Clinical trial NCT04935931
Conditions: Eating Disorders Binge Eating Purging (Eating Disorders)
Keywords: Pediatric Adolescent Eating Disorder Neuroimaging Naltrexone
Sponsor: Children's Mercy Hospital Kansas City
Start date: 2021-07-16; Completion date: 2022-06-30
Enrollment: 13 participants; Allocation: NA; Intervention model: SINGLE_GROUP

Brief summary:
The purpose of this open-label, pilot study is to evaluate fMRI as a biomarker of opioid antagonism in adolescents with ED. Modulation of brain activation will be examined in regions of interest by fMRI using a food-specific and general reward task in adolescents with ED in a pre/post design.

Detailed description:
This is an open-label, interventional trial to evaluate reward system modulation (detected by neuroimaging) in response to opioid antagonism (i.e., naltrexone) in adolescents aged 13-21 years with an eating disorder characterized by the target behaviors of binge eating and/or purging (e.g., AN-BP, BN, BED). A pre/post design completed on the same day will be employed to quantify within-individual change while reducing potential confounding due to known neuroimaging variables (e.g., menstrual phase, treatment changes) that may occur with time elapsed between study visits. Self-report data regarding will be captured via electronic surveys using validated instruments (where possible), structured interview, study records.

Reward System Modulation by fMRI. Each scan will last approximately 1 hour and involve two reward activation paradigms: passive food view (PFV) and monetary incentive delay (MID). These two reward activation paradigms provide distinct insight and will generate pilot data to support the choice of the optimal paradigm for further testing of reward system modulation in adolescents with eating disorders. PFV provides a paradigm that is relevant to the target behaviors (i.e., binge eating, purging), has been evaluated in ED patients, in response to naltrexone in adults, and is expected to activate food cue-reactivity regions (e.g., prefrontal cortex). MID is a widely used paradigm in adolescents to detect reward anticipation and receipt particularly in the striatum and is currently being used to study the developmental trajectory of reward processing in the longitudinal Adolescent Brain Cognitive Development (ABCD) trial. To the greatest extent possible, we will harmonize our fMRI parameters with those published for ABCD.

Opioid Antagonism and exposure-response linkage. A single oral dose of naltrexone hydrochloride 50 mg tablet will be administered. Plasma and urine will be obtained to measure systemic exposure to naltrexone and it primary, active metabolite, 6-beta-naltrexol, using a validated UPLC-MS/MS assay.

Arms: arm 1: Pre/post fMRI
Interventions: intervention 1: Naltrexone
Intervention descriptions: intervention 1: naltrexone 50 mg PO x 1

Protocol documents:
Prot_SAP_ICF_000.pdf: 
SHORT TITLE: Naltrexone Neuroimaging  
Page 1 of 16 
 
 
 
PROTOCOL TITLE: 
Eating Disorder Individualized Therapeutics-Naltrexone Neuroimaging 
 
SHORT TITLE: Naltrexone neuroimaging 
 
CLINICALTRIALS.GOV: NCT04935931 
 
PRINCIPAL INVESTIGATOR: 
Stephani Stancil, PhD, APRN 
Divisions of Adolescent Medicine and Clinical Pharmacology 
slstancil@cmh.edu 
816-731-7186  
 
PROTOCOL DATE: 2/2/22 
 
 


SHORT TITLE: Naltrexone Neuroimaging  
Page 2 of 16 
 
 
1.0 
Study Summary 
 
Study Title 
Eating Disorder Individualized Therapeutics-Naltrexone 
Neuroimaging 
Study Design 
Open label, prospective trial 
Primary Objective 
Modulation of reward system measured by fMRI 
Research 
Intervention(s)/ 
Investigational 
Agent(s)  
Naltrexone 50 mg oral tablet x 1 
Study Population 
Adolescents aged 13-21 years 
Sample Size 
Pre-screening up to 1000 individuals, Up to n=50 
Study Duration for 
Individual 
Participants 
1 study visit (~10 hours)  
Study Specific 
Abbreviations/ 
Definitions  
FMRI – functional magnetic brain imaging 
BOLD – blood oxygenation level dependent 
AN – anorexia nervosa 
BN – bulimia nervosa 
BED – binge eating disorder 
ED – eating disorder 
ROI – region of interest 
MID – monetary incentive delay 
PFV – passive food view 
EPSI – eating pathology symptom inventory 
AKR – aldoketoreductase 
OPRM – opioid receptor mu 
NTX - naltrexone 
 
 
2.0 
Objectives 
The overall goal of this project is to generate pilot data to support the development of fMRI as a 
pharmacodynamic biomarker of opioid antagonism in adolescents with ED, which will be accomplished 
through the following specific aims (SA):   
SA1. Define the extent of within individual reward system modulation and identify the brain 
region most responsive to opioid antagonism in adolescents with binge/purge ED. We will use 
fMRI to detect percent blood oxygenation level dependent (%BOLD) changes pre- and post-opioid 
antagonist treatment (i.e., naltrexone) within individuals during a food reward and general reward-
related task using regions of interest (ROI) analysis. We hypothesize that the anterior cingulate cortex 
(ACC) will be most responsive to naltrexone in adolescents with ED during food reward. 
SA2. Determine the fMRI reward paradigm most sensitive to opioid antagonism in adolescents 
with binge/purge ED. Using the method described in SA1, we anticipate that the food paradigm will 
be more sensitive (e.g., higher t-score) in reward ROI to opioid antagonism in our target population.  
SA3. Describe the naltrexone exposure-brain response relationship using fMRI in adolescents 
with binge/purge ED. We will link pharmacokinetic (PK) parameters of exposure with %BOLD change 
in subjects during the reward paradigms using ROI analysis. Based on our preliminary data suggesting 


SHORT TITLE: Naltrexone Neuroimaging  
Page 3 of 16 
 
widely variable maximum plasma concentrations (Cmax) of naltrexone in adolescents with ED (17-fold), 
we hypothesize that reduced Cmax will be associated with reduced activation in reward-related ROIs. 
3.0 
Background 
Naltrexone shows promise in treatment of binge eating and purging. Previous studies have 
demonstrated that naltrexone, a drug that interrupts the opioid reward circuit, reduces binge eating 
and purging in adults (1-3). Our recent retrospective case series revealed that naltrexone reduced 
binge/purge behaviors in approximately 60% of adolescents with no serious side effects (4). However, 
the patient-specific factors associated with response vs. non-response remain to be elucidated.  
Naltrexone systemic exposure is highly variable. Preliminary data from our current naltrexone 
pharmacokinetic study demonstrate significant interindividual variability in the rate and extent to which 
naltrexone is absorbed in adolescents with ED. With systemic exposure varying by 16-fold, 
pharmacokinetic differences may contribute to variability in drug response.  
Biomarkers of brain response are lacking. Opioid receptor binding studies done in adults using 
positron emission tomography (PET) show nearly 100% mu opioid receptor (OPRM) blockade with 
naltrexone 50 mg (5); however, 1 in 3 adolescents with ED fail to respond at this dose (4) and higher 
doses may be necessary to reach therapeutic effect in certain individuals (6, 7). Thus, biomarkers of 
brain response are critically needed to understand the impact of the opioid reward system, and opioid 
antagonism in adolescents with eating disorders.  
Next Steps. Pharmacodynamic biomarkers of brain response are lacking yet are critically needed to 
untangle factors associated with response vs. non-response and advance precision therapeutics. This 
study will initiate the development of a biomarker (i.e., neuroimaging) of opioid antagonism in 
adolescents with eating disorders that will aid in drug development and repurposing. 
4.0 
Study Endpoints 
Outcomes  
Exploratory Outcomes  
Primary: 
• 
RESPONSE (SA1) - defined 
by Δ%BOLD pre/post-ntx in 
ROI 
Secondary:  
▪ 
ROI (SA1) - 
defined by coordinates with 
largest response  
▪ 
OPTIMAL 
PARADIGM (SA2) – paradigm 
(PFV or MID) resulting 
in larger response   
▪ 
EXPOSURE (SA3) – defined 
by ntx Cmax   
▪ 
RESPONSE x OPRM1 genetic variation  
▪ 
RESPONSE x metabolomic profile  
▪ 
RESPONSE x impulsivity  
▪ 
RESPONSE x negative urgency  
▪ 
RESPONSE x delayed discounting  
▪ 
EXPOSURE x AKR1C4 genetic variation  
▪ 
EXPOSURE x metabolomic profile  
 
