screening, you are invited to join the study, and if you provide your Informed Consent 
on this Form, then you will be assigned to one of two groups.  
 
• The first group will consist of persons with anorexia nervosa. Anorexia nervosa is an eating 
disorder associated with intense fear of weight gain, food refusal, and severe weight loss. 
• The second group, which we call a control group, will consist of persons who are within 
average weight range and appear to be in generally good health.  
 
If you are recruited from the community, you will participate in 2 phone calls at the beginning of 
the study.   
• At the first phone call, we will ask you some basic questions about your physical condition 
and general health as well as review the consent form with you (10 minutes).   
• If you qualify and agree to participate further in the research, we will mail you a paper copy 
of the consent and several questionnaires to complete (it will take about an hour to complete 
the questionnaire packet).  
• When we receive the questionnaires back, you will get a second phone call from us where 
we will let you know if you qualify and can continue in the study.  If you don’t or if we 
don’t hear back from you in 3 months, any information we collected about you will be 
destroyed.   
• If you qualify and agree to go on with the study, we may do one more screening 
questionnaire with you at the second phone call (about 30 minutes).  If you qualify and agree 
to continue in the research, we will schedule an in person visit.   
 


UCSD Project 191348 
 
 
Page 4 of 15 
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If you are recruited from UC San Diego Health Eating Disorders Center for Treatment and 
Research, we will ask you screening questions in person when we meet with you.  
• If you qualify and agree to participate further in the research, we will provide you with a 
paper copy of the consent and several questionnaires to complete (it will take about an hour 
to complete the questionnaire packet).  
• When we receive the questionnaires back, we will meet you in your treatment program or 
call you to let you know if you qualify and can continue in the study.   
• If you qualify and agree to go on with the study, we may do one more screening 
questionnaire.   
 
 
If you join the study, you will complete the following:   
 
1. Screening and Assessment (Screening Visit, 60 to 90 minutes, in-person) 
• We will ask you about your psychiatric and medical history before entering the study. Here 
we will ask you questions about what illness you may have had. We will also ask you 
personal questions about how you have been feeling including questions about any times 
when you may have been depressed or gotten very anxious or afraid of certain situations. 
You will be asked questions about trauma that may have occurred to you. You may decline 
to answer any questions.  
• In addition, we will ask you about your drug and medication history. If you are taking 
certain medications, you may not be able to participate in this study. Throughout your 
participation in this study, it is important that you do not drink any alcoholic beverages or 
take any drugs or medications unless you notify the research investigators.  
• We will have you complete a swallow test to make sure that you will not have difficulty 
swallowing the study medication. For this, you will be given an empty medication capsule 
that will be the same size as the one you will take the morning of each Study Visit.  
• If you qualify for the study, you will be scheduled for the brain imaging study.  
 
2. Pre-Scan Blood Draw and Electrocardiogram(EKG) (Pre-Scan Visit, 60 minutes, in-person) 
In order to make sure it is safe for you to have the study medication and complete the MRI scans, 
you will be asked to complete a Pre-Scan Visit no more than one week before your scheduled Study 
Visit 1. At this visit you will be asked to complete the following:  
 
• A blood draw that will measure your electrolyte and kidney function. It will also tell us if 
you are pregnant (about 2 tablespoons of blood will be taken).   
• An electrocardiogram (EKG) that will measure the electrical activity in your heart. For this 
procedure sensors (electrodes) will be placed on your chest and limbs and the machine will 
measure the electrical activity of your heart.  
 
If you have abnormal test results you may be withdrawn from the study.  
 
