Testosterone Therapy for Low Testosterone

(PATH Trial)

Overseen By Anna Goldman, MD

Age: 18+

Sex: Male

Trial Phase: Phase 2

Sponsor: Brigham and Women's Hospital

Must be taking: Opioid analgesics

Must not be taking: Testosterone

Disqualifiers: Prostate cancer, Organic hypogonadism, Bipolar, others

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

Compensation: Varies

Number of Visits: 3

Duration: 6 months

150 Participants Needed

Trial Summary

What is the purpose of this trial?

The aim of this trial is to evaluate whether testosterone replacement results in greater improvement in pain perception, pain tolerance, sexual function, fatigue, and quality of life when compared with placebo in men with chronic spinal pain treated with opioids who have opioid-induced hypogonadism (low testosterone).

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, you must not have used testosterone in the past 6 months.

What data supports the effectiveness of the drug Testosterone undecanoate for low testosterone?

Research shows that Testosterone undecanoate is effective in treating male hypogonadism (a condition where the body doesn't produce enough testosterone) by significantly increasing plasma testosterone levels, improving symptoms like decreased energy and libido, and providing a convenient oral option that may enhance patient compliance. ^{1 2 3 4 5}

Is testosterone therapy generally safe for humans?

Testosterone therapy, particularly with testosterone undecanoate, has been shown to have a good safety profile in humans. Long-term studies indicate no significant adverse effects on liver function, lipid profiles, or prostate health, and it avoids the 'roller coaster' effects of traditional testosterone injections. ^{1 4 5 6 7}

What makes testosterone cypionate and testosterone undecanoate unique for treating low testosterone?

Testosterone cypionate and testosterone undecanoate are unique because they offer different administration routes and dosing schedules compared to other testosterone therapies. Testosterone cypionate is typically injected every 1-2 weeks, while testosterone undecanoate can be administered less frequently, potentially improving convenience and adherence for patients. ^{8 9 10 11 12}

Research Team

Robert R Edwards, PhD

Principal Investigator

Brigham and Women's Hospital

Shehzad Basaria, MD

Principal Investigator

Brigham and Women's Hospital

Eligibility Criteria

This trial is for men over 18 with chronic back pain treated with opioids, leading to low testosterone levels. They must have been on opioid painkillers for at least six months and be willing to consent. Men with prostate or breast cancer, certain mental health conditions, recent heart issues, severe kidney or liver disease, or specific metallic implants cannot participate.

Inclusion Criteria

I have been using opioid painkillers for at least 6 months.

Ability and willingness to provide informed consent

I have long-term back pain not caused by cancer.

Exclusion Criteria

I have not used testosterone in the last 6 months.

Your blood has more red blood cells than it should.

Your prostate-specific antigen (PSA) level is higher than 4 ng/mL if you are Caucasian, or higher than 3 ng/mL if you are African-American.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive testosterone or placebo for 6 months to evaluate improvements in pain perception, sexual function, fatigue, and quality of life

6 months

Baseline, 3 months, and 6 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Placebo
• Testosterone cypionate
• Testosterone Undecanoate 250 MG/ML

Trial Overview The study tests if testosterone replacement (Testosterone Undecanoate) can better improve pain perception, tolerance, sexual function, fatigue and life quality compared to a placebo in these men.

Participant Groups

Group I: Testosterone Experimental Treatment 1 Intervention

Intramuscular injections of testosterone undecanoate 750 mg.

Group II: Placebo Placebo Group 1 Intervention

Intramuscular injections of placebo.

Testosterone cypionate is already approved in United States for the following indications:

Approved in United States as Depo-Testosterone for:

• Primary hypogonadism
• Hypogonadotropic hypogonadism
• Delayed puberty

Who Is Running the Clinical Trial?

Brigham and Women's Hospital

Lead Sponsor

Trials

1,694

Recruited

14,790,000+

Findings from Research

Testosterone undecanoate (TU) is a long-acting injectable testosterone replacement therapy that can be administered only four times a year, providing stable testosterone levels with an excellent safety profile.

Long-term studies, including data from patients treated for over 8 years, show that TU is effective and safe, with no serious side effects reported, making it a desirable option for hypogonadal men.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Testosterone undecanoate in the treatment of male hypogonadism. Edelstein, D., Basaria, S.[2014]

Testosterone therapy (TT) can effectively alleviate symptoms of testosterone deficiency, such as low energy and libido, by restoring serum testosterone levels to the normal range.

Testosterone undecanoate (TU), available in both oral and injectable forms, offers a convenient option for patients, potentially improving compliance, while injectable forms remain the most cost-effective initial treatment for most patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety Aspects and Rational Use of Testosterone Undecanoate in the Treatment of Testosterone Deficiency: Clinical Insights. Campbell, K., Muthigi, A., Ghomeshi, A., et al.[2023]

Male hypogonadism affects a significant portion of the male population (10-30%) and is often not adequately recognized or treated, highlighting the need for effective treatment options.

JATENZO and TLANDO are the first oral testosterone formulations approved by the FDA, utilizing a unique delivery system that allows for safe absorption without causing liver dysfunction, addressing limitations of traditional testosterone replacement therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Testosterone Replacement Therapy: A Narrative Review with a Focus on New Oral Formulations. Bhat, SZ., Dobs, AS.[2023]

In a 24-month study involving 69 hypogonadal men, oral testosterone undecanoate (TU) significantly increased total testosterone levels into the normal range and improved sexual function across multiple domains, indicating its efficacy as a testosterone replacement therapy.