5.0 
Study Design 
This is an open-label, interventional trial to evaluate reward system modulation (detected by 
neuroimaging) in response to opioid antagonism (i.e., naltrexone) in adolescents aged 13-21 years 
with an eating disorder characterized by the target behaviors of binge eating and/or purging (e.g., AN-


SHORT TITLE: Naltrexone Neuroimaging  
Page 4 of 16 
 
BP, BN, BED). A pre/post design completed on the same day will be employed to quantify within-
individual change while reducing potential confounding due to known neuroimaging variables (e.g., 
menstrual phase, treatment changes) that may occur with time elapsed between study visits.  
Up to 50 individuals may be enrolled to meet our objectives.  
6.0 
Inclusion and Exclusion Criteria 
Inclusion Criteria 
• 
Adolescents aged 13-21 years 
• 
Eating disorder diagnosis per DSM-V criteria that is characterized by binge eating (defined as loss 
of control of eating resulting in large amount of food consumed in a short period of time) and/or 
purging (e.g., vomiting, excessive exercising, laxative use) 
• 
Stable medication regimen (no dose or drug changes in the past 4 weeks) 
• 
Participant and parent/legal guardian (if under 18 years) are willing and able to provide informed 
permission/assent/consent for the study 
 
Exclusion Criteria 
• 
Pregnant (via UCG) 
• 
Prior hypersensitivity reaction to naltrexone (e.g., anaphylaxis) 
• 
Non-removable metal in the body 
• 
Current naltrexone use 
• 
Self-reported opioid use in the past 7 days 
• 
A language barrier (e.g., non-English speaking) for the participant that precludes communication 
and/or ability to complete all study-related requirements. 
 
English speaking participants whose parent/guardian are non-English speaking may be consented 
using a translated PAC form. Participants will have suitable English proficiency to complete study 
questionnaires and logs. Determination of proficiency will be at the discretion of the PI. Non-English 
speaking participants are excluded because the validated questionnaires used in this study to 
measure eating disorder symptomatology (EPSI) is not yet available in languages other than English. 
This assessment was chosen because of the ability to discriminate eating disorder behaviors and 
validation in the target age range. It is also the main assessment used in the CM Eating Disorder 
Center and thus parallels clinical practice.  
 
Non-English Speaking Subjects: 
• 
Parent/guardians only 
• 
language(s) other than English understood by prospective parent/guardians: Spanish  
• 
ORI Translation Program to translate the PAC form 
7.0 
Prescreening 
Prescreening will occur through discussion with treating clinicians and review of medical records 
(through automated EHR report for those with eating disorder diagnoses). We anticipate that ~5% of 
those pre-screening will enroll, thus we estimate pre-screening up to 1000 individuals.   
8.0 
Recruitment 
Recruitment will occur throughout the region using various means of IRB approved media to 
achieve target enrollment, including the following:  


SHORT TITLE: Naltrexone Neuroimaging  
Page 5 of 16 
 
• 
Social media 
• 
Potential participants may learn about this study from information posted on the 
internal Children’s Mercy Hospital website and on the Children’s Mercy Research 
Institute (CMRI) public facing website. Social media platforms, such as Twitter and 
Facebook, may be used to disseminate study information. The social media 
platforms will reference or link to study information available on the CMRI website. 
Use of social media to share study information will be compliant with any existing 
CMH policies. The use of social media to share study information will not begin until 
these policies have been developed. Presentation of study information and content 
posted on the CMRI website will be at the discretion of the Digital Team, Research 
Administration, and the research team. Modification of images may be applied by 
the Digital Team and Research Administration to in be consistent with the aesthetic 
of the CMRI webpage. All study information will be approved by the IRB. 
• 
Flyers 
• 
Email blasts (e.g., Daily E-news) 
• 
Direct communication from study staff to potential participants (identified by pre-
screening) via available contact information.  
• 
Self-referral: Individuals who express interest may contact study staff or click the link 
provided on recruitment materials. If the potential participant would like to receive more 
information regarding the study, they can also complete a contact form so a team member may 
contact the individual.  
• 
Provider referral: Potential participants may be referred to the study team by their health 
care provider. The provider may share the potential participant’s contact information if they 
obtain permission to do so.    
A member of the research team may call or email potential participant up to three times using 
CHM email, Microsoft Teams or CMH phones. When contacted, individuals will undergo a brief 
screen to determine potential eligibility. Interested individuals will then schedule a time (virtually 
or in person) to fully explain the study, answer questions and obtain informed consent. This 
may occur at initial contact based on participant preference. 
9.0 
Study Procedures 
The study will involve a screening encounter and one study day.   
Study Visit Element  
Main Procedures/Data Collected 
Approximate Clock 
Time  
Screening and Consent  
Inclusion/exclusion criteria, Consent 
In person, telephone or 
e-consent prior to study 
visit 
I/E confirmation and medical 
History 
Inclusion/exclusion criteria review and 
confirmation, medical history, anthropometrics, 
pregnancy test (if applicable)   
7 am  
Meal #1 (1 hour before scan 
#1)  
Standardized CHO:PRO:FAT content  
8 am  
Baseline/pre-dose measures  
Impulsiveness (BIS-brief), negative urgency 
(UPPS-P subscale); delayed discounting, blood 
draw (targeted metabolomic panel, genetic 
analysis)  
8:20 am  
fMRI scan #1  
Hunger rating, reward related tasks (PFV, MID)  
9 am  
Naltrexone (NTX) dosing  
Naltrexone 50 mg PO 2 hours prior to scan #2  
10:30 am  
Meal #2 (1 hour before 
scan #2)  
Standardized CHO:PRO:FAT content  
11:30 pm  


SHORT TITLE: Naltrexone Neuroimaging  
Page 6 of 16 
 
fMRI scan #2 (2 hours post-
NTX)  
Hunger rating, reward related tasks (PFV, MID)  
12:30 pm  
Pharmacokinetic analysis  
3 mL blood samples - pre-dose, 0.5, 1, 1.5, 2, 3, 4, 
6, 7 hours post-naltrexone dose.  
5:30 pm   
(last PK draw & study 
end)  
 