3. Brain Imaging Study (Study Visit 1, Study Visit 2, Study Visit 3; 4 hours each study visit, in-
person) 


UCSD Project 191348 
 
 
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You will complete 3 brain scans that are spaced about 2 – 4 days apart.    
The brain scans are done using a machine called magnetic resonance imaging (MRI) scanner. This 
is a large magnet that can be used to study the brain. This type of machine is very commonly used 
in hospitals to detect whether someone has an injury for instance in the brain or other body parts. 
This procedure does not involve any radiation and is seen as very safe.  
• On the morning of each of the brain imaging studies, we ask you to be at the Sharp and 
Children’s MRI Center, 7910 Frost St Suite 110, San Diego, CA 92123, between 6 to 7 am.   
• A urine pregnancy test will be conducted on Study Visit 1 regardless if you believe there is 
any possibility of you being pregnant. If you are pregnant or nursing, you will not be able to 
participate in this study. 
• After you complete the pregnancy test and if the test is negative, you will be asked to take 
one of the study medications (placebo, amisulpride, or bromocriptine; order is randomized).  
The Principal Investigator and research staff are blinded to which medication you will be 
given on each Study Visit.  The order in which you will receive the study medication the 
morning of the scan will be assigned by chance. Neither you nor the researcher can choose 
the order to which you will receive the medications. The research staff will administer the 
oral medication at the start of your breakfast and the fMRI scan will begin three hours later.  
• We will provide you with a standard breakfast or you will eat according to your meal plan if 
you are in an eating disorder treatment program.  
• You will be asked to complete several questionnaires that ask about your mood, food 
cravings, and eating behaviors.  
• You will be asked to test sugar solutions rate those for your personal sweetness and 
pleasantness experience. You will be testing various sugar solution strengths. In order to test 
that, you will be presented with 9 small samples of the solutions with about ½ teaspoon (2 
ml) that you will swallow.  The test for solutions will take about 10 minutes.  
• Prior to each MRI scan you will be familiarized with tubes that deliver taste stimuli to your 
mouth. You will be shown how to position the tubes in your mouth and to wipe your tongue 
once around in your mouth after each taste application. You cannot participate in the MRI 
part of the study if you have difficulty with this procedure. 
• A picture of your brain will be obtained using a Magnetic Resonance Imaging Scanner. One 
type of picture called MR scan will show us the anatomy of your brain. The other pictures 
show us how much blood is flowing through your brain during the time in the brain 
scanning machine. 
o For this, you will be placed in a large donut-like machine (MR scanner). 
o The scanning will take about 60 minutes. 
o Your head will be placed in a special helmet-like “head-holder” to keep your head 
still. 
During each MRI scan, you will be asked to complete several computerized tasks: 
• You will be asked to hold the taste tubes in your mouth.  At various intervals, small 
amounts (1 ml, which is about 1/5 of a teaspoon) of liquids of either sugar water or a 
tasteless solution will be delivered into your mouth. Before each taste solution you will 
see an abstract colorful picture on goggles that you are wearing in the scanner and you 
will be asked to predict what solution will follow each abstract picture by pressing a 
button on a button box. This task will take 28 minutes. 


UCSD Project 191348 
 
 
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• You will be asked to play a game where you will learn rules what buttons to push in 
response to visual cues. These rules will change throughout the task. This task will take 
about 20 minutes.  
 
Altogether, assessments will take about 3 hours, the blood draw and EKG will take about an hour 
and each brain imaging session including breakfast and questionnaires will take about 4 hours. Total 
study duration therefore is about 16 hours on 5 different study days over about 2 weeks. 
 
Study Procedures Chart (Subjects from Community) 
 
  
Initial 
Screening 
(Phone) 
Detailed 
Eligibility 
Screen 
(Phone) 
Screening 
Visit (In-
Person) 
Pre-Scan 
Visit (In-
Person 
Study 
Visit 1 
(In-
Person) 
Study 
Visit 2 
(In-
Person) 
Study 
Visit 3 
(In-
Person 
Initial 
Screening 
X 
  
  
  
  
  
  
Informed 
Consent 
(through mail) 
  
X 
  
  
  
  
  
Questionnaire 
Packet (through 
mail) 
  
X 
  
  
  
  
  
Biological 
Screening Form   
X 
  
  
  
  
  
In-Person 
Consent and 
Meeting with PI 
  
  
X 
  
  
  
  
Mental Health 
Interview 
  
  
X 
  
  
  
  
Medication 
Swallow Test 
 
 
X 
 
 
 
 
Blood Tests & 
EKG 
  
  
  
X 
  
  
  
Pregnancy Test 
  
  
  
  
X 
  
  
Taste Test 
  
  
  
  
X 
X 
X 
MRI Scan 
  
  
  
  
X 
X 
X 
Scan 
Questionnaires 
  
  
  
  
X 
X 
X 
 
 


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Study Procedures Chart (Subjects from UC San Diego Health Eating Disorders Center for 
Treatment and Research 
 
