Naltrexone for Eating Disorders

(NN-RCT Trial)

Overseen By Mariah L Brewe, BA

Age: < 65

Sex: Any

Trial Phase: Phase < 1

Sponsor: Children's Mercy Hospital Kansas City

Must not be taking: Naltrexone, Opioids

Disqualifiers: Pregnancy, Metal implants, Language barrier, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 2

Duration: 4 weeks

60 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests how naltrexone, a medication, affects brain activity in young people with eating disorders like binge eating or purging. Researchers aim to determine if brain scans can reveal changes in the brain's reward system when participants take naltrexone. Participants will try both naltrexone and a placebo at different times to compare effects. Suitable candidates for this trial are adolescents aged 13-21 with a stable medication routine and an eating disorder involving binge eating or purging. As an Early Phase 1 trial, this research focuses on understanding how naltrexone works in people, offering participants a chance to contribute to groundbreaking insights.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but it requires that your medication regimen has been stable for at least 4 weeks before joining. This means no changes in dose or type of medication during that time.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that naltrexone has been studied for its safety in treating various conditions, including eating disorders. The FDA has already approved naltrexone for treating opioid addiction and alcohol dependence, indicating its well-established safety in humans.

Studies have found that naltrexone can help reduce binge eating and purging in teenagers with eating disorders. Although this is an early-stage trial, these results suggest that naltrexone might be well-tolerated. Common side effects in other uses include nausea, headache, and dizziness, but serious side effects are rare.

In this trial, all participants will receive both naltrexone and a placebo at different times. This approach helps the researchers understand its direct effects and any side effects. While more research is needed to confirm these findings specifically for eating disorders, the current data offers a promising view on the safety of naltrexone. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for eating disorders?

Unlike the standard treatments for eating disorders, which often focus on therapy and nutritional education, naltrexone is unique because it targets the brain's opioid receptors. By blocking these receptors, naltrexone may reduce the rewarding aspects of eating, especially binge eating, offering a new approach to managing eating disorders. Researchers are excited about this treatment because it represents a novel mechanism of action that could complement existing therapies, potentially leading to more effective and comprehensive treatment plans for individuals struggling with these challenging conditions.

What evidence suggests that naltrexone might be an effective treatment for eating disorders?

Research has shown that naltrexone may help reduce binge eating and purging in teenagers with eating disorders. In this trial, participants will receive both naltrexone and a placebo in a randomized, crossover fashion. Earlier studies demonstrated that naltrexone, a drug that blocks certain signals in the brain, may affect the brain's reward system. This system likely plays a role in the compulsive behaviors seen in eating disorders. Early results suggest that naltrexone could alter activity in specific brain areas related to reward and impulse control. While more research is needed to confirm its effectiveness, these findings offer hope for naltrexone's role in treating eating disorders. ^{1 2 3 5 6}

Who Is on the Research Team?

Stephani Stancil, PhD

Principal Investigator

Children's Mercy Hospital Kansas City

Are You a Good Fit for This Trial?

Adolescents and young adults aged 13-21 with an eating disorder characterized by binge eating and/or purging can join this trial. They must have a stable medication regimen, be able to give informed consent, and not be allergic to naltrexone or pregnant. Those with metal implants incompatible with MRI or recent opioid use are excluded.

Inclusion Criteria

I have been diagnosed with an eating disorder that involves binge eating or purging.

My medications have not changed in the last 4 weeks.

I am between 13 and 21 years old.

Exclusion Criteria

Non-removable metal in the body that is magnetic resonance imaging incompatible

A language barrier (e.g., non-English speaking) for the participant that precludes communication and/or ability to complete all study-related requirements

Self-reported opioid use in the past 7 days

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive naltrexone and placebo in a randomized, crossover fashion with a washout period

4 weeks

2 visits (in-person)

Washout

A washout period of at least 14 days to exceed the 48-hour carry-over effect from naltrexone

2 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Naltrexone
• Placebo

Trial Overview The study is testing if fMRI can show changes in the brain's reward system when given Naltrexone, an opioid blocker, compared to a placebo. Participants will randomly receive either Naltrexone or placebo first, then switch to the other after a period of time.

How Is the Trial Designed?

Group I: Group B Experimental Treatment 2 Interventions

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.

Group II: Group A Experimental Treatment 2 Interventions

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.

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

Approved in United States as Vivitrol for:

• Alcohol dependence
• Opioid use disorder

Approved in European Union as Naltrexone for:

• Opioid dependence
• Alcohol dependence

Approved in Canada as Vivitrol for:

• Opioid use disorder
• Alcohol dependence

Who Is Running the Clinical Trial?

Children's Mercy Hospital Kansas City

Lead Sponsor

Trials

261

Recruited

941,000+

University of Kansas Medical Center

Collaborator

Trials

527

Recruited

181,000+

National Institute of Mental Health (NIMH)

Collaborator

Trials

3,007

Recruited

2,852,000+

Published Research Related to This Trial

In a study of 205 adults with binge eating disorder, rapid response (≥70% reduction in binge eating by Week 4) was a strong predictor of long-term remission, particularly in those receiving cognitive-behavioral therapy guided self-help (CBTgsh).

