Naloxone for Reproductive Disorders

Overseen By Study Coordinator

Age: 18 - 65

Sex: Any

Trial Phase: Phase 1

Sponsor: Stephanie B. Seminara, MD

Must not be taking: Hormonal replacements, Opioid pathway

Disqualifiers: Illicit drug use, Excessive alcohol, others

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

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

Compensation: Varies

Number of Visits: 2

Duration: 12 hours per period

49 Participants Needed

Trial Summary

What is the purpose of this trial?

The goal of this study is to evaluate the effects of opioid antagonists on the hypothalamic-pituitary-gonadal axis in healthy subjects.

Do I need to stop my current medications for the trial?

You may need to stop taking certain medications if they affect the reproductive system or the opioid pathway. If you are on such medications, you might have to go through a washout period (time without taking those medications) before joining the trial.

Is naloxone safe for use in humans?

Naloxone, when combined with buprenorphine, has been shown to be safe and well-tolerated in humans for opioid dependence treatment. Clinical trials have demonstrated that this combination is practical and safe in diverse community settings, with a good safety profile and minimal serious adverse events. ^{1 2 3 4 5}

How is the drug Naloxone unique for treating reproductive disorders?

Naloxone is unique because it is primarily known as an opioid antagonist used to reverse opioid overdoses, and its use for reproductive disorders is novel and not well-studied. This trial explores its potential in a new area, which is different from its traditional use in opioid-related treatments. ^{2 6 7 8 9}

Research Team

Stephanie B. Seminara, MD

Principal Investigator

Massachusetts General Hospital

Eligibility Criteria

Healthy individuals with normal puberty development, no chronic diseases or emergency medication reactions, not on prescriptions except for allergy meds, and not seeking fertility. Must have a BMI between 18.5-30, normal blood pressure and lab results within specific ranges. Men should have normal reproductive function; women need regular menstrual cycles and can't be pregnant or breastfeeding.

Inclusion Criteria

Normal hemoglobin

No excessive alcohol consumption (< 10 drinks/week)

Not currently seeking fertility

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Participants undergo frequent blood sampling and administration of naloxone

12 hours per period

1 visit (in-person) per period

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• GnRH
• Naloxone

Trial Overview The study is testing the impact of opioid antagonists like kisspeptin 112-121, GnRH, and Naloxone on the hormonal system that controls reproduction in healthy subjects to understand how these drugs affect hormone levels.

Participant Groups

Group I: Arm 2 Experimental Treatment 1 Intervention

one period of frequent blood sampling with no medication administered; one period of frequent blood sampling with IV administration of naloxone (one bolus and an infusion over an up to 12-hour period.)

Group II: Arm 1 Active Control 1 Intervention

one period of frequent blood sampling with no medication administered

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

Approved in United States as Naloxone for:

• Opioid overdose reversal

Approved in European Union as Naloxone for:

• Opioid overdose reversal

Approved in Canada as Naloxone for:

• Opioid overdose reversal

Who Is Running the Clinical Trial?

Stephanie B. Seminara, MD

Lead Sponsor

Trials

10

Recruited

840+

Findings from Research

Buprenorphine-naloxone (Suboxone) was found to be safe and well tolerated for short-term opioid detoxification in a study involving 234 opioid-dependent patients across twelve community-based treatment programs.

The treatment showed high medication compliance (81% of doses ingested) and successful induction, with 90% of patients reaching the target dose within three days, indicating its efficacy and practicality in diverse settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bringing buprenorphine-naloxone detoxification to community treatment providers: the NIDA Clinical Trials Network field experience. Amass, L., Ling, W., Freese, TE., et al.[2022]

Buprenorphine is a safe and effective treatment for opioid dependence, particularly when combined with naloxone, which reduces its potential for abuse.

New regulations enable certified physicians to prescribe buprenorphine in their offices, significantly improving patient access to this important treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Buprenorphine maintenance: a new treatment for opioid dependence. Collins, GB., McAllister, MS.[2019]

Extended-release naltrexone (XR-NTX) is viewed positively by patients for its once-monthly dosing and lack of physical dependence, but barriers such as ambivalence and unfamiliarity with antagonist treatment hinder initiation, especially in the context of opioid detoxification.

Once patients initiate XR-NTX, they report it as an effective treatment for opioid use disorder (OUD), with high satisfaction and sustained abstinence, indicating its potential as a viable long-term solution for managing OUD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Patients' perspectives on initiating treatment with extended-release naltrexone (XR-NTX). Gauthier, P., Greco, P., Meyers-Ohki, S., et al.[2022]

Two case studies of pregnant patients with opioid use disorder (OUD) who switched from sublingual buprenorphine to monthly injections of Sublocade® showed no adverse outcomes for either the mothers or their babies, suggesting potential safety in this treatment during pregnancy.

Both patients maintained positive urine drug screens for buprenorphine throughout their pregnancies without experiencing withdrawal symptoms or birth anomalies, indicating that Sublocade may be a viable option for managing OUD in pregnant women, although further research is necessary.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Subcutaneous Extended-Release Buprenorphine Use in Pregnancy. Towers, CV., Deisher, H.[2022]

Buprenorphine is as effective as methadone for opiate detoxification and maintenance but is safer in overdose situations, making it a preferable option for treatment.

Suboxone, a combination of buprenorphine and naloxone, is recommended for maintenance treatment due to its lower abuse potential, while Subutex (buprenorphine alone) is advised for pregnant women, highlighting the tailored approach to treatment based on patient needs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Buprenorphine in the treatment of opiate dependence. Wesson, DR., Smith, DE.[2013]

References

1. England pubmed.ncbi.nlm.nih.gov

Bringing buprenorphine-naloxone detoxification to community treatment providers: the NIDA Clinical Trials Network field experience. [2022]

2. France pubmed.ncbi.nlm.nih.gov

Buprenorphine + naloxone: new combination. Opiate dependence: no proof of reduced risk of self-administered injection. [2013]

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

Buprenorphine maintenance: a new treatment for opioid dependence. [2019]

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

Buprenorphine alone or with naloxone: Which is safer? [2019]

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

Patients' perspectives on initiating treatment with extended-release naltrexone (XR-NTX). [2022]

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

Naltrexone Treatment for Pregnant Women With Opioid Use Disorder Compared With Matched Buprenorphine Control Subjects. [2020]

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

Innovative approaches to reduce unintended pregnancy and improve access to contraception among women who use opioids. [2023]

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

Subcutaneous Extended-Release Buprenorphine Use in Pregnancy. [2022]

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

Buprenorphine in the treatment of opiate dependence. [2013]