Naltrexone for Eating Disorders

(ONPED Trial)

Overseen By Marley Billman, BS

Age: < 65

Sex: Any

Trial Phase: Phase 2 & 3

Sponsor: Rosemary Claire Roden

Must not be taking: Opioid painkillers

Disqualifiers: Intellectual disability, Genetic disease, Neurologic disease, others

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 2

Duration: 6 weeks

10 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial is testing if naltrexone, a medication taken by mouth, can help children and teenagers with anorexia nervosa and bulimia nervosa. The medication works by blocking certain brain signals related to eating disorder behaviors. Participants will receive either naltrexone or another treatment while continuing their regular care. Naltrexone has been used in various psychiatric conditions, including eating disorders, with variable responses in adults and limited data in children.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, if you are taking opioid painkillers, you cannot participate in the trial.

What evidence supports the effectiveness of the drug naltrexone for treating eating disorders?

Research shows that naltrexone can reduce binge eating and purging behaviors in adolescents and adults with eating disorders. In one study, over half of the adolescents treated with naltrexone showed positive responses, such as reduced purging or the urge to purge. Additionally, naltrexone has been shown to decrease the urge to binge in individuals with bulimia nervosa. ^{1 2 3 4 5}

Is naltrexone generally safe for humans?

Naltrexone has been studied for safety in various conditions, including alcohol and opioid dependence. It is generally considered safe, but there is a potential risk for liver damage (hepatotoxicity) and serious adverse events, especially at higher doses or in people with liver conditions. ^{6 7 8 9 10}

How is the drug Naltrexone unique in treating eating disorders?

Naltrexone is unique in treating eating disorders because it works by blocking opioid receptors in the brain, which can reduce the urge to binge eat or purge. This mechanism is different from other treatments that may not target the opioid reward system, making it a novel option for managing symptoms in conditions like bulimia and anorexia nervosa with bulimic features. ^{1 2 3 4 11}

Research Team

Rosemary C Roden, MD

Principal Investigator

PennState Health Children's Hospital

Eligibility Criteria

This trial is for young people aged 13-25 with eating disorders like anorexia nervosa or bulimia, who are in a hospital program for treatment. They must be able to swallow pills and understand English. Those underweight (<25kg), using opioids, pregnant, lactating, or at high suicide risk can't join.

Inclusion Criteria

My sex does not affect my eligibility.

You have been binge eating and engaging in inappropriate compensatory behaviors at least once a week for the past 3 months.

You have a habit of frequently making yourself vomit or misusing medications to control your weight or body shape.

Exclusion Criteria

Lack of proficiency in written or spoken English

Lactation

I need opioid painkillers for my condition.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

1 week

1 visit (in-person)

Treatment

Participants receive oral naltrexone or placebo daily for 6 weeks while attending a partial hospitalization program

6 weeks

Weekly visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, including completion of various indices

6 months

1 visit (in-person or virtual)

Treatment Details

Interventions

• Naltrexone Hydrochloride

Trial Overview The study tests if oral naltrexone tablets help treat pediatric and adolescent eating disorders compared to a placebo. Participants are already enrolled in intensive outpatient or partial hospitalization programs for their condition.

Participant Groups

Group I: Intervention Experimental Treatment 1 Intervention

Oral naltrexone, to start as 25mg for three days then 50mg a day for 6 weeks. Oral naltrexone generic tabs will be blinded in opaque gelatin capsules with methylcellulose filler

Group II: Control Placebo Group 1 Intervention

Opaque gelatin capsules with methylcellulose filler, taken by mouth once a day for six weeks

Naltrexone Hydrochloride is already approved in United States, European Union for the following indications:

Approved in United States as ReVia for:

• Alcohol use disorder
• Opioid use disorder

Approved in United States as Vivitrol for:

• Alcohol use disorder
• Opioid use disorder

Approved in United States as Depade for:

• Alcohol use disorder
• Opioid use disorder

Approved in European Union as Naltrexone for:

• Alcohol dependence
• Opioid dependence

Who Is Running the Clinical Trial?

Rosemary Claire Roden

Lead Sponsor

Trials

1

Recruited

10+

Children's Miracle Network

Collaborator

Trials

23

Recruited

1,800+

Findings from Research

In a case series of 33 adolescents (average age 15.3 years), naltrexone was found to be safe and well-tolerated, with only 9.1% experiencing nausea, and liver function tests remaining normal for those monitored.

Approximately 67% of the adolescents showed a positive response to naltrexone, indicating reduced purging behaviors, suggesting that it may be an effective treatment option for binge eating and purging in this population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Naltrexone Reduces Binge Eating and Purging in Adolescents in an Eating Disorder Program. Stancil, SL., Adelman, W., Dietz, A., et al.[2020]

This study involves 30 adolescents and young adults with eating disorders, specifically those characterized by purging behaviors, and aims to evaluate the effectiveness of oral naltrexone over six weeks compared to a placebo.