Screening and consent. The study will be reviewed in depth with the participant and his/her 
parents/legal guardian when applicable.  They will be provided sufficient time to review the PAC form, have all 
questions answered, and concerns addressed. If they agree to participate, they will sign the PAC form. This 
may occur in person, over the phone (using telephone script) or via e-consent. In the event the 
parent/guardian is non-English speaking, interpreter will be offered along with provision of translated PAC 
form. The participant must have English proficiency to complete study procedures (see inclusion criteria).  
Screening failures (i.e., participants meeting any exclusion criteria) may be screened again at a future 
time point at the discretion of the Principal Investigator.   
Pre-visit Planning. Scheduled participants may be contacted ahead of study with a reminder of their 
study appointment. Once PAC has been obtained, participants will be reminded to avoid food for 4 hours prior 
to study day.  
Assessments (including categories of data collected). Self-report data will be captured via 
electronic surveys (e.g., Research Electronic Data Capture -REDCap), structured interview, study 
records. Anthropometrics. Height, blind weight will be obtained; body mass index (BMI), BMI z-score, % ideal 
body weight will be calculated. Structured interview. Study staff will obtain participant 
demographics, ED, medical, family & menstrual history. Confidential social history will be obtained via self-
report electronic survey. Laboratory. Urine drug panel will objectively assess illicit substance use (e.g., 
nicotine, THC) at baseline along with urine pH and specific gravity and used as covariates in analysis. Eating 
Disorder Symptom Burden. The EPSI will evaluate symptom burden at baseline. The EPSI has excellent 
validity and reliability derived from a diverse population, has published normative data(8, 9) and includes 
various sub-scales (e.g., body dissatisfaction, cognitive restraint) that will allow characterization of our 
sample. Hunger. Before each scan, hunger will be assessed. Safety. Baseline heart rate and blood pressure 
will be recorded. Physical symptoms that may occur after naltrexone administration will be assessed.  
Reward System Modulation by fMRI. Each participant will undergo two fMRI scans on the same day. 
Scan #1 (pre) will be in the fed state before naltrexone administration. Scan #2 (post) will be in the fed state 2 
hours after naltrexone. Each scan will last approximately 1 hour and involve two reward activation 
paradigms(10-12): passive food view (PFV) and monetary incentive delay (MID). These two reward activation 
paradigms provide distinct insight and will generate pilot data to support the choice of the optimal paradigm 
for further testing of reward system modulation in adolescents with eating disorders. PFV provides a paradigm 
that is relevant to the target behaviors (i.e., binge eating, purging), has been evaluated in ED patients, 
in response to naltrexone in adults, and is expected to activate food cue-reactivity regions (e.g., prefrontal 
cortex). MID is a widely used paradigm in adolescents to detect reward anticipation and receipt particularly in 
the striatum and is currently being used to study the developmental trajectory of reward processing in 
the longitudinal Adolescent Brain Cognitive Development (ABCD) trial. To the greatest extent possible, we 
will harmonize our fMRI parameters with those published for ABCD.   
Opioid Antagonism. A single oral dose of naltrexone hydrochloride 50 mg tablet will be administered 
by licensed study staff 2 hr (±1 hr) before scan #2.  Complete opioid receptor blockade is evident at 1-
hour post-dose, which overlaps with time at maximum concentration in plasma (Tmax) and persists for at 
least 24 hours post-dose in adults(13, 14). In our PK study in adolescents with ED, preliminary analysis 
shows Tmax at 2 hour. Thus, optimal timing of 2 hours was conservatively chosen while providing a feasibility 
window supported by evidence. Naltrexone is well-tolerated and difficult to distinguish from placebo in blinded 
trials(15-17).  CM IDS pharmacy will dispense study medication. Naltrexone hydrochloride 50 mg tablet is 
FDA approved for opioid and alcohol use disorder and used off-label for the treatment of compulsive and 
impulsive behaviors in children, adolescents and adults. Examples of compulsive and impulsive pertinent to 
this study include binge eating and purging (e.g., vomiting). Evidence for safe and efficacious use of 
naltrexone for these behaviors is available (4). This study does not significantly increase the risk associated 
with naltrexone as the commercially available dose, formulation and route chosen is consistent with current 
clinical practice at doses ranging from 50 -200 mg/day. Additionally, a meta-analysis revealed that naltrexone, 


SHORT TITLE: Naltrexone Neuroimaging  
Page 7 of 16 
 
when compared with placebo, is not associated with serious adverse events(17). It is not the intent of this 
study to generate data for submission to the FDA or to support a significant change in advertising of the drug. 
Storage, control and dispensation of the drug will occur through collaboration with IDS pharmacy. Use of 
naltrexone for this study meets criteria for IND exemption, category #1 (21 CFR 312.2(b)(1)).  
Meals. Imaging will occur in the fed state using a standardized meal to avoid prolonged fasting that 
may compromise the health and recovery of the target population.  This is not expected to meaningfully 
interfere with the detection of reward system modulation within individuals. Previous fMRI studies in 
adults suggest that individuals with disordered eating and/or obesity/overweight may exhibit stronger reward 
activation in the fed state compared with healthy controls(18, 19). Healthy weight individuals still exhibit strong 
reward activation, particularly in the ACC, in the fed versus fasted state, even though small reductions are 
seen(20).  
Systemic Drug Exposure-Response Linkage. Plasma and urine will be obtained to measure 
systemic exposure to naltrexone and it primary, active metabolite, 6-beta-naltrexol, using a validated UPLC-
MS/MS assay. Blood samples (3 mL) will be obtained from a peripheral intravenous catheter (PIV) to 
minimize discomfort associated with repeated blood draws (Table 1). Genomic Variation. To understand the 
impact of genetic variation on the naltrexone exposure-response relationship, DNA will be extracted from 
whole blood and genotyped for variants of interest.  
Exploratory Assessments. We understand that the most clinically practical intervention will involve 
peripheral evaluation. The following exploration gets us closer to finding surrogate markers. Metabolomic 
Variation. To explore the correlation between peripheral and central (fMRI) biomarkers, targeted metabolomic 
panel will be completed on plasma at baseline (pre-dose) and post-dose. Impulsivity. To explore the 
correlation between impulsivity and reward system modulation by naltrexone, this trait may be measured by 
the self-report Barratt Impulsiveness Scale-brief - BIS-brief)(21) and behavioral task (go/no go)(22). Negative 
urgency. Negative urgency, the propensity to be impulsive when upset, is associated with bulimic 
symptoms in adolescents and adults(23, 24). To explore the relationship between negative urgency and 
reward system modulation by naltrexone, the self-report UPPS-P subscale may be employed(25, 
26). Delayed discounting. Delayed discounting rates are increased in adolescents with impulsivity, altered 
executive function and substance use(27) and adults with BED or AN-BP(28) . To explore the relationship 
between delayed discounting rates and within individual reward system modulation by opioid antagonism, 
participants in our study may complete delayed discounting task at baseline.   
Optional EEG. Up to 50 participants may be offered the opportunity to complete an EEG. This will be 
offered to those who meet I/E criteria stated above and at the discretion of the PI based on available 
resources (e.g., access to equipment and trained staff at Hoglund during study day). If offered, the participant 
may decline this and still complete the remaining study procedures. 
Total blood sampling. No more than 8 teaspoons (40 ml) of blood will be obtained during the study 
visit (9 PK time points, 1 genomic sample, 2 metabolomic samples, each 3 ml).   
Compensation. Participants will be given $400 via greenphire or CM preferred mechanism for 
completion of Study Day 1.  
Biosafety Information. This study will involve handling, processing and transporting human 
biosamples from Hoglund to CMRI Clinical Pharmacology labs. Biosafety regulations will be followed. 
10.0 Risks to Subjects and Mitigation Strategies 
• 
Small risk of loss of confidentiality, but every effort will be made to prevent this and keep participant 
information confidential. If the participant/LAR wish provides an email address and/or phone 
number, the study team may communicate with them and they will be informed that this is not a 
secure method and could be accessed by someone else in the event of a security breach. The 
hospital is not liable for security breaches.  
• 
Minimal discomfort or bruising may occur with drawing blood and IV placement. The participant may 
be given the option of a numbing agent to help ease the pain of needle sticks. 
• 
When answering the brief questionnaires, the questions asked may be uncomfortable or 
embarrassing. These risks are minimum and unlikely to occur. The participant does not have to give 
any information they do not want to give. Confidentiality will be protected to the greatest extent 
possible and answers will not be released to the care team.  


