Naltrexone Neuroimaging (EDIT-N2)

Eating Disorder Individualized Therapeutics-Naltrexone Neuroimaging (EDIT-N2)

The purpose of this open-label, pilot study is to evaluate fMRI as a biomarker of opioid antagonism in adolescents with ED. Modulation of brain activation will be examined in regions of interest by fMRI using a food-specific and general reward task in adolescents with ED in a pre/post design.

Study Overview

• Status: Completed
• Conditions: Binge Eating; Purging (Eating Disorders); Eating Disorders
• Intervention / Treatment: Drug: Naltrexone

Detailed Description

This is an open-label, interventional trial to evaluate reward system modulation (detected by neuroimaging) in response to opioid antagonism (i.e., naltrexone) in adolescents aged 13-21 years with an eating disorder characterized by the target behaviors of binge eating and/or purging (e.g., AN-BP, BN, BED). A pre/post design completed on the same day will be employed to quantify within-individual change while reducing potential confounding due to known neuroimaging variables (e.g., menstrual phase, treatment changes) that may occur with time elapsed between study visits. Self-report data regarding will be captured via electronic surveys using validated instruments (where possible), structured interview, study records.

Reward System Modulation by fMRI. Each scan will last approximately 1 hour and involve two reward activation paradigms: passive food view (PFV) and monetary incentive delay (MID). These two reward activation paradigms provide distinct insight and will generate pilot data to support the choice of the optimal paradigm for further testing of reward system modulation in adolescents with eating disorders. PFV provides a paradigm that is relevant to the target behaviors (i.e., binge eating, purging), has been evaluated in ED patients, in response to naltrexone in adults, and is expected to activate food cue-reactivity regions (e.g., prefrontal cortex). MID is a widely used paradigm in adolescents to detect reward anticipation and receipt particularly in the striatum and is currently being used to study the developmental trajectory of reward processing in the longitudinal Adolescent Brain Cognitive Development (ABCD) trial. To the greatest extent possible, we will harmonize our fMRI parameters with those published for ABCD.

Opioid Antagonism and exposure-response linkage. A single oral dose of naltrexone hydrochloride 50 mg tablet will be administered. Plasma and urine will be obtained to measure systemic exposure to naltrexone and it primary, active metabolite, 6-beta-naltrexol, using a validated UPLC-MS/MS assay.

• Study Type: Interventional
• Enrollment (Actual): 13
• Phase: Early Phase 1

Contacts and Locations

Study Locations

• United States
  • Missouri
    • Kansas City, Missouri, United States, 64108
      • Children's Mercy Research Institute

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Eating disorder diagnosis per DSM-V criteria that is characterized by binge eating (defined as loss of control of eating resulting in large amount of food consumed in a short period of time) and/or purging (e.g., vomiting, excessive exercising, laxative use)
• 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
• 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: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Pilot; Pre/post fMRI	Drug: Naltrexone; naltrexone 50 mg PO x 1

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in % Blood Oxygenation Level Dependent Change (%BOLD) in the Nucleus Accumbens	Change in %BOLD following single dose naltrexone (post-pre) within individuals during passive food view task in the nucleus accumbens	2 hours post-naltrexone vs baseline
Change in % Blood Oxygenation Level Dependent Change (%BOLD) in the Dorsal Anterior Cingulate Cortex	Change in %BOLD following single dose naltrexone (post-pre) within individuals during monetary incentive delay in dorsal anterior cingulate cortex	2 hours post-naltrexone vs baseline

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Exposure	Maximum plasma concentration of naltrexone at 2 hours post-single dose	2 hours post-naltrexone

Collaborators and Investigators

• Sponsor: Children's Mercy Hospital Kansas City
• Collaborators: University of Kansas Medical Center; National Center for Advancing Translational Sciences (NCATS)
• Investigators: Principal Investigator: Stephani Stancil, PhD, Children's Mercy Kansas City

Study record dates

Study Major Dates

• Study Start (Actual): July 16, 2021
• Primary Completion (Actual): June 15, 2022
• Study Completion (Actual): June 30, 2022

Study Registration Dates

• First Submitted: June 15, 2021
• First Submitted That Met QC Criteria: June 15, 2021
• First Posted (Actual): June 23, 2021

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
• Additional Relevant MeSH Terms: Mental Disorders; Signs and Symptoms, Digestive; Hyperphagia; Bulimia; Feeding and Eating Disorders; Physiological Effects of Drugs; Peripheral Nervous System Agents; Sensory System Agents; Narcotic Antagonists; Alcohol Deterrents; Naltrexone
• Other Study ID Numbers: STUDY00001668; UL1TR002366 (U.S. NIH Grant/Contract)

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