While rapid responders in CBTgsh showed sustained remission and lower eating disorder psychopathology, interpersonal psychotherapy (IPT) was equally effective for both rapid and nonrapid responders, suggesting it could be a valuable second-line treatment for those who do not respond quickly to CBTgsh.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rapid response in psychological treatments for binge eating disorder. Hilbert, A., Hildebrandt, T., Agras, WS., et al.[2022]

Currently, the only established medications for bulimia nervosa (BN) are antidepressants, particularly selective serotonin reuptake inhibitors (SSRIs), and the antiepileptic drug topiramate, though their effectiveness is only modest.

There is ongoing research into various medications, including fluoxetine and intranasal naloxone, as well as potential new treatments like nociceptin receptor antagonists, indicating a need for further development of specific pharmacological agents for BN.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Progress in Developing Pharmacologic Agents to Treat Bulimia Nervosa. McElroy, SL., Guerdjikova, AI., Mori, N., et al.[2020]

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]

In a small study of 10 individuals with bulimia who did not respond to traditional antidepressants, treatment with the long-acting opiate antagonist naltrexone led to a significant reduction in bulimic symptoms for 7 participants, with improvements lasting for 3 to 5 months.

These findings suggest that naltrexone could be a promising alternative treatment for bulimia, particularly for those resistant to standard therapies, and may help researchers understand the role of opioids in eating disorders.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of antidepressant-resistant bulimia with naltrexone. Jonas, JM., Gold, MS.[2019]

In a pilot study involving 22 adults with binge-eating disorder (BED), the combination of naltrexone and bupropion (NB) was well-tolerated, showing significant reductions in binge-eating frequency, eating-disorder psychopathology, depression, and weight during treatment, although these effects were not significantly different from placebo.

Notably, 45.5% of patients on NB achieved a 3% weight loss compared to none on placebo, indicating a potential benefit of NB for weight management in BED, but further research with a larger sample size is necessary to confirm these findings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Naltrexone + Bupropion Combination for the Treatment of Binge-eating Disorder with Obesity: A Randomized, Controlled Pilot Study. Grilo, CM., Lydecker, JA., Morgan, PT., et al.[2022]

Naltrexone was effective in reducing bulimic symptoms over a 16-month period in a single subject, showing improvements in binge and purge behaviors, urges, and overall eating patterns.

The study also reported a rare allergic reaction to naltrexone, which was heat and photosensitive, highlighting the importance of monitoring for side effects even after desensitization.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A detailed longitudinal analysis on the use of naltrexone in the treatment of bulimia. Marrazzi, MA., Kinzie, J., Luby, ED.[2019]

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]

In a single-subject study, naltrexone, an opiate antagonist, significantly reduced binge eating symptoms in a patient with binge eating disorder (BED) compared to placebo, suggesting its potential efficacy for this condition.

The combination of naltrexone and psychotherapy may provide a more effective treatment approach for BED than psychotherapy alone, highlighting the importance of medication in managing this disorder.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Binge eating disorder: response to naltrexone. Marrazzi, MA., Markham, KM., Kinzie, J., et al.[2015]

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]

Citations

1. nationaleatingdisorders.org nationaleatingdisorders.org/

NEDA | Eating Disorders Support, Awareness & Recovery Access support, explore resources, join community events, and take a free eating disorders screening—start your recovery journey with NEDA!

2. sciencedirect.com sciencedirect.com/science/article/abs/pii/S1551714422002634

An experimental protocol for a double-blind placebo ... This double-blind, placebo-controlled study evaluates the effectiveness of oral naltrexone in adolescents and young adults with eating disorders (EDs)

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6822572/

Naltrexone Reduces Binge Eating and Purging in ... Objective: Little evidence exists for pharmacologic treatment of binge eating and purging in adolescents with eating disorders. Given the role of the opioid ...

4. psychiatryonline.org psychiatryonline.org/doi/full/10.1176/appi.ajp.20220267

Naltrexone-Bupropion and Behavior Therapy, Alone ... One FDA-approved obesity medication, a naltrexone-bupropion combination (22), is a logical treatment to consider for binge-eating disorder ...

5. clinicaltrials.gov clinicaltrials.gov/study/NCT05073679

Oral Naltrexone In Pediatric Eating Disorders Electing to participate in child or adult partial hospitalization program for eating disorder treatment at MSHMC. The diagnostic criteria for anorexia nervosa, ...

6. samhsa.gov samhsa.gov/substance-use/treatment/options/naltrexone

What is Naltrexone? Side Effects, Uses, Dose & Risk Intramuscular extended release naltrexone is a medication approved by the Food and Drug Administration (FDA) to treat both opioid use ...