SHORT TITLE: Naltrexone Neuroimaging  
Page 8 of 16 
 
• 
Side effects to naltrexone occur in ~10% of patients, are typically mild and go away on their own 
(e.g., nausea) and do not differ from those receiving a placebo (e.g., sugar pill). Allergic reaction to 
naltrexone is rare and usually happens right away after taking the medicine. Symptoms include 
hives and difficulty breathing. Medications for immediate treatment of severe allergic reactions and 
trained personnel will be available in the clinic where the study drug is given.  
• 
Genetic testing carries the possibility of discrimination. However, a Federal law called the Genetic 
Information Nondiscrimination Act (GINA) generally makes it illegal for health insurance companies, 
group health plans, and most employers to discriminate based on genetic information. Additionally, 
results will be kept in the study record and not released to your medical record.  
• 
Incidental finding from the neuroimaging (e.g., fMRI) may occur. Whenever brain imaging is done, 
there is a chance of finding something unexpected and unrelated to the research study that may 
have some clinical implications. The neuroimaging used in this study is for research purposes only 
and is not the same as clinical neuroimaging.   
11.0 Potential Benefits 
Participants have the possibility of direct benefit should they experience eating disorder symptom 
reduction after taking naltrexone (e.g. reduced urge to binge and/or purge or lack of positive 
reinforcement from binge/purge). It is plausible to experience an effect after a one-time dose based on 
evidence of complete opioid antagonism as soon as 2 hours after a one-time dose(13, 14). Should 
individuals experience a benefit, they may choose to share this information with their treating clinician 
and consider initiating ongoing therapy with naltrexone. Sharing such information with the treating 
clinician is outside the scope of this study and would solely be at the discretion of the participant.  
The knowledge gained from this study has the potential to further our understanding of alterations in 
the reward pathway and their contribution to eating disorder and benefit society through advancement 
of mental health knowledge and treatment.  
12.0 Investigator Assessment of Risk/Benefits Ratio:  
Select as 
applicable: 
Pediatric Risk Category: 
☐ 
Category 
1  
Research not involving greater than minimal risk  
(45 CFR §46.404 and 21 CFR §50.51)   
☒ 
Category 
2 
Research involving greater than minimal risk 
but presenting the prospect of direct benefit 
to the individual subjects. (45 CFR §46.405 
and 21 CFR §50.52) 
☐ 
Category 
3 
Research involving greater than minimal risk and 
no prospect of direct benefit to individual 
subjects, but 
likely to yield generalizable knowledge about the 
subject's disorder or condition.  
(45 CFR §46.406 and 21 CFR §50.53) 
☐ 
Category 
4 
Research not otherwise approvable which 
presents an opportunity to understand, prevent, 
or alleviate a 
serious problem affecting the health or welfare of 
children. (45 CFR §46.407 and 21 CFR §50.54) 
Select if 
applicable: 
Adult Risk Category: 
☐ 
Not Greater than Minimal Risk 
☒ 
Greater than Minimal Risk 


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Page 9 of 16 
 
 
13.0 Payment, Reimbursement and Tangible Property provided to subjects  
Payment to Subjects: Greenphire or CM approved equivalent will be used to provide payment 
of $400 to each participant at the conclusion of the study day as renumeration for their time.  
Tangible Property:  N/A 
14.0 Compensation for Research-Related Injury 
No compensation for research-related injury will occur. Should a serious adverse event occur 
during the study day, the participant will be taken to the nearest emergency department or the 
emergency department of their choice (e.g., Children’s Mercy or KUMED). 
15.0 Economic Burden to Subjects 
Participants will not be responsible for the cost of any study procedure. 
16.0 Permission/Assent/Consent Process and HIPAA authorization 
Full written permission and assent and HIPAA authorization will be obtained for pediatric participants 
and consent for adult/emancipated participants. The study will be explained, and participants/LAR will 
be given as much time as they need to review PAC, ask questions and come to a decision. This may 
occur over the phone, virtually (e.g, CM approved platform like Teams) or in person based on 
participant preference and available resources to the study team. PAC will be signed by hand or 
electronically. 
The study is requesting the option of using a telephone/telemedicine consent process for initial 
consenting.  CM telephone/telemedicine consent process research policy will be followed. 
 
A waiver of written documentation of consent and alteration of HIPAA authorization (p/a/c form 
provided but signature will NOT be obtained, e.g. verbal consent) is requested for participants who will 
re-consent at age 18 per CMRI policy. Patients who were <18 at initial enrollment, but turn 18 after 
study procedure completion will have signed parental consent/participant assent (confirmed by study 
staff) and completed all study procedures, but may have PHI stored in the study DCF while the study 
remains open which represents no more than minimal risk to the participant (and involves no 
procedures for which written consent is normally required outside of the research context). PHI will not 
be reused or disclosed to anyone not involved in this research.  The research cannot practicably be 
conducted without the Alteration of HIPAA authorization as many of the patients who turn 18 after 
study procedure completion may already be treated and discharged.  Data from all these participants 
is needed to describe aims of the study.  These participants will be identified by review of study 
participant DCFs. If verbal re-consent cannot be accomplished via telephone/telemedicine, de-
identification of study samples and data will occur.  
 
A partial waiver of HIPAA authorization is requested for pre-screening/recruitment. A report will be 
generated from HIM that includes PHI of potential participants (e.g., name, MR, diagnosis code). Use 
of PHI is no more than minimal risk to the privacy of the individuals because PHI will be kept on CM 
protected network, accessed by study team and destroyed with other study documents. This will allow 
for the description of recruitment efforts in aggregate form (e.g., number of patients enrolled/number of 
patients eligible). This PHI will not be reused or disclosed to anyone or entity outside of the study 
team. Without this waiver, recruitment would not be feasible as we would fail to identify potential study 
participants. Relying solely on provider or patient self-referral for study participation would compromise 
the ability to complete the study given the relatively small patient pool of which to recruit from. In 
addition, these individuals may be screened for inclusion/exclusion criteria to avoid unnecessary 


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contact if patient does not meet criteria. This approach has been successful in recruiting for an IRB-
approved study in adolescents with eating disorders. 
 
17.0 Identifiable Information 
1. Name/Initials 
☐ Accessed only 
☒ Recorded 
2. All elements of date (except year) directly 
related to an individual (e.g. date of birth, 
admission date, discharge date, date of 
death) 
☐ Accessed only 
☒ Recorded 
3. Medical record number 
☐ Accessed only 
☒ Recorded 
4. Account number 
☐ Accessed only 
☒ Recorded 
5. Health plan identification number 
☐ Accessed only 
☐ Recorded 
6. Social Security Number 
☐ Accessed only 
☒ Recorded 
(only if needed, 
see above) 
7. Device identifiers and serial number 
☐ Accessed only 
☐ Recorded 
8. Certificate/License number 
☐ Accessed only 
☐ Recorded 
9. Telephone number 
☐ Accessed only 
☒ Recorded 
10. Fax number 
☐ Accessed only 
☐ Recorded 
11. Email addresses 
☐ Accessed only 
☒ Recorded 
12. Web addresses (URLs); Internet IP 
addresses 
☐ Accessed only 
☐ Recorded 
13. Street address, city, county, precinct, zip 
code or equivalent geographical codes 
☐ Accessed only 
☒ Recorded 
14. Full face photographic images and any 
comparable images 
☒ Accessed only 
☐ Recorded 
15. Biometric identifiers, including finger and 
voice print 
☐ Accessed only 
☐ Recorded 
16. Vehicle identifiers and serial numbers, 
including license plate number 
☐ Accessed only 
☐ Recorded 
17. Any other unique identifying number, 
characteristic or code that may help identify 
individual participants including their initials 
(e.g. student or employee ID number) 
☐ Accessed only 
☐ Recorded 
18. Elements of date, including year, for persons 
90 years or older 
☐ Accessed only 
☐ Recorded 
19. Other: 
☐ Accessed only 
☐ Recorded 
 
18.0 Genetic Analysis Information 
Single nucleotide polymorphism (SNPs) analysis and genomic sequencing may occur as part of this 
study for research purposes only to explore the impact of genetic variation on pharmacokinetics, 
pharmacodynamics and/or disease. Genetic information may be stored in the Adolescent Medicine 
Pharmacogenomic Repository (AMP) (IRB#13020033).  