The researchers hypothesize that oral naltrexone will lead to greater improvements in body mass index and self-reported eating disorder symptoms, potentially establishing it as a safe and effective treatment option for impulsive-type eating disorders.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An experimental protocol for a double-blind placebo-controlled evaluation of the effectiveness of oral naltrexone in management of adolescent eating disorders. Roden, RC., Billman, M., Lane-Loney, S., et al.[2023]

In a double-blind clinical trial involving 19 out-patient subjects with bulimia nervosa or anorexia nervosa (bulimic subtype), naltrexone significantly reduced binge-purge behaviors compared to placebo.

The study confirmed the effectiveness of naltrexone through rigorous statistical analysis, showing highly significant differences in symptom reduction, supporting its potential as a therapeutic option for these eating disorders.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Naltrexone use in the treatment of anorexia nervosa and bulimia nervosa. Marrazzi, MA., Bacon, JP., Kinzie, J., et al.[2019]

Selective opioid antagonists like naloxone and naltrexone can reduce food intake by up to 30% and change food preferences in short-term studies involving normal-weight, obese, and bulimic individuals.

However, their long-term effectiveness and safety for treating eating disorders such as Prader-Willi syndrome, obesity, bulimia nervosa, or anorexia nervosa are limited, suggesting that the risks may outweigh the benefits, and further research on newer antagonists is needed.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Opiate antagonists and eating behavior in humans: a review. de Zwaan, M., Mitchell, JE.[2015]

A systematic review of 49 trials found that only 14% of studies on naltrexone for alcohol dependence had high adherence assurance, which may explain the variability in treatment efficacy observed.

The study revealed a significant correlation between adherence levels and treatment outcomes, suggesting that improving adherence monitoring could enhance the effectiveness of naltrexone in clinical settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adherence monitoring in naltrexone pharmacotherapy trials: a systematic review. Swift, R., Oslin, DW., Alexander, M., et al.[2022]

A study involving 250 opioid-dependent patients, many of whom had chronic hepatitis C virus (HCV) and HIV, found that intramuscular extended-release naltrexone (XR-NTX) did not significantly increase liver enzyme levels compared to a placebo, indicating its safety in this population.

Even though some patients experienced elevated liver enzymes, these levels improved over time, and no specific symptoms were linked to these elevations, suggesting that XR-NTX can be safely administered to patients with mild to moderate chronic HCV and/or HIV.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hepatic safety of injectable extended-release naltrexone in patients with chronic hepatitis C and HIV infection. Mitchell, MC., Memisoglu, A., Silverman, BL.[2019]

A review of 263 cases related to Vivitrol (extended-release naltrexone) found that 84.6% of fatal overdoses occurred within two months after the last injection, highlighting a critical period for overdose risk.

The study suggests that there may be a link between Vivitrol discontinuation and increased overdose risk, indicating the need for further investigation and monitoring during this time frame.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Review of Case Narratives from Fatal Overdoses Associated with Injectable Naltrexone for Opioid Dependence. Saucier, R., Wolfe, D., Dasgupta, N.[2019]

In a 1-year open-label extension study involving 114 patients, injectable extended-release naltrexone (XR-NTX) demonstrated long-term efficacy, with 50.9% of participants remaining abstinent from opioids throughout the study.

The treatment was generally safe, with only 21.1% of patients reporting adverse events and no severe adverse events noted, although 16.7% experienced elevated liver function tests.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Injectable extended-release naltrexone for opioid dependence: an open label study of long-term safety and efficacy]. Krupitsky, EM., Nunes, EV., Ling, W., et al.[2016]

References

1. United States pubmed.ncbi.nlm.nih.gov

Naltrexone Reduces Binge Eating and Purging in Adolescents in an Eating Disorder Program. [2020]

2. United States pubmed.ncbi.nlm.nih.gov

An experimental protocol for a double-blind placebo-controlled evaluation of the effectiveness of oral naltrexone in management of adolescent eating disorders. [2023]

3. England pubmed.ncbi.nlm.nih.gov

Naltrexone use in the treatment of anorexia nervosa and bulimia nervosa. [2019]

4. England pubmed.ncbi.nlm.nih.gov

Opiate antagonists and eating behavior in humans: a review. [2015]

5. United States pubmed.ncbi.nlm.nih.gov

Effects of the opiate antagonist, naltrexone, on binging antecedents and plasma beta-endorphin concentrations. [2013]

6. United States pubmed.ncbi.nlm.nih.gov

Adherence monitoring in naltrexone pharmacotherapy trials: a systematic review. [2022]

7. United States pubmed.ncbi.nlm.nih.gov

Hepatic safety of injectable extended-release naltrexone in patients with chronic hepatitis C and HIV infection. [2019]

8. New Zealand pubmed.ncbi.nlm.nih.gov

Review of Case Narratives from Fatal Overdoses Associated with Injectable Naltrexone for Opioid Dependence. [2019]

9. Russia (Federation) pubmed.ncbi.nlm.nih.gov

[Injectable extended-release naltrexone for opioid dependence: an open label study of long-term safety and efficacy]. [2016]

10. England pubmed.ncbi.nlm.nih.gov

Serious adverse events reported in placebo randomised controlled trials of oral naltrexone: a systematic review and meta-analysis. [2023]

11. United States pubmed.ncbi.nlm.nih.gov

Effects of genotype and food on naltrexone exposure in adolescents. [2023]