NN-RCT: Naltrexone Neuroimaging Randomized Controlled Trial

Sponsor

Children's Mercy Hospital Kansas City (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT05509257

Collaborator

(none)

Enrollment

Location

Arms

Anticipated Duration (Months)

1.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Using a randomized, placebo-controlled, crossover study, this study will evaluate 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).

Condition or Disease	Intervention/Treatment	Phase
Eating Disorders Binge Eating Purging (Eating Disorders) Bulimia Nervosa Anorexia Nervosa, Atypical	Drug: Naltrexone Drug: Placebo	Early Phase 1

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., AN-B/P, BN, BED). 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 IND exemption, category #1 (21 CFR 312.2(b)(1)).

Study Design

Study Type:

Interventional

Anticipated Enrollment :

60 participants

Allocation:

Randomized

Intervention Model:

Crossover Assignment

Masking:

Double (Participant, Investigator)

Primary Purpose:

Other

Official Title:

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

Anticipated Study Start Date :

Sep 1, 2022

Anticipated Primary Completion Date :

Sep 1, 2026

Anticipated Study Completion Date :

Jun 1, 2027

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Naltrexone	Drug: Naltrexone 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.
Placebo Comparator: Placebo	Drug: Placebo 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.

Arm

Intervention/Treatment

Active Comparator: Naltrexone

Drug: Naltrexone

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.

Placebo Comparator: Placebo

Drug: Placebo

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.

Outcome Measures

Primary Outcome Measures

Response [2 hours post medication (naltrexone or placebo)]
Acute change in %BOLD placebo vs. naltrexone in pre-defined regions of interest (anterior cingulate cortex, nucleus accumbens, dorsolateral prefrontal cortex)

Secondary Outcome Measures

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

Eligibility Criteria

Criteria

Ages Eligible for Study:

13 Years to 21 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Adolescents and young adults aged 13-21 years
DSM-V 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)
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 MR 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.