SHORT TITLE: Naltrexone Neuroimaging  
Page 11 of 16 
 
19.0 Sharing of Results with Subjects 
Results (including genetic analysis or any incidental findings on neuroimaging) will not be shared 
individually with participants. It is the intent of study to publish study results and thus participants may 
learn about study results in such publications.  
20.0 Storage/Banking of Data and Specimens for Future Research 
Data and leftover specimens will be stored in the existing Adolescent Medicine Pharmacogenomic 
Repository (AMP), IRB#13020033 which describes the potential for sharing of deidentified samples 
with other researchers per IRB protocol.  
 
21.0 Withdrawal of Subjects 
Participants may withdrawal at any time during the study. To withdrawal participants will notify the 
study team in writing that they wish to withdrawal. Study procedures will cease. Any data collected will 
be retained for potential analysis.  
 
22.0 Data Analysis:  
Outcome analyses. Outcomes are defined per Table 2. SA1. Response. fMRI data will be analyzed in 
AFNI in two ways: 1) region of interest (ROI) analysis in a priori reward ROIs including the 
ventromedial prefrontal cortex, ACC and striatum and 2) exploratory whole brain analysis to identify 
regions outside the reward network that may also respond to naltrexone (e.g., insula, dorsolateral 
prefrontal cortex, dorsal ACC). We have chosen to use a pre-defined ROI analysis which will be 
selected from a meta-analysis of passive viewing food tasks and MID studies using neurosynth.org or 
similar(29). Although ROI approaches do present challenges in fMRI analyses, this hypothesis-driven 
approach has been chosen to focus the primary analysis to test targeted reward related changes 
associated with treatment. Exploratory analysis described below will use advanced fMRI analysis 
approaches to take advantage of the richness of the whole-brain data. SA2. Optimal paradigm. The 
%BOLD changes will be compared between paradigms by LMM using paradigm (PFV, MID) and time 
(pre, post) as fixed-effects, and random individual and/or paradigm intercepts. SA3. The changes in 
%BOLD and changes in Exposure (log-scale) will be correlated by Pearson’s correlation coefficient; 
the 95% CI will be estimated by non-parametric bootstrap using the bias-corrected and accelerated 
method.  
PKPD analysis. Kinetica 5.0 or similar software will be used to model PK parameters (e.g., Cmax, 
AUC0-inf).  
 
23.0 Adverse Events and Unanticipated Problems 
Any adverse event that occurs during study participation will be recorded. The primary safety end point 
will be based on frequency of AEs during the Study Day. 
 
Definition and Grading Intensity of Adverse Events 
An adverse event is defined as any undesired change in the body structure (signs) or body function 
(symptoms), whether or not considered drug-related. For the purposes of this study, drug-related is 
independent from study-related, as described above.  During the entire duration of the study, subjects 
will be instructed to report all adverse events. All adverse events, whether volunteered, elicited, or noted 
on physical examination, will be recorded throughout the study. Each adverse event will be described 
by 1) its duration 2) severity grade (see below for definition), 3) its relationship to the medication studied 
(none, possible, probable, definite) 4) the action(s) taken. 
 
The severity of adverse events will be categorized as follows: 


SHORT TITLE: Naltrexone Neuroimaging  
Page 12 of 16 
 
• 
MILD = Experience is minor and does not cause significant discomfort to subject or change in 
activities of daily living (ADL); subject is aware of symptoms but symptoms are easily tolerated.  
• 
MODERATE = Experience is an inconvenience or concern to the subject and causes 
interference with ADL but the subject is able to continue with ADL.  
• 
SEVERE = Experience significantly interferes with ADL and the subject is incapacitated and/or 
unable to continue with ADL. 
Serious Adverse Event (SAE) Reporting 
A serious adverse drug experience (by FDA definition) is any adverse test material event occurring at 
any dose that results in any of the following outcomes: 
• 
Death 
• 
Life-threatening adverse experience 
• 
Inpatient hospitalization or prolongation of existing hospitalization 
• 
Persistent or significant disability/incapacity 
• 
Congenital anomaly/birth defect 
Any serious adverse event will be reported verbally to the primary investigator (see contact info below) 
and naltrexone prescriber within 24 hours of notification. Written notification will be sent to the IRB within 
3 working days.  
Stephani Stancil, PhD, APRN 816-309-4951, slstancil@cmh.edu 
NOTE:  The term “severe” is often used to describe the intensity (severity) of a specific event (as in mild, 
moderate, or severe myocardial infarction); the event itself, however, may be of relatively minor medical 
significance (such as a severe headache). This is not the same as “serious,” which is based on 
participant/event outcome or action criteria usually associated with events that pose a threat to the 
participant’s life or functioning. Seriousness (not intensity) serves as a guide for defining regulatory 
reporting obligations. 
24.0 Provisions to Monitor the Data to Ensure the Safety of Subjects 
A data safety/monitoring committee will be established to monitor the safety of the study and 
include the PI, senior mentor(s), and a medical  
provider not part of the study. Cumulative and new safety data will be reviewed at least every 6 
months or sooner if serious adverse event occurs.  
 
Data reviewed will include any adverse event occurring during the study day or reported by 
participant to have occurred after the study, but thought to be associated with the study (via 
participant initiated communication).  
25.0 Data Management 
Data will be collected and recorded during the study by members of the study team. Categories of 
data collected as listed in section 9.0 The investigator and members of the research team are bound 
to keep this information confidential and will do everything within their power to avoid loss of 
confidentiality. The documents will be stored on the hospital’s secure system (e.g., OneDrive) with 
access restricted to members of the study team.   
 
The investigator agrees to adhere to the document retention procedures and retain essential documents 
for 3 years after the completion or discontinuation of the trial.  Essential documents include: 
1. 
IRB approvals for the study protocol and all amendments 
2. 
DCF 
3. 
subjects' signed PAC forms 
4. 
any other pertinent study documents 


SHORT TITLE: Naltrexone Neuroimaging  
Page 13 of 16 
 
26.0 Multi-site Research 
Study procedures and imaging data analysis will occur at Hoglund Biomedical Imaging Center, part of 
the CTSA located on the campus of University of Kansas Medical Center. Additional sample 
processing and data analysis will occur at Children’s Mercy Kansas City.  
 
CM will be the IRB of record with a request for KUMC to rely on CM.  
27.0 Equitable Selection and Vulnerable Populations 
Age range was chosen based on relevance to the population of interest (e.g., adolescents with 
eating disorders) and alignment with validated eating disorder symptom burden questionnaire 
(EPSI).  
Vulnerable Populations: 
☐ Children/Minors (under 7 years of age) 
☒ Children/Minors (7-17 years of age) 
☐ Neonates (infants less than 30 days old) 
☐ Neonates of Uncertain Viability (infants 
less than 30 days old) 
☐ Non-Viable Neonates (infants less than 
30 days old) 
☐ Wards of the State 
☐ Fetuses 
☐ Pregnant Women  
☐ Adults with impaired decision-making 
capacity         
☒ CM Employees 
☒ CM Students/Residents/ Fellows 
(categorized as “trainees”) 
☐ Economically or Educationally 
Disadvantaged Persons 
☐ Prisoners 
 
 
For CM employees or trainees, the risk of coercion will be minimized by ensuring that they 
will not be recruited or enrolled by their direct supervisor and through reassurance that their 
decision regarding participation does not impact their employment or educational status at 
CM. 
 


