Clinical trial NCT05509257: Naltrexone Neuroimaging in Teens with Eating Disorders
Official title: Development of a Pharmacodynamic Biomarker of Opioid Antagonism in Adolescents with Eating Disorders
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: EARLY_PHASE1
Conditions: Eating Disorders
Binge Eating
Purging (Eating Disorders)
Bulimia Nervosa
Anorexia Nervosa, Atypical
Keywords: Pediatric
Adolescent
Eating Disorder
Neuroimaging
Naltrexone
Pharmacodynamic Biomarker
Lead sponsor: Children's Mercy Hospital Kansas City
Sponsor class: OTHER
Collaborators: name: University of Kansas Medical Center
name: National Institute of Mental Health (NIMH)
First posted: 2022-08-22
Enrollment: 60
Sex: ALL
Minimum age (years): 13
Maximum age (years): 21
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: OTHER

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)).

Eligibility criteria: 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.

Primary outcomes:
measure: Response
timeFrame: 2 hours post medication (naltrexone or placebo)
Secondary outcomes:
measure: Maximum Concentration in Plasma (Cmax)
timeFrame: Blood sampled 0-7 hours post medication
measure: Area Under the Plasma Concentration vs. Time Curve (AUC)
timeFrame: Blood sampled 0-7 hours post medication
Other outcomes:
Locations:
city: Kansas City
country: United States
facility: Children's Mercy Research Institute
state: Missouri
Study officials:
References: