Naltrexone Neuroimaging in Teens With Eating Disorders

Study Overview
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Brief Summary
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Using a randomized, placebo-controlled, crossover study, this study will evaluate functional magnetic resonance imaging (fMRI) as a pharmacodynamic biomarker of opioid antagonism in adolescents with eating disorders. The hypothesis is that fMRI will be able to detect acute reward pathway modulation by naltrexone (an opioid antagonist) in pre-defined regions of interest (anterior cingulate cortex, nucleus accumbens, dorsolateral prefrontal cortex).

Detailed Description
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The investigators will use a randomized, placebo-controlled, double-blind, crossover trial to evaluate the use of fMRI as a pharmacodynamic biomarker of reward system modulation. The overall goal of this work is to develop an objective tool to detect acute drug response. If validated in future, larger trials, the pharmacodynamic biomarker may facilitate early phase/quantitative pharmacology studies of novel or repurposed agents expected to modulate the reward system. The reward system will be antagonized by naltrexone in adolescents aged 13-21 years with an ED defined by binge/purge behaviors (e.g., Anorexia Nervosa-Binge Purge, Bulimia Nervosa, Binge Eating Disorder). A crossover design was chosen to quantify within-individual change in opioid reward pathway modulation following antagonism. Eligible patients will be randomly assigned to Group A or Group B. A statistician (or other non-study staff) will generate the schedule and communicate with the investigation drug service to maintain the double-blind design. A washout period of at least 14 days will exceed the 48-hour carry-over effect from naltrexone 50 mg administered orally. The two study visits will be mirrored in structure and duration to maintain blinding. 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 the investigational drug service (IDS) pharmacy. Use of naltrexone for this study meets criteria for investigational new drug (IND) exemption, category #1 (21 Code of Federal Regulations (CFR) 312.2(b)(1)).

Official Title
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Development of a Pharmacodynamic Biomarker of Opioid Antagonism in Adolescents With Eating Disorders

Conditions
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Eating Disorders, Binge Eating, Purging (Eating Disorders), Bulimia Nervosa, Anorexia Nervosa, Atypical

Intervention / Treatment
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* Drug: Naltrexone
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adolescents and young adults aged 13-21 years Eating disorder diagnosis characterized by binge eating and/or purging (eg, Anorexia Nervosa-Binge/Purge, Bulimia Nervosa, Binge Eating Disorder, Other Specified Feeding/Eating Disorder) using Diagnostic and Statistical Manual of Mental Disorders, 5th edition (DSM-V) criteria. 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 that is magnetic resonance imaging incompatible 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.

Ages Eligible for Study
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Minimum Age: 13 Years
Maximum Age: 21 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Group A<br>All participants will receive both naltrexone and placebo, separated by a washout period, in a randomized, crossover fashion. Those randomized to group A will receive naltrexone then placebo. Those randomized to group B will receive placebo then naltrexone. | Drug: Naltrexone<br>* Participants will receive a single oral dose in randomized, crossover fashion with a 2 week wash out period between interventions. Medication will be taken 2 hours prior the neuroimaging.<br>Drug: Placebo<br>* Participants will receive a single oral dose of medication in randomized, crossover fashion with a 2 week wash out period between interventions.. Medication will be taken 2 hours prior the neuroimaging.<br>|
| Experimental: Group B<br>All participants will receive both naltrexone and placebo, separated by a washout period, in a randomized, crossover fashion. Those randomized to group A will receive naltrexone then placebo. Those randomized to group B will receive placebo then naltrexone. | Drug: Naltrexone<br>* Participants will receive a single oral dose in randomized, crossover fashion with a 2 week wash out period between interventions. Medication will be taken 2 hours prior the neuroimaging.<br>Drug: Placebo<br>* Participants will receive a single oral dose of medication in randomized, crossover fashion with a 2 week wash out period between interventions.. Medication will be taken 2 hours prior the neuroimaging.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Response | Acute %Blood oxygenation level dependent (BOLD) change placebo vs. naltrexone in pre-defined regions of interest (anterior cingulate cortex, nucleus accumbens, dorsolateral prefrontal cortex) | 2 hours post medication (naltrexone or placebo) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum Concentration in Plasma (Cmax) | Naltrexone systemic exposure defined by the pharmacokinetic parameter Cmax | Blood sampled 0-7 hours post medication | 
| Area Under the Plasma Concentration vs. Time Curve (AUC) | Naltrexone systemic exposure defined by the pharmacokinetic parameter AUC | Blood sampled 0-7 hours post medication | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Pediatric, Adolescent, Eating Disorder, Neuroimaging, Naltrexone, Pharmacodynamic Biomarker