Opioid Antagonist Therapy for Low Testosterone

Overseen By Study Coordinator

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Stephanie B. Seminara, MD

Must not be taking: Hormonal replacements, Opioid pathway drugs

Disqualifiers: Illicit drug use, Excessive alcohol, others

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

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

Compensation: Varies

Number of Visits: 2

23 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial uses hormone injections and naloxone to study their effects on people with low reproductive hormone levels due to an unknown cause. Kisspeptin and GnRH help increase hormone production, while naloxone blocks opioid effects. The goal is to understand how these treatments affect hormone levels in these patients.

Will I have to stop taking my current medications?

The trial requires that you stop taking any medications that can affect the reproductive system or the opioid pathway. If you're on such medications, you must be willing to go through a washout period (time without taking these medications) before participating.

What data supports the effectiveness of the drug combination used in the clinical trial for low testosterone?

Research shows that naloxone, an opioid antagonist, can influence hormone levels by increasing luteinizing hormone (LH) secretion, which is important for testosterone production. Additionally, kisspeptin has been shown to stimulate the reproductive hormone axis, suggesting that these components may help regulate testosterone levels. ^{1 2 3 4 5}

Is opioid antagonist therapy, like naloxone, safe for humans?

Naloxone, an opioid antagonist, has been studied in humans and generally shows no significant adverse effects on hormone levels, suggesting it is safe for use in humans. ^{2 3 5 6 7}

How does the treatment for low testosterone using kisspeptin and GnRH differ from other treatments?

This treatment is unique because it targets the kisspeptin-GPR54 system, which plays a crucial role in stimulating the reproductive hormone pathway, unlike traditional therapies that may not address this specific mechanism. By using kisspeptin to stimulate GnRH (a hormone that triggers testosterone production), this approach could offer a novel way to manage low testosterone levels. ^{1 5 8 9 10}

Research Team

Stephanie B. Seminara, MD

Principal Investigator

Massachusetts General Hospital

Eligibility Criteria

This trial is for adults with low testosterone or estradiol due to hypogonadotropic hypogonadism (HH), who are not currently seeking fertility, and have stable medical conditions. Participants should not be on medications affecting reproductive functions, have no history of severe medication reactions, and must pass certain blood tests.

Inclusion Criteria

I can stop my hormone therapy for a certain period if needed.

Women must have a negative pregnancy test before joining the study, and another test may be done before taking the medication.

I haven't taken drugs affecting my hormones except for treating my reproductive condition.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Period 1

Participants undergo q10 min blood sampling for up to 12 hours without medication

1 day

1 visit (in-person)

Period 2

Participants undergo q10 min blood sampling for up to 12 hours with naloxone bolus and infusion

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

2-4 weeks

Treatment Details

Interventions

• GnRH
• Kisspeptin, GnRH
• Naloxone

Trial Overview The study is testing the impact of opioid antagonists like naloxone on the hormonal axis in people with idiopathic HH. It aims to understand how blocking opioids affects hormones that control reproductive functions using substances such as kisspeptin and GnRH.

Participant Groups

Group I: naloxone 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.)

Who Is Running the Clinical Trial?

Stephanie B. Seminara, MD

Lead Sponsor

Trials

10

Recruited

840+

Findings from Research

Kisspeptin plays a crucial role in regulating reproductive functions by controlling the release of GnRH, but its therapeutic use is limited due to its susceptibility to degradation.

Investigational kisspeptin analogs have shown promise in clinical studies, causing initial increases in gonadotropin and testosterone levels, although these effects diminish over time, indicating a need for further research on their long-term efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects and therapeutic potentials of kisspeptin analogs: regulation of the hypothalamic-pituitary-gonadal axis. Matsui, H., Asami, T.[2022]

References

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

Evidence that down regulation of hypothalamic KiSS-1 expression is involved in the negative feedback action of testosterone to regulate luteinising hormone secretion in the adult male rhesus monkey (Macaca mulatta). [2018]

2. Germany pubmed.ncbi.nlm.nih.gov

Effects of naloxone on gonadotropin secretion in Klinefelter syndrome. [2019]

3. Iran pubmed.ncbi.nlm.nih.gov

Morphine attenuates testosterone response to central injection of kisspeptin in male rats. [2021]

4. Switzerland pubmed.ncbi.nlm.nih.gov

Hypothalamic Response to Kisspeptin-54 and Pituitary Response to Gonadotropin-Releasing Hormone Are Preserved in Healthy Older Men. [2021]

5. Poland pubmed.ncbi.nlm.nih.gov

[Effect of blockade of opiate receptors by naloxone on lutropin (LH), follitropin (FSH) and testosterone secretion in patients after kidney transplantation]. [2018]

6. Switzerland pubmed.ncbi.nlm.nih.gov

Effects and therapeutic potentials of kisspeptin analogs: regulation of the hypothalamic-pituitary-gonadal axis. [2022]

7. Denmark pubmed.ncbi.nlm.nih.gov

Naloxone administration does not affect gonadotropin secretion in patients with Klinefelter's syndrome. [2019]

8. Netherlands pubmed.ncbi.nlm.nih.gov

Interactions of morphine and Peptide 234 on mean plasma testosterone concentration. [2022]

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

Kisspeptin antagonists. [2017]

10. Iran pubmed.ncbi.nlm.nih.gov

Morphine and kisspeptin influences on 5-α reductase and aromatase gene expression in adult male rats. [2022]