  
Consent 
Visit 
Screening 
Visit 
Pre-Scan 
Visit 
Study 
Visit 1 
Study 
Visit 2 
Study 
Visit 3 
Initial Screening 
X 
  
  
  
  
  
Informed 
Consent 
X 
  
  
  
  
  
Questionnaire 
Packet 
  
X 
  
  
  
  
Consent and 
Meeting with PI  
  
X 
  
  
  
  
Mental Health 
Interview 
  
X 
  
  
  
  
Medication 
Swallow Test 
 
X 
 
 
 
 
Blood Tests & 
EKG 
  
  
X 
  
  
  
Pregnancy Test 
  
  
  
X 
  
  
Taste Test 
  
  
  
X 
X 
X 
MRI Scan 
  
  
  
X 
X 
X 
Scan 
Questionnaires 
  
  
  
X 
X 
X 
 
 
Additional Optional Procedures 
 
The following are additional optional study procedures that you are being asked to consider.  You 
may choose to participate in any, or none, of the following procedures.  Your decision to 
participate, or to not participate, in these additional procedures will not affect your ability to 
participate in the main study you agreed to above. 
 
 
Consent to be Contacted for Future Research Studies (Optional) 
 
There may be future studies that you are eligible to participate in. Please initial below whether you 
agree or do not agree for us to contact you about participating in future studies.    
 
Initial next to your choice: 
 


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_____  I agree to be contacted for future research 
 
 
_____  I do not agree to be contacted for future research 
 
 
Consent to Allow the Research Team to Share your Information with UC San Diego Health Eating 
Disorders Center for Treatment and Research (Optional) 
 
You may also opt-in to allowing the research team to share your information in the following 
manner below. 
 
Initial next to your choice: 
 
_____  I agree to allow the data collected to be shared with my health provider at UC San Diego 
Health Eating Disorders Center for Treatment and Research (e.g. to assist clinicians and treatment 
teams in assessing which strategies might be most effective based on your current measures). 
 
_____  I do not agree to allow the data collected to be shared with my health provider at UC San 
Diego Health Eating Disorders Center for Treatment and Research (e.g. to assist clinicians and 
treatment teams in assessing which strategies might be most effective based on your current 
measures). 
 
Initial next to your choice: 
 
_____  I agree to allow the data collected to be shared with researchers/research teams at UC San 
Diego Health Eating Disorders Center for Treatment and Research for use in other eating disorder 
research studies. 
 
_____  I do not agree to allow the data collected to be shared with researchers/research teams at UC 
San Diego Health Eating Disorders Center for Treatment and Research for use in other eating 
disorder research studies. 
 
 
What risks are associated with this study? 
Participation in this study may involve some added risks or discomforts. In addition to the risks 
described at the beginning of this form.  
 
1. Risk of filling out the questionnaires 
 
You may experience some psychological discomfort or fatigue when filling out questionnaires. You 
do not have to complete the questionnaires in one sitting. You can choose not to answer any 
question that makes you uncomfortable.  
 
2. Risks of the scanner 


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While in the scanner, you may experience a gagging response or nausea/gastrointestinal discomfort 
to certain tastes.  
 
If you are uncomfortable with the testing procedure, the study can be stopped at any time. If we 
discover that you describe emotional distress, then we will evaluate if you are in need for a referral 
for professional help. Such a referral may range from counseling to referral to the authorities for 
emergency treatment. 
 
3. Risk of loss of confidentiality 
 
Some of the information collected, e.g. whether you have used illegal substances, were to become 
public, it may place you at risk for criminal or civil liability or may be damaging to your ability to 
get a job, affect your personal reputation, or have otherwise unforeseen consequences.   
In order to minimize this risk, all of your data will be kept in locked cabinets or in databases with 
secured passwords with access restricted to the PI and his research staff.  
 
4. Risk of an MRI 
 
You should NOT have an MRI if you have metal or electronic devices inside your body.   
Heart pacemakers and insulin pumps are examples of electronic devices. 
The most common side effects of having an MRI are the following 
• You may experience flashing lights in the eyes.  This is caused by the magnetic waves and is 
not harmful.  This usually goes away after a few minutes.  
• There is a risk of muscular aches from lying on your back for a total amount of about 60 
minutes in the scanner.  
• Banging noises that the MRI machine makes while taking pictures of your brain are loud. 
You will be wearing headphones and ear plugs to minimize this noise. 
• Muscle twitches during the magnetic resonance imaging procedure may occur.  
• There are no known harmful effects from the magnetic resonance imaging, but some people 
undergoing this procedure may become anxious and afraid of closed spaces.  If this happens 
to you, you can stop this procedure at any time.   
• If you are pregnant or think you may be pregnant, you should not take part in this research.  
If you have any metal clips or plates in your body or a pacemaker, you should tell the 
investigator about it. We will carefully screen you for any metal in your body. 
 