SHORT TITLE: Naltrexone Neuroimaging 
Page 14 of 16 
 
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Mitchell JE, Christenson G, Jennings J, Huber M, Thomas B, Pomeroy C, 
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1988/05/01. PubMed PMID: 2841709. 
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Raingeard I, Courtet P, Renard E, Bringer J. Naltrexone improves blood glucose 
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Forbush KT, Wildes JE, Hunt TK. Gender norms, psychometric properties, and 
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9. 
Forbush KT, Wildes JE, Pollack LO, Dunbar D, Luo J, Patterson K, Petruzzi L, 
Pollpeter M, Miller H, Stone A, Bright A, Watson D. Development and validation of the 
Eating Pathology Symptoms Inventory (EPSI). Psychol Assess. 2013;25(3):859-78. 
Epub 2013/07/03. doi: 10.1037/a0032639. PubMed PMID: 23815116. 
10. 
Black WR, Lepping RJ, Bruce AS, Powell JN, Bruce JM, Martin LE, Davis AM, 
Brooks WM, Savage CR, Simmons WK. Tonic hyper-connectivity of reward 
neurocircuitry in obese children. Obesity (Silver Spring, Md). 2014;22(7):1590-3. Epub 
2014/03/19. doi: 10.1002/oby.20741. PubMed PMID: 24634397; PMCID: PMC4077951. 
11. 
Bruce AS, Holsen LM, Chambers RJ, Martin LE, Brooks WM, Zarcone JR, 
Butler MG, Savage CR. Obese children show hyperactivation to food pictures in brain 
networks linked to motivation, reward and cognitive control. International journal of 
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PubMed PMID: 20440296; PMCID: PMC6800141. 
12. 
Bruce AS, Lepping RJ, Bruce JM, Cherry JB, Martin LE, Davis AM, Brooks WM, 
Savage CR. Brain responses to food logos in obese and healthy weight children. The 
Journal of pediatrics. 2013;162(4):759-64.e2. Epub 2012/12/06. doi: 
10.1016/j.jpeds.2012.10.003. PubMed PMID: 23211928. 
13. 
Lee MC, Wagner HN, Jr., Tanada S, Frost JJ, Bice AN, Dannals RF. Duration of 
occupancy of opiate receptors by naltrexone. Journal of nuclear medicine : official 


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publication, Society of Nuclear Medicine. 1988;29(7):1207-11. Epub 1988/07/01. 
PubMed PMID: 2839637. 
14. 
Schuh KJ, Walsh SL, Stitzer ML. Onset, magnitude and duration of opioid 
blockade produced by buprenorphine and naltrexone in humans. Psychopharmacology 
(Berl). 1999;145(2):162-74. Epub 1999/08/27. doi: 10.1007/s002130051045. PubMed 
PMID: 10463317. 
15. 
Inagaki TK, Hazlett LI, Andreescu C. Naltrexone alters responses to social and 
physical warmth: implications for social bonding. Social cognitive and affective 
neuroscience. 2019;14(5):471-9. Epub 2019/04/13. doi: 10.1093/scan/nsz026. PubMed 
PMID: 30976797; PMCID: PMC6545530. 
16. 
Tchalova K, MacDonald G. Opioid receptor blockade inhibits self-disclosure 
during a closeness-building social interaction. Psychoneuroendocrinology. 
2020;113:104559. Epub 2020/01/09. doi: 10.1016/j.psyneuen.2019.104559. PubMed 
PMID: 31911348. 
17. 
Bolton M, Hodkinson A, Boda S, Mould A, Panagioti M, Rhodes S, Riste L, van 
Marwijk H. Serious adverse events reported in placebo randomised controlled trials of 
oral naltrexone: a systematic review and meta-analysis. BMC medicine. 2019;17(1):10. 
Epub 2019/01/16. doi: 10.1186/s12916-018-1242-0. PubMed PMID: 30642329; PMCID: 
PMC6332608. 
18. 
Pursey KM, Stanwell P, Callister RJ, Brain K, Collins CE, Burrows TL. Neural 
responses to visual food cues according to weight status: a systematic review of 
functional magnetic resonance imaging studies. Frontiers in nutrition. 2014;1:7. Epub 
2014/01/01. doi: 10.3389/fnut.2014.00007. PubMed PMID: 25988110; PMCID: 
PMC4428493. 
19. 
Pursey KM, Contreras-Rodriguez O, Collins CE, Stanwell P, Burrows TL. Food 
Addiction Symptoms and Amygdala Response in Fasted and Fed States. Nutrients. 
2019;11(6). Epub 2019/06/09. doi: 10.3390/nu11061285. PubMed PMID: 31174338; 
PMCID: PMC6628069. 
20. 
Born JM, Lemmens SG, Rutters F, Nieuwenhuizen AG, Formisano E, Goebel R, 
Westerterp-Plantenga MS. Acute stress and food-related reward activation in the brain 
during food choice during eating in the absence of hunger. International journal of 
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PubMed PMID: 19844211. 
21. 
Steinberg L, Sharp C, Stanford MS, Tharp AT. New tricks for an old measure: 
the development of the Barratt Impulsiveness Scale-Brief (BIS-Brief). Psychol Assess. 
2013;25(1):216-26. Epub 2012/11/15. doi: 10.1037/a0030550. PubMed PMID: 
23148649. 
22. 
Fillmore MT. Drug abuse as a problem of impaired control: current approaches 
and findings. Behavioral and cognitive neuroscience reviews. 2003;2(3):179-97. Epub 
2004/03/10. doi: 10.1177/1534582303257007. PubMed PMID: 15006292. 
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Racine SE, VanHuysse JL, Keel PK, Burt SA, Neale MC, Boker S, Klump KL. 
Eating disorder-specific risk factors moderate the relationship between negative 
urgency and binge eating: A behavioral genetic investigation. J Abnorm Psychol. 
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28691840; PMCID: PMC5505277. 
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Culbert KM, Lavender JM, Crosby RD, Wonderlich SA, Engel SG, Peterson CB, 
Mitchell JE, Crow SJ, Le Grange D, Cao L, Fischer S. Associations between negative 
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of negative urgency. Compr Psychiatry. 2016;66:104-12. Epub 2016/03/21. doi: 
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25. 
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The UPPS-P: Assessing five personality pathways to impulsive behavior2006;10. 
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Whiteside SP, Lynam DR. The Five Factor Model and impulsivity: using a 
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Olson EA, Hooper CJ, Collins P, Luciana M. Adolescents' performance on delay 
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Steward T, Mestre-Bach G, Vintró-Alcaraz C, Agüera Z, Jiménez-Murcia S, 
Granero R, Fernández-Aranda F. Delay Discounting of Reward and Impulsivity in 
Eating Disorders: From Anorexia Nervosa to Binge Eating Disorder. Eur Eat Disord 
Rev. 2017;25(6):601-6. Epub 2017/10/24. doi: 10.1002/erv.2543. PubMed PMID: 
29057603. 
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Yarkoni T, Poldrack RA, Nichols TE, Van Essen DC, Wager TD. Large-scale 
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21706013; PMCID: PMC3146590. 
 