The treatment was found to be safe, with no significant adverse effects on liver function or prostate health, although there were minor increases in blood pressure and hematocrit levels, which remained within acceptable limits.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Two-Year Analysis of a New Oral Testosterone Undecanoate (TU) Formulation in Hypogonadal Men: Efficacy, Impact on Psychosexual Function, and Safety. Honig, S., Gittelman, M., Kaminetsky, J., et al.[2023]

In a study involving 76 hypogonadal males, testosterone undecanoate administered orally for 9 weeks was effective in 60 out of 66 patients who completed the trial, indicating its efficacy in treating male hypogonadism.

The treatment led to a significant increase in plasma testosterone levels, with a positive correlation between plasma testosterone and testosterone undecanoate levels, although some patients experienced gastrointestinal side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical efficacy of testosterone undecanoate in male hypogonadism. Maisey, NM., Bingham, J., Marks, V., et al.[2019]

Testosterone undecanoate offers a more stable and effective treatment for androgen deficiency compared to traditional injectable testosterone, with injections spaced 12 weeks apart after an initial loading phase, maintaining plasma testosterone levels within the normal range.

This new formulation has an excellent safety profile, showing no adverse effects on blood parameters, lipid profiles, or prostate health, while effectively reversing symptoms of hypogonadism in bone, muscle, and sexual function.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Testosterone depot injection in male hypogonadism: a critical appraisal. Yassin, AA., Haffejee, M.[2021]

Testosterone undecanoate (Andriol) has been shown to be a safe oral androgen for hypogonadal men, with no significant changes in liver function over a minimum follow-up period of 10 years for 33 participants.

Serum testosterone and 5 alpha-dihydrotestosterone levels remained stable throughout the study, and no signs of prostate tumors were found, suggesting that long-term use does not pose significant risks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A ten-year safety study of the oral androgen testosterone undecanoate. Gooren, LJ.[2014]

In a study of 91 rheumatoid arthritis patients who achieved stable low disease activity on etanercept and methotrexate, continuing etanercept treatment (either at full or reduced dose) significantly reduced the risk of disease flare compared to a placebo after 48 weeks.

Patients receiving the full dose of etanercept (50 mg) had a median time to flare of 48 weeks, while those on a reduced dose (25 mg) had 36 weeks, compared to just 6 weeks for the placebo group, indicating that maintaining or reducing etanercept dosage can effectively manage rheumatoid arthritis symptoms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Full dose, reduced dose or discontinuation of etanercept in rheumatoid arthritis. van Vollenhoven, RF., Østergaard, M., Leirisalo-Repo, M., et al.[2022]

In a study of 314 patients with early rheumatoid arthritis, achieving an optimal methotrexate (MTX) dose (≥10 mg/week initially, escalating to ≥20 mg/week) significantly improved the chances of reaching remission and normal functioning after one year, with odds ratios of 4.28 and 4.36, respectively.

Despite the benefits in symptoms and function, the optimal MTX dose did not affect radiological progression of the disease over the two-year study period.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Optimal methotrexate dose is associated with better clinical outcomes than non-optimal dose in daily practice: results from the ESPOIR early arthritis cohort. Gaujoux-Viala, C., Rincheval, N., Dougados, M., et al.[2022]

Biological treatments are recommended for children with polyarticular course Juvenile Idiopathic Arthritis (JIA) who have active disease and do not respond to methotrexate after 3 to 6 months, ensuring a structured approach to treatment.

Before starting biological therapy, children must be screened for latent tuberculosis, and treatment should be reconsidered if there is no improvement in JIA symptoms after two consecutive visits three months apart.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Guidelines for prescribing and monitoring biologic therapies in juvenile idiopathic arthritis]. Santos, MJ., Fonseca, JE., Canhão, H., et al.[2013]

Methotrexate is recognized as the most effective and safest disease-modifying anti-rheumatic drug (DMARD) for rheumatoid arthritis (RA), with over 80% of patients starting treatment with it, indicating its long-term effectiveness.

While biological agents can be more effective for patients with severe RA, the best outcomes are achieved when these agents are combined with methotrexate, reinforcing methotrexate's role as the primary treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Methotrexate as the "anchor drug" for the treatment of early rheumatoid arthritis. Pincus, T., Yazici, Y., Sokka, T., et al.[2022]

Methotrexate (MTX) shows a delayed therapeutic response in rheumatoid arthritis (RA), with maximum improvement in disability scores occurring around 30 months after starting treatment, indicating that patients may need to be on MTX for a longer period to see full benefits.

Despite initial improvements, disability scores began to re-progress after 42 months, suggesting that treatment strategies should be adjusted sooner to prevent return to baseline disability, highlighting the need for more proactive management of RA with potential dosage adjustments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The methotrexate therapeutic response in rheumatoid arthritis. Ortendahl, M., Holmes, T., Schettler, JD., et al.[2013]

References

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

Testosterone undecanoate in the treatment of male hypogonadism. [2014]

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

Safety Aspects and Rational Use of Testosterone Undecanoate in the Treatment of Testosterone Deficiency: Clinical Insights. [2023]

3. England pubmed.ncbi.nlm.nih.gov

Testosterone Replacement Therapy: A Narrative Review with a Focus on New Oral Formulations. [2023]

4. Netherlands pubmed.ncbi.nlm.nih.gov

Two-Year Analysis of a New Oral Testosterone Undecanoate (TU) Formulation in Hypogonadal Men: Efficacy, Impact on Psychosexual Function, and Safety. [2023]