Before going into the scanner we will carefully screen you to make sure you are safe to have an 
MRI scan. Before the scan starts we will give you pillows and a blanket to make you more 
comfortable. The ear plugs and headphones will muffle the noise and protect your ears. We will 
check on you throughout the scan to make sure that you are comfortable and will give you a buzzer 
that alerts us of an issue. You can stop the scanning procedures at any time.  
 
 
5. Risk of Medication 


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Bromocriptine. This medication is used to treat Parkinson’s Disease and Type 2 diabetes. It has 
previously been used in brain imaging studies like this.  
The most common risks from using this medication for prolonged use include: nausea, 
headache, stomach upset, dizziness, drowsiness, feeling faint or fainting, and suddenly falling 
asleep. 
Serious side effects from using this medication for prolonged use can include: heart attack, 
stroke, and pulmonary fibrosis (lung disease). 
After the one-time application you might feel at most some nausea, headache or dizziness.  The 
other side effects are in the context of prolonged prescription and not after single dose which the 
study will use.  
Certain conditions may interact with this medication. You should let your study doctor know if 
you have syncopal migraines (experience fainting with migraines), uncontrolled hypertension 
(high blood pressure), pheochromocytoma (adrenal gland tumor), prolactinoma (overproduction 
of the hormone prolactin from a noncancerous pituitary tumor), breast cancer or a 
hypersensitivity or allergy to bromocriptine. You should let your study doctor know if you have 
a history of long QT syndrome (heart rhythm condition that can potentially cause fast, chaotic 
heartbeats) or family history of sudden death or long QT syndrome. If you have a history of 
seizures or seizure disorder you will not be included in the study.  
 
Amisulpride.  This medication has been used in Europe as an antipsychotic medication.  It has 
previously been used in brain imaging like this in the US.   
The most common risks from using this medication for prolonged use include: fever, excessive 
sweating, change in heart rate, chest pain, swelling, pain, and redness in the legs, increased 
frequency of infections, skin allergy, seizures, restless legs, twitches in the tongue and face, 
trembling, excessive salivation, constipation, decreased libido (sex drive), weight gain, 
amenorrhea (absence of menstruation), agitation or anxiety, tardive dyskinesia (a condition that 
causes involuntary repetitive movements) and neuroleptic malignant syndrome (disease that 
affects the nervous system and causes symptoms like a high fever and muscle stiffness).  
After the one-time application you might feel at most some nausea. 
 
Certain conditions may interact with this medication. You should let your study doctor know if 
you have pheochromocytoma, prolactinoma, Parkinson’s Disease, breast cancer or a 
hypersensitivity or allergy to amisulpride. 
 
We will carefully monitor you throughout the Study Visit. We will measure your blood pressure 
and heart rate and will check for any symptoms of an adverse reaction to the medication. If these 
symptoms do not go away, we will get you emergency care as needed.  
 
6. Risk of blood draw 


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In this study we will need to get about 2 tablespoons of blood from you. A certified phlebotomist 
will get blood by putting a needle into one of your veins and letting the blood flow into a glass tube.  
You may feel some pain when the needle goes into your vein.  A day or two later, you may have a 
small bruise where the needle went under the skin. There is also a slight possibility of infection. The 
phlebotomist will apply pressure to the needle site in order to reduce the possibility of bruising.  
 
 
7. Risk of Electrocardiogram (EKG) 
 
There is a small risk that you will get a skin rash where electrodes are placed.  
 
 
There may be risks associated with this study, which are currently unforeseeable.  
 
For more information about these risks and side effects, ask your study doctor.  
 
Should we identify during the screening process or interviews an acute danger to others or yourself 
we will be obligated to contact emergency services or the police department to ensure that you are 
safe.  
 
