Naltrexone Neuroimaging in Teens With Eating Disorders (NN-RCT)

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

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).

Study Overview

• Status: Recruiting
• Conditions: Bulimia Nervosa; Binge Eating; Purging (Eating Disorders); Eating Disorders; Anorexia Nervosa, Atypical
• Intervention / Treatment: Drug: Naltrexone; Drug: Placebo

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)).

• Study Type: Interventional
• Enrollment (Estimated): 60
• Phase: Early Phase 1

Contacts and Locations

• Study Contact: Name: John Tumberger, BS; Phone Number: 8164829872; Email: jtumberger@cmh.edu
• Study Contact Backup: Name: Stephani Stancil, PhD; Email: slstancil@cmh.edu

Study Locations

• United States
  • Missouri
    • Kansas City, Missouri, United States, 64108
      • Recruiting
      • Children's Mercy Research Institute
      • Principal Investigator: Stephani L Stancil, PhD, APRN
      • Contact: John Tumberger, BS; Phone Number: 816-731-7189; Email: jtumberger@cmh.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 13 years to 21 years (Child, Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Group A; 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; 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.; 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.
Experimental: Group B; 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; 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.; 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.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Children's Mercy Hospital Kansas City
• Collaborators: University of Kansas Medical Center

Study record dates

Study Major Dates

• Study Start (Actual): September 17, 2022
• Primary Completion (Estimated): September 1, 2026
• Study Completion (Estimated): June 1, 2027

Study Registration Dates

• First Submitted: August 17, 2022
• First Submitted That Met QC Criteria: August 18, 2022
• First Posted (Actual): August 22, 2022

Study Record Updates

• Last Update Posted (Actual): October 12, 2023
• Last Update Submitted That Met QC Criteria: October 10, 2023
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Keywords: Adolescent; Pediatric; Naltrexone; Neuroimaging; Eating Disorder; Pharmacodynamic Biomarker
• Additional Relevant MeSH Terms: Mental Disorders; Signs and Symptoms, Digestive; Hyperphagia; Anorexia; Anorexia Nervosa; Bulimia; Feeding and Eating Disorders; Bulimia Nervosa; Physiological Effects of Drugs; Peripheral Nervous System Agents; Sensory System Agents; Narcotic Antagonists; Alcohol Deterrents; Naltrexone
• Other Study ID Numbers: STUDY00002228

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No