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| ID | Type | Description | Link |
|---|---|---|---|
| K23MH130728 | U.S. NIH Grant/Contract | View source |
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| Name | Class |
|---|---|
| University of Kansas Medical Center | OTHER |
| National Institute of Mental Health (NIMH) | NIH |
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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).
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)).
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Group A | Experimental | 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. |
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| Group B | Experimental | 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. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Naltrexone | Drug | 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. |
| 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) |
| 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) |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Mariah L Brewe, BA | Contact | (816) 916-3409 | mbrewe@cmh.edu | |
| Stephani Stancil, PhD | Contact | slstancil@cmh.edu |
| Name | Affiliation | Role |
|---|---|---|
| Stephani Stancil, PhD | Children's Mercy Hospital Kansas City | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Children's Mercy Research Institute | Recruiting | Kansas City | Missouri | 64108 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 40043750 | Derived | Stancil SL, Brewe ME, Tumberger J, Bartkoski M, Burns A, Yeh HW, Brucks MG, Bartolotti J, Voss M, Strawn JR, Abdel-Rahman S, Davis A, Brooks WM, Martin LE. 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. 2025 May;152:107874. doi: 10.1016/j.cct.2025.107874. Epub 2025 Mar 3. |
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| ID | Term |
|---|---|
| D001068 | Feeding and Eating Disorders |
| D002032 | Bulimia |
| D052018 | Bulimia Nervosa |
| D000856 | Anorexia Nervosa |
| ID | Term |
|---|---|
| D012817 | Signs and Symptoms, Digestive |
| D012816 | Signs and Symptoms |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D001523 | Mental Disorders |
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| ID | Term |
|---|---|
| D009271 | Naltrexone |
| ID | Term |
|---|---|
| D009270 | Naloxone |
| D009019 | Morphinans |
| D053610 | Opiate Alkaloids |
| D000470 | Alkaloids |
| D006571 |
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| Placebo | Drug | 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. |
|
Naltrexone systemic exposure defined by the pharmacokinetic parameter AUC
| Blood sampled 0-7 hours post medication |
| D006963 | Hyperphagia |
| Heterocyclic Compounds |
| D006572 | Heterocyclic Compounds, Bridged-Ring |
| D006576 | Heterocyclic Compounds, 4 or More Rings |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D010616 | Phenanthrenes |
| D011084 | Polycyclic Aromatic Hydrocarbons |
| D011083 | Polycyclic Compounds |