Are there risks to the reproductive system or a developing fetus? 
The effects of the MRI procedures and medications may pose some unforeseeable risks to a 
developing fetus. For this reason, participants in this investigational study should not become 
pregnant and we require that all participants take a serum pregnancy test the week before the first 
MRI and a urine pregnancy test the morning of Study Visit 1 before the MRI scan. If you have a 
positive pregnancy test, we will withdraw you from the study. If you become pregnant or if there is 
any chance of pregnancy (e.g., late menstrual period), please contact the study personnel 
immediately so that we may provide medical assistance and counseling. 
 
 
What benefits can be reasonably expected? 
There are no known benefits to taking part in the study. This study is designed for the researcher to 
learn more about how the brain responds in individuals with anorexia nervosa compared to normal 
weight individuals when getting rewards that are usually considered pleasant and the effect of 
medication on this brain response. This study is not designed to treat any illness or to improve your 
health.  Also, there may be risks, as discussed in the section describing the discomforts or risks.    
 
 
What happens if you change your mind about participating? 
If you decide that you no longer wish to continue in this study, you may contact Dr. Frank or his 
research staff.  
 
You will be told if any important new information is found during the course of this study that may 
affect your wanting to continue. 


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Can you be withdrawn from the study without your consent? 
The study doctor may decide to stop your participation without your permission if the study doctor 
thinks that being in the study may cause you harm, or for any other reason. You may also be 
withdrawn from the study if you do not follow the instructions given you by the study personnel. 
 
 
Will you be compensated for participating in this study? 
In compensation for your time and travel: 
 
• You will be paid $25 for the Questionnaire Packet and Initial Screenings.  
• You will be paid $25 for the Psychiatric Interview. 
• You will be paid $25 for the Blood Draw & EKG. 
• You will be paid $150 for each MRI Scan/Study Visit.   
• You will be reimbursed up to $5 for parking for the Pre-Scan Visit. 
 
This will add up to a total of $530 if you complete all the visits. If you leave the study early, or if 
we have to take you out of the study, you will be paid only for the visits you have completed. 
 
If there are any issues that arise after you have arrived at the MRI Center on the day of your Study 
Visit (such as a problem with the MRI machine) that require rescheduling the Study Visit, we will 
compensate you an additional $100 for your time.  
 
If you are excluded prior to Study Visit 1, your compensation will be in the form of an electronic 
gift card to Amazon or Target.  
 
It is important to know that payments for participation in a study is taxable income and we will 
report your compensation to the IRS. If you are excluded or stop your participation in the study 
prior to completing the first MRI Scan/Study Visit, it will not be necessary for us to report your 
electronic gift card amount to the IRS. 
 
 
Are there any costs associated with participating in this study? 
There will be no cost to you for participating in this study. 
 
 
What if you are injured as a direct result of being in this study? 
If you are injured as a direct result of participation in this research, the University of California will 
provide any medical care needed to treat those injuries. The University will not provide any other 
form of compensation to you if you are injured. You may call the Human Research Protections 
Program Office at 858-246-HRPP (858-246-4777) for more information about this, to inquire about 
your rights as a research subject or to report research-related problems. 
 


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What about your confidentiality? 
Research records will be kept confidential to the extent allowed by law. Every reasonable effort will 
be made to keep your records confidential. All data will be kept in a locked file cabinet only 
accessible to the study team, and on a password protected computer. All direct identifying 
information such as name and medical record number will be destroyed at the end of the study.  
 
While you are in this study all related records may be made available to: 
 
• The funding sponsor (National Institute of Mental Health) 
• The UCSD Institutional Review Board (for the protection of human subjects in research) 
• Other regulatory agencies responsible for overseeing research, such as the federal Office for 
Human Research Protections 
• The Food and Drug Administration (FDA) 
• The study doctor and his research team 
 
This research is covered by a Certificate of Confidentiality from the National Institute of Mental 
Health (NIMH). Researchers with this Certificate may not disclose or use information, documents, 
or biospecimens that may identify you in any federal, state, or local civil, criminal, administrative, 
legislative, or other action, suit, or proceeding, or be used as evidence unless you have consented 
for this use. Information, documents, or biospecimens protected by this Certificate cannot be 
disclosed to anyone else who is not connected with the research unless there is a federal, state, or 
local law that requires disclosure (such as to report child abuse, elder abuse, intent to hurt self or 
others, or communicable diseases), you have consented to the disclosure, including for your medical 
treatment; or it is used for other scientific research, as allowed by federal regulations protecting 
research subjects. 
 
