Low-Dose Naltrexone for Endometriosis

Overseen By Robinn Moyer, BS

Age: 18 - 65

Sex: Female

Trial Phase: Phase 3

Sponsor: Milton S. Hershey Medical Center

Must be taking: Norethindrone acetate

Must not be taking: Thioridazine, Opioids

Disqualifiers: Pregnancy, Liver disease, Cancer, others

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

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

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 5

Duration: 12 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether adding Low-Dose Naltrexone, a medication that can help with pain, to standard treatments for endometriosis can better relieve patient-reported pain. The study compares the effects of Naltrexone combined with usual medication versus a placebo (a sugar pill), also combined with usual medication, over 12 weeks. Women who might be suitable candidates are those diagnosed with endometriosis, have undergone surgical confirmation within the last 10 years, and experience pain related to the condition. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking treatment advancements.

Will I have to stop taking my current medications?

You may need to stop some medications. Participants must agree to use only study-specific pain medications and may need to switch to Norethindrone acetate if using certain contraceptives or endometriosis treatments.

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

Research has shown that Low-Dose Naltrexone (LDN) is generally safe and well-tolerated. One study found LDN to be a safe option for people with fibromyalgia, a condition causing widespread pain. Although the data remain early, these studies have reported no major side effects.

Naltrexone already has FDA approval for other uses, such as treating opioid addiction, indicating its safety has been thoroughly evaluated for those purposes. However, like any medication, it can cause side effects. Some individuals might experience minor issues like nausea or headaches, but serious side effects are rare.

For those considering joining a trial using LDN, it is reassuring that the treatment has a good safety record in similar conditions. Always consult a healthcare provider to understand what this means for individual health needs. ^{1 2 3 4 5}

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

Researchers are excited about low-dose naltrexone for endometriosis because it offers a novel approach to managing the condition by modulating the immune system and reducing inflammation. Unlike the current standard treatments, which often focus on hormonal therapy to control pain and growth of endometrial tissue, naltrexone works differently by targeting the body's endorphin and immune pathways. This could potentially lead to fewer side effects and provide relief for those who don't respond well to hormonal treatments. By combining naltrexone with standard therapies like norethindrone acetate, there's hope for improved pain management and better quality of life for patients.

What evidence suggests that Low Dose Naltrexone might be an effective treatment for endometriosis?

Research has shown that low-dose naltrexone (LDN), which participants in this trial may receive, might help reduce pain in conditions like endometriosis. It reduces inflammation and aids the immune system. Studies have found that LDN can lessen pain in other long-term conditions by altering pain perception. Although specific research on endometriosis remains limited, early signs suggest it could enhance standard treatments. This trial will compare LDN with a placebo to evaluate its potential to improve overall pain relief for women with endometriosis. ^{6 7 8}

Who Is on the Research Team?

Kristin Riley, MD

Principal Investigator

Milton S. Hershey Medical Center

Are You a Good Fit for This Trial?

Inclusion Criteria

Must agree to use only study-specific analgesic medications during the study and is not known to be intolerant to them.

Diagnosed with endometriosis and has had, within the last 10 years prior to signing the informed consent, surgical diagnosis with direct visualization and/or histopathologic confirmation of endometriosis.

Is not expected to undergo gynecological surgery or other surgical procedures for treatment of endometriosis during the study period.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either low-dose naltrexone or placebo in combination with standard treatment for endometriosis over a 12-week period

12 weeks

4 visits (in-person) at baseline, 4, 8, and 12 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

1 visit (in-person) at 16 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Naltrexone

How Is the Trial Designed?

Group I: Low-Dose Naltrexone Experimental Treatment 2 Interventions

12-week intervention period of 4.5 mg daily naltrexone in combination with standard treatment of 5-15 mg daily norethindrone acetate

Group II: Placebo Placebo Group 2 Interventions

12-week intervention period of daily placebo in combination with standard treatment of 5-15 mg daily norethindrone acetate

Who Is Running the Clinical Trial?

Milton S. Hershey Medical Center

Lead Sponsor

Trials

515

Recruited

2,873,000+

Published Research Related to This Trial

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]

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]

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]

Induction success for extended-release naltrexone (XR-NTX) is significantly lower in individuals requiring opioid detoxification (62.6%) compared to those already detoxified (85.0%), indicating that detoxification status is crucial for treatment initiation.

Adherence to XR-NTX is relatively low, with only 44.2% of individuals completing all scheduled injections, and adherence rates are notably higher in controlled research settings compared to routine care, which limits the overall effectiveness of XR-NTX in clinical practice.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Extended-release injectable naltrexone for opioid use disorder: a systematic review. Jarvis, BP., Holtyn, AF., Subramaniam, S., et al.[2019]

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]

In a study of 603 participants from the COMBINE Study, family history of alcoholism (FHA) was linked to increased alcohol consumption per drinking occasion, indicating that individuals with a stronger FHA may drink more when they do drink.

While naltrexone showed a significant effect on reducing heavy drinking days over time, the study found that FHA did not significantly influence the effectiveness of naltrexone, suggesting that other factors may be more important in determining treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Does family history of alcoholism moderate naltrexone's effects on alcohol use? Capone, C., Kahler, CW., Swift, RM., et al.[2019]

Injectable formulations of naltrexone, such as Vivitrex/Vivitrol and Naltrel, show promise in treating alcohol dependence with potentially fewer side effects compared to oral naltrexone, which has limitations like a small treatment effect size and plasma level fluctuations.

Vivitrex/Vivitrol has been effective in reducing heavy drinking in alcohol-dependent males, while Naltrel has been shown to promote abstinence and reduce relapse rates, indicating that these depot formulations may offer improved therapeutic options for alcohol dependence.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Naltrexone long-acting formulation in the treatment of alcohol dependence. Johnson, BA.[2021]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT03970330

Study Details | NCT03970330 | Low-Dose Naltrexone in ... The central hypothesis of the research study is that low dose naltrexone (LDN), in ... REVIA. Drug : Norethindrone Acetate. 5 - 15mg daily dose, taken orally.

2. withpower.com withpower.com/trial/phase-3-endometriosis-7-2004-f549f

Norethindrone Acetate vs. GnRH Agonist for Endometriosis What data supports the effectiveness of the drug Lupron Depot ... Low-Dose Naltrexone for Diabetic Neuropathy. See More. Related Searches. CHAMP ...

3. medicopharm.com medicopharm.com/naltrexone-low-loss-dose-weight-3762246/when-should-you-take-low-dose-naltrexone

Naltrexone when low? market What pain pill can you take when on low dose naltrexone. Naltrexone (ldn) or hydroxychloroquine (hcq) have been marketed globally but are not ...

4. vivitrol.com vivitrol.com/important-safety-information

Important Safety Information VIVITROL can cause serious side effects, including: Risk of opioid overdose. You can accidentally overdose in two ways.

5. 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 ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10039621/

The Safety and Efficacy of Low-Dose Naltrexone in Patients ... LDN appears to be a safe and efficacious treatment option in patients with FM. The current clinical data supporting its use are preliminary; ...

7. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/label/2013/018932s017lbl.pdf

REVIA (naltrexone hydrochloride tablets USP) 50 mg Opioid ... Cases of opioid overdose with fatal outcomes have been reported in patients after discontinuing treatment. Patients should be alerted that they may be more ...

8. mayoclinic.org mayoclinic.org/drugs-supplements/naltrexone-oral-route/description/drg-20068408

Naltrexone (oral route) - Side effects & dosage Naltrexone is used to help patient with opioid use disorder who have stopped taking opioids to stay drug-free and maintain their recovery.