 
 


 Naltrexone Neuroimaging
IRB # 00001668
Page 1 of 6
PERMISSION/ASSENT/CONSENT TO PARTICIPATE IN A 
RESEARCH STUDY AT CHILDREN’S MERCY HOSPITALS
VERSION 10.20.2020 
Eating Disorder Individualized Therapeutics-Naltrexone Neuroimaging (EDIT-N2)
SUMMARY
We are asking you or your child to be in this research study. Being in a research study is completely voluntary, and your 
choice will not affect you or your child’s regular medical care at Children’s Mercy. This research study is done to improve 
our understanding of the medical treatment of adolescents with eating disorders and help us understand why certain 
patients respond to a certain medication, naltrexone, and others don’t. The following things are part of this study: fMRI 
(brain scan), blood draws, medical chart review, questionnaires, a brief computer game. Being in this study involves 1 
study visit lasting approximately 10 hours. The biggest risks from being in this study are adverse reaction to naltrexone 
(rare), discomfort from blood draw and loss of confidentiality. There is the potential for direct benefit of being in this 
study if you or your child experience reduction in eating disorder symptoms (e.g., urge to binge or purge) after taking 
naltrexone. Instead of being in this study, you or your child can choose not to be in the study.
Study Visit
Main Procedures 
Approx. Duration Payment
Screening 
(can occur on the phone or 
combined with study day, 
depending on scheduling)
Consent, Inclusion/Exclusion Criteria
30 min
Study Day
Clear liquids only for 4 hours prior to scheduled 
start time. 
Medical history, Pregnancy test (if applicable), 
Vital signs & measurements (BP, pulse, ht, blind 
wt), Peripheral IV for blood sampling, Urine 
Collection, Dose of naltrexone, Brain scan 
(fMRI) to measure reward response while 
playing a game (choosing money rewards) and 
viewing pictures of foods and non-foods, 
Questionnaires (~30 min)
10 hours 
$400
WHO IS DOING THIS STUDY?
A study team led by Stephani Stancil, PhD, APRN is doing this study. Other health care professionals and researchers 
may help. The study team will not receive any direct personal financial benefits as a result of your decision. 
We are asking you or your child to be a part of this research study. Please read the information below and ask questions 
about anything that you do not understand before you make a choice.
WHY IS THIS STUDY BEING DONE? 
We are looking to improve the treatment of adolescents with eating disorders. Naltrexone is one medication used to treat 
eating disorders, but not everybody responds the same way. We do not know yet why certain people respond, but others 
don’t. This study will look at brain activity and will also collect and store samples and information from adolescents and 
young adults. The samples and information we collect will be used for research now and in the future to improve the care 
of eating disorders.
Naltrexone has been approved by the FDA to treat substance use in adults, but is not yet approved in children and thus has 
not been fully tested in children. Nearly 80% of medications used in children are only approved in adults. Studies in adults 
and children have shown that naltrexone is not associated with serious adverse events at the dose used in this study. 
IRB Effective Date: 6/1/2021


 Naltrexone Neuroimaging
IRB # 00001668
Page 2 of 6
WHO CAN BE IN THIS STUDY?
We are asking you or your child to be a part of this research study because you or your child have been diagnosed with an 
eating disorder that causes binge eating or purging (for example, vomiting or excessive exercise). About 50 patients aged 
13 to 21 years old will be asked to be in this study. 
WHAT WILL HAPPEN TO ME IN THIS STUDY?
If you decide to be in this study, the following things will happen:

We will ask you/your child questions about your medical history, health, and the medicines you are taking. Your 
medical records may be reviewed, if available, to assess your health. 

You/your child can have only clear liquids (e.g., no food) for 4 hours prior to their scheduled start time. Standard 
meals will be provided (see table below).

You or your child will have one brain scan called an fMRI (see 
picture) before taking naltrexone and one brain scan after to look at 
response to naltrexone. During the brain scan, you/your child will 
view pictures of food and play a game.

We will be collecting blood and urine samples for 7 hours after 
you/your child takes naltrexone. To minimize the discomfort 
associated with repeated blood draws, blood will be collected through 
an IV (small tube in the arm) on the Study Day whenever possible 
(needle stick may be used if needed or you/your child prefers). We 
will take less than 1 teaspoon of blood at each collection. The total 
blood collected for the study will be no more than 8 teaspoons during the Study Day. All urine will be collected 
during the study day and a small amount stored.
Study Visit Element 
Main Procedures/Data Collected
Approximate Clock 
Time 
Screening and Consent 
Review inclusion and exclusion criteria, Consent
In person, telephone or e-
consent prior to study visit
Vital signs and medical history
Inclusion/exclusion criteria review and confirmation, 
medical history, height, blind weight (not shared with 
participant), blood pressure, pulse pregnancy test (for 
participants of reproductive potential)
7 am 
Meal #1 (1 hour before scan #1) 
Standardized meal 
8 am 
fMRI scan #1 
During the brain scan, you/your child will view pictures 
of food and play a game.
9 am 
Naltrexone (NTX) dosing 
Single dose of naltrexone by mouth 2 hours prior to 
scan #2 
10:30 am 
Meal #2 (1 hour before scan #2) 
Standardized meal 
11:30 pm 
fMRI scan #2 (2 hours post-
NTX) 
During the brain scan, you/your child will view pictures 
of food and play a game.
12:30 pm 
Pharmacokinetic analysis 
Blood samples obtained from IV pre-dose, 0.5, 1, 1.5, 
2, 3, 4, 6, 7 hours post-naltrexone dose. 
5:30 pm  
(last PK draw & study 
end) 
OPTIONAL EEG: Some participants may qualify to have an EEG done before taking naltrexone. An EEG involves 
wearing a special cap that measures brain signals. 
For participants under 18: Information and samples will be stored past your child’s 18th birthday. We will attempt to 
contact your child for verbal consent once they turn 18. If we cannot reach your child, all samples and information will be 
de-identified. 
IRB Effective Date: 6/1/2021


 Naltrexone Neuroimaging
IRB # 00001668
Page 3 of 6
For all participants: Samples will be stored and used only for research and will not be sold. This research might include 
looking at you/your child’s genetic code (e.g., genome sequencing or genetic analysis), at blood markers or medication 
levels. A human cell contains thousands of genes. Genes contain the information needed to build and operate a human 
body.  The basic structure of genes is DNA, which stands for deoxyribonucleic acid.  Everyone’s genes are different. This 
explains differences in eye color, hair color, and blood type.  Gene differences also partly explain why some people, but 
not others, get certain diseases.  Information about gene differences among people can help researchers discover new tools 
to diagnose and treat inherited diseases. DNA testing will be done on your child’s sample collected for this study. You or 
your child’s de-identified information and samples could be used for future research without additional permission. 
The fMRI and genetic results will not be shared with you/your child. Aggregate de-identified study findings will be 
available to participants in peer-reviewed scientific publication, a process which can take years. If you/your child want to 
be sent a copy of the publication(s), please indicate so at the end of this form. 
You should know that research sometimes results in discoveries that may one day have commercial value. For example, 
discoveries could eventually lead to new tests, drugs, or other products. Development of new products relies on the study 
of samples from hundreds or thousands of people, not on any one person. If this happens, you or your child should not 
expect to share in any of the profits. You and your child will not receive money or other compensation for use of these 
samples. 
Optional Future Research Contact: You will be asked whether we may contact you in the future about your child taking 
part in future research studies related to your child’s disease or condition. Your decision will not affect your child’s ability 
to be in this research study and will not affect your child’s routine care.  You will be able to mark your choice at the end 
of this form.
WHAT ARE THE RISKS OF THE STUDY? 

Small risk of loss of confidentiality because we are keeping your identified study records, but every effort will be 
made to prevent this and keep your information confidential. By providing your email or phone number, the study 
team may communicate with you regarding setting up appointments, sending copies of permission/assent forms 
and any other non-clinical, study related communication. If you are enrolled in the My Children's Mercy Portal, 
the study team may also communicate with you via the portal. Please be aware of the following:
o
Corresponding through electronic communication methods is not a secure method of sending 
information and others may be able to access the information sent.
o
The information may not be secure if storing or viewing the permission/assent document on a personal 
electronic device (PED), especially if that PED is shared with other users or is lost, hacked, or subject to a 
search warrant or subpoena. 
o
Information that is sent electronically may be kept on the Hospital's or your service provider's (Google, 
Yahoo, MSN, etc) network servers. Unlike paper copies, e-copies delivered directly to your PED may not 
be able to be permanently removed.
o
Information shared through the portal may be saved as a part of your child's permanent medical record. 
o
The Hospital is not liable for any security breaches of your information sent electronically.
o
Under Missouri law, a competent minor (less than 18 years old) may consent to his or her own diagnosis 
or treatment without parental permission for reproductive health care, drug or substance abuse. Negative 
test results cannot be released to a parent or guardian without the minor’s permission. Positive test results 
can be discussed with the parent or guardian at the discretion of the provider. Because pregnancy testing 
is being done as part of this study, this privacy protection is not possible. If participants do not want these 
test results shared, they should not enroll in the study.