The Certificate cannot be used to refuse a request for information from personnel of federal or state 
government agency sponsoring the project that is needed for auditing or program evaluation by the 
National Institute of Mental Health, which is funding the project or for information that must be 
disclosed in order to meet the requirements of the Food and Drug Administration (FDA). You 
should also understand that a Certificate of Confidentiality does not prevent you from voluntarily 
releasing information about yourself or your involvement in this research. If you want your research 
information released to an insurer, medical care provider, or any other person not connected with 
the research, you must provide consent to allow the research to release it. 
 
The Certificate of Confidentiality will not be used to prevent disclosure for any purpose you have 
consented to in this informed consent document including research data in the medical record. 
 
Under California law, we must report information about known or reasonably suspected incidents of 
abuse or neglect of a child, dependent adult or elder including physical, sexual, emotional, and 
financial abuse or neglect. If any investigator has or is given such information, he or she may be 
required to report such information to the appropriate authorities. 
 


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Personal identifiers will be removed from the information or biospecimens collected as part of the 
research. After such removal, the information or biospecimens could be used for future research 
studies or distributed to another investigator for future research studies without your additional 
informed consent.  
 
Biospecimens (such as blood, tissue, or saliva) collected from you for this study and/or information 
obtained from your biospecimens may be used in this research or other research, and shared with 
other organizations. You will not share in any commercial value or profit derived from the use of 
your biospecimens and/or information obtained from them. 
 
If the study results are published or presented, you will not be identified. 
 
A description of this clinical trial will be available on http://www.ClinicalTrials.gov, as required by 
U.S. Law. This Website will not include information that can identify you. At most the Website will 
include a summary of the results. You can search this Website at anytime.  
 
 
Will you receive any results from participating in this study? 
You may request a copy of the in-depth psychiatric interview from the investigator, which may be 
helpful to your treatment provider. You may also request to review this interview with the PI. You 
will not receive any other results from participating in this study.  
 
 
Who can you call if you have questions? 
This study has been explained to you and your questions have been answered. If you have other 
questions or research-related problems, you may reach Dr. Guido Frank at 858-246-2053.  
 
You may call the Human Research Protections Program Office at 858-246-HRPP (858-246-4777) 
to inquire about your rights as a research subject or to report research-related problems. 
 
 
Your Signature and Consent 
You have received a copy of this consent document and a copy of the “Experimental Subject's Bill 
of Rights” to keep. 
 
You agree to participate. 
 
 
_____________________________________________________  
_______________ 
Subject's signature 
 
 
 
 
 
 
 
Date 
 
 
_________________________________________________ 
_______________ 
Signature of the person conducting  
 
 
 
 
Date 
the informed consent discussion 
 


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SUBJECT’S BILL OF RIGHTS 
 
It is important that the purpose and procedures of the research study are fully understood and that 
consent is offered willingly. A subject in a research study or someone, who is asked to give consent 
on behalf of another person for such participation, has the right to the following: 
 
1. 
Be informed of the nature and purpose of the research. 
 
2. 
Be given an explanation of all procedures to be followed and of any drug or device to be 
used. 
 
3. 
Be given a description of any risks or discomforts, which can be reasonably expected to 
result from this research study. 
 
4. 
Be given an explanation of any benefits, which can be reasonably expected to the subject as 
a result of this research study. 
 
5. 
Be informed of any appropriate alternative procedures, drugs, or devices that may be 
advantageous and of their relative risks and discomforts. 
 
6. 
Be informed of any medical treatment, which will be made available to the subject if 
complications should arise from this research. 
 
7. 
Be given an opportunity and encouraged to ask any questions concerning the study or the 
procedures involved in this research. 
 
8. 
Be made aware that consent to participate in the research may be withdrawn and that 
participation may be discontinued at any time without affecting continuity or quality of 
medical care. 
 
9. 
Be given a copy of the signed and dated written consent form. 
 
10. 
Not be subjected to any element of force, fraud, deceit, duress, coercion, or any influence in 
reaching the decision to consent or to not consent to participate in the research. 
 
 
If you have any further questions or concerns about your rights as a research subject, please contact 
your research doctor or the UCSD Human Research Protections Program at 858-246-HRPP (858-
246-4777).