Anorexia Nervosa, Atypical, Binge Eating, Bulimia Nervosa, Eating Disorders, Purging (Eating Disorders)
Conditions
Keywords
Pediatric, Adolescent, Eating Disorder, Neuroimaging, Naltrexone, Pharmacodynamic Biomarker
Brief summary
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
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)).
Interventions
DRUGNaltrexone
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.
DRUGPlacebo
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.
Sponsors
University of Kansas Medical Center
National Institute of Mental Health (NIMH)
Children's Mercy Hospital Kansas City
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
OTHER
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
13 Years to 21 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Response | 2 hours post medication (naltrexone or placebo) | Acute %Blood oxygenation level dependent (BOLD) change placebo vs. naltrexone in pre-defined regions of interest (anterior cingulate cortex, nucleus accumbens, dorsolateral prefrontal cortex) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Maximum Concentration in Plasma (Cmax) | Blood sampled 0-7 hours post medication | Naltrexone systemic exposure defined by the pharmacokinetic parameter Cmax |
| Area Under the Plasma Concentration vs. Time Curve (AUC) | Blood sampled 0-7 hours post medication | Naltrexone systemic exposure defined by the pharmacokinetic parameter AUC |
Countries
United States
Contacts
Primary ContactMariah L Brewe, BA
Backup ContactStephani Stancil, PhD
Outcome results
None listed