Clinical Trial Protocol Journal Article Ppublish
PubMed: 40043750 DOI: 10.1016/j.cct.2025.107874
Development of a pharmacodynamic biomarker of opioid antagonism in adolescents with eating disorders: Study protocol for the naltrexone neuroimaging randomized controlled trial (NN-RCT).
Contemp Clin Trials 152:107874
Authors: Stephani L Stancil, Mariah E Brewe, John Tumberger, Michael Bartkoski, Anna Burns, Hung-Wen Yeh, Morgan G Brucks, James Bartolotti, Michaela Voss, Jeffrey R Strawn, Susan Abdel-Rahman, Ann Davis, William M Brooks, Laura E Martin
Affiliations
- Divisions of Adolescent Medicine and Clinical Pharmacology, Toxicology and Therapeutic Innovation, Children's Mercy Kansas City, United States; Department of Pediatrics, University of Missouri-Kansas City School of Medicine, United States; Department of Pediatrics, University of Kansas Medical Center School of Medicine, United States.
- Divisions of Adolescent Medicine and Clinical Pharmacology, Toxicology and Therapeutic Innovation, Children's Mercy Kansas City, United States.
- Department of Pediatrics, University of Missouri-Kansas City School of Medicine, United States; Division of Health Services & Outcomes Research, Children's Mercy Research Institute, United States.
- Department of Population Health, University of Kansas Medical Center, United States.
- Department of Pediatrics, University of Missouri-Kansas City School of Medicine, United States.
- Department of Psychiatry and Behavioral Neuroscience, University of Cincinnati College of Medicine, United States.
- Center for Healthy Lifestyles and Nutrition, University of Kansas Medical Center, United States.
- Department of Neurology, University of Kansas Medical Center, United States; Hoglund Biomedical Imaging Center, University of Kansas Medical Center, United States.
- Department of Population Health, University of Kansas Medical Center, United States; Hoglund Biomedical Imaging Center, University of Kansas Medical Center, United States.
Abstract
Eating disorders (ED) affect 5 % of youth, are associated with reward system alterations, and lead to substantial morbidity. Naltrexone, an opioid antagonist, is used to treat ED behaviors such as binge eating and purging. However, not all patients respond, and the optimal dose is unknown. Neuroimaging may serve as a tool to detect drug response in the brain, acting as a pharmacodynamic biomarker to support therapeutic optimization. Currently, no pharmacodynamic biomarkers for psychopharmacology exist. Building on pilot work, we present the protocol for a randomized controlled trial to validate neuroimaging as a pharmacodynamic biomarker of opioid antagonism in adolescents with ED. Youth aged 13-21 years with binge/purge ED are randomized to receive a single dose of oral naltrexone and placebo in a double-blind using a crossover design with an interdose interval ≥ 2 weeks. Task-based functional neuroimaging detects reward pathway modulation 2 h post-dose. Blood and urine are collected over a model-informed time course. Response (primary outcome) is defined as naltrexone-related blood oxygenation-level dependent signal change (Δ%BOLD) in a priori reward regions of interest and secondary exposure outcomes are naltrexone C and AUC Cohen's d will determine Δ%BOLD effect size, and an exposure-response model will identify target exposure to guide future dosing. This study addresses a critical knowledge gap by developing a non-invasive pharmacodynamic biomarker for youth with ED, with future applications in quantitative pharmacology, precision dosing, and the development of novel therapeutics. NCT05509257.
MeSH
Feeding And Eating Disorders, Eating, Neuroimaging, Naltrexone, Reward, Biomarkers, Adolescent, Pharmacology, Therapeutics