Minimal discomfort or bruising may occur with drawing blood and IV placement. You/your child may be given 
the option of a numbing agent to help ease the pain of needle sticks.

When answering the brief questionnaires, the questions asked may be uncomfortable or embarrassing. These risks 
are minimum and unlikely to occur. You or your child do not have to give any information you do not want to 
give. You or your child’s confidentiality will be protected to the greatest extent possible and your answers will not 
be released to your care team. 

Side effects to naltrexone occur in ~10% of patients, are typically mild and go away on their own (e.g., nausea) 
and do not differ from those receiving a placebo (e.g., sugar pill). Allergic reaction to naltrexone is rare and 
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usually happens right away after taking the medicine. Symptoms include hives and difficulty breathing. Trained 
personnel will be available in the clinic where the study drug is given. Caution is advised with naltrexone use in 
pregnancy, although there is no expected risk of harm to an unborn baby based on available information.  If 
you/your child is pregnant, you cannot be in this study. 

Genetic testing carries the possibility of discrimination. However, a Federal law called the Genetic Information 
Nondiscrimination Act (GINA) generally makes it illegal for health insurance companies, group health plans, and 
most employers to discriminate based on genetic information. Additionally, you/your child’s results will be kept 
in the study record and not released to your medical record. 

Some patients may feel claustrophobic during the brain scan; however, only a small amount of the upper body 
will be in the scanner. Incidental finding from the neuroimaging (e.g., fMRI) may occur. Whenever brain imaging 
is done, there is a chance of finding something unexpected and unrelated to the research study that may have some 
clinical implications. The neuroimaging used in this study is for research purposes only and is not the same as 
clinical neuroimaging.  
If you have any of these problems or changes in the way you/your child feel, you/your child should tell the investigator or 
other study personnel as soon as possible.
WHAT ARE THE BENEFITS OF BEING IN THIS STUDY?
There may be a direct benefit to you/your child from being in this study.  Possible benefits may include reduction in 
eating disorder symptoms, such as urge to binge eat or purge (e.g., vomit) after taking naltrexone.  By being in this study, 
you/your child may help teens and young adults with eating disorders in the future.
WHAT ABOUT EXTRA COSTS AND INSTITUTIONAL RESPONSIBILITIES? 
You will not have to pay anything extra if you or your child are in this study and nothing will be billed to your insurance. 
Naltrexone and meals will be provided to you at no charge. Basic expenses such as transportation and the personal time it 
will take to come to the study visit will be your responsibility
Research-related injury is not expected and no compensation for research-related injury is available. Should a 
serious adverse event occur during the study day, you/your child will be taken to the nearest emergency 
department or the emergency department of your choice. Care will be provided by that institution at the usual 
charge and you/your child will have the benefit of the coverage of any existing health insurance you own. You 
will be responsible for any treatment costs not covered by any existing health insurance/third-party payor. 
WHAT ABOUT CONFIDENTIALITY?
The information we collect about you or your child during this study will be stored in the research record on a secure 
server at Children’s Mercy and may also be recorded in you/your child’s medical record. The research record is separate 
from the medical record. This record will have you or your child’s name, contact info, medical record number, date of 
birth, medical history and research data. We will do our best to protect this information so that no one else can see it. You 
or your child’s answers to the questionnaires will not be shared with the clinical team. We believe this will allow you or 
your child to provide honest answers without fear of negative consequence. 
By signing this form, you are allowing the research team to keep this information. The law says we must keep this 
information secure and private. All research records will be maintained in a confidential manner.
By signing this form, you are also permitting the following people to have access to you/your child’s medical record and 
PHI:
•
The research team, which includes persons involved in this study at Children’s Mercy Hospital and the 
University of Kansas Medical Center
•
Hoglund Biomedical Imaging Center
•
The Institutional Review Board at Children’s Mercy Hospital and the University of Kansas Medical Center
•
A group that oversees the data (study information) and safety of this research
•
People from organizations that provide independent accreditation and oversight of hospitals and research
•
Government/regulatory agencies such as the Office for Human Research Protections whose job it is to protect 
human subjects and oversee the conduct of research 
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Information (e.g., name, contact info, date of birth, SSN only if needed) will remain on the Greenphire secure server 7 
years after study closure and then will be destroyed.  This information is needed for tax purposes related to compensation 
only.
WHAT ARE THE ALTERNATIVES TO BEING IN THIS STUDY?
Participating in research is your choice. You/your child can choose not to participate. 
WHAT WILL I RECEIVE FOR BEING IN THIS STUDY
You or your child will receive $400 for completing the Study Day. Standard meals will also be provided during the study 
day. 
If you receive a total of over $600 in the calendar year from Children’s Mercy for participating in research, the IRS 
requires the collection of your social security number (SSN) or individual tax identification number (ITIN) and you will 
receive a copy of this tax form. If collected, your SSN or ITIN will be kept securely.  Accepting payment for taking part 
in the study may affect eligibility for Medicaid or other programs. 
WHAT ARE MY RIGHTS AS A STUDY PARTICIPANT?
Being in a research study is voluntary.  You do not have to be in this study to receive medical care at Children’s Mercy.  If 
you choose not to be in this study or withdraw from this study, there will be no penalty or loss of benefits to which you 
are otherwise entitled.  If you are an employee of Children’s Mercy, your decision will not impact your employment.
WHO SHOULD I CALL IF I HAVE QUESTIONS OR PROBLEMS?
Stephani Stancil, PhD, APRN is in charge of this research study. You may call her at 816-960-3040 with questions at any 
time during the study. You should call Dr. Stancil if you believe that you or your child has suffered injury of any kind as a 
result of being in this research study. 
You may also call Children’s Mercy Hospitals’ Pediatric Institutional Review Board (IRB) at (816) 731-7474 with 
questions, compliments or complaints about this study.  The IRB is a committee of physicians, statisticians, researchers, 
community advocates, and others that ensures that a research study is ethical and that the rights of study participants are 
protected.
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PERMISSION/CONSENT OF PARTICIPANT
The purposes, procedures, and risks of this research study have been explained to me.  I have had a chance to read and 
discuss this form and ask questions about the study.  Any questions I had have been answered to my satisfaction.  I 
understand that I/my child don’t/doesn’t have to be in the study and can quit at any time.  A copy of this signed form will 
be given to me.
PERMISSION/CONSENT: 
I give permission or provide consent for _____________________________________ to participate in this 
research study.
 
_________________________________________________________ _____________________
 Signature of Adult Participant or Parent/LAR                                     Date        Relationship to Participant 
ASSENT OF MINOR: 
I agree to be in the study and with the paragraph above. 
________________________________________________________________                     
                              
Signature of minor                                            Date
Optional Future Research Contact:
I agree for a member of the Children’s Mercy study team to contact me in the future to ask about me /my 
child participating in future research studies.
 ______Yes_______No________Initials
I would like to be sent a copy of the scientific publication(s) that contain de-identified, aggregate 
findings from this study. 
______Yes_______No________Initials
STUDY PERSONNEL
I have explained the purposes, procedures, and risks involved in this study in detail to:
_________________________________________________
Print name(s) of Adult Participant/Parent/LAR
________________________________________
______________
________________
Signature of Person Obtaining Permission/Assent/Consent
Date
Time
Print Name of Person Obtaining Permission/Assent/Consent __________________________
INTERPRETER
 
 Interpreter Used 
 
Qualified Bilingual Study Staff Used
I was present and provided interpretation services during the signing of this document.
___________________________________
______________
Signature of Interpreter
Date
Printed Name of Interpreter: ________________________ 
(Must also sign the translated document)
Relationship of Interpreter to Participant/Parent/LAR:______________________
IRB Effective Date: 6/1/2021