Low-Dose Naltrexone in Combination With Standard Treatment in Women With 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

9 Participants Needed

Trial Summary

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.

What data supports the effectiveness of the drug Naltrexone, Vivitrol, ReVia, Depade?

Research shows that naltrexone, especially in its extended-release form (Vivitrol), is effective in reducing alcohol dependence and opioid use disorder. Studies indicate it helps increase abstinence and reduce heavy drinking days, particularly among men and those with a family history of alcoholism. ^{1 2 3 4 5}

Is naltrexone safe for humans?

Naltrexone, used in various forms like Vivitrol and ReVia, has been studied for safety in different conditions. It can cause liver issues (hepatotoxicity) and has been linked to serious adverse events, but injectable forms may have fewer side effects than oral ones. Concerns about overdose risk after stopping treatment exist, but more research is needed. ^{2 6 7 8 9}

How does this drug differ from other treatments for dyslipidemia?

This drug, Tiadenol, is unique because it is a new hypolipidemic drug that effectively lowers cholesterol and triglyceride levels, similar to clofibrate, but with very good biological tolerability and no reported side effects. ^{10 11 12 13 14}

What is the purpose of this trial?

This trial is testing whether adding a small dose of naltrexone to standard treatments can help reduce pain in patients with endometriosis. Endometriosis often causes significant pain, and current treatments may not be enough. Naltrexone, usually used for addiction, might help by reducing inflammation and calming pain signals. Low-dose naltrexone has been explored as a treatment for various chronic pain conditions, showing potential benefits in reducing pain and inflammation.

Research Team

Kristin Riley, MD

Principal Investigator

Milton S. Hershey Medical Center

Eligibility Criteria

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

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

Treatment Details

Interventions

• Naltrexone

Participant Groups

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+

Findings from Research

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 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]

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]

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]

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]

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]

References

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

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2. 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]

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

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

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

Does family history of alcoholism moderate naltrexone's effects on alcohol use? [2019]

5. England pubmed.ncbi.nlm.nih.gov

Extended-release injectable naltrexone for opioid use disorder: a systematic review. [2019]

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

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

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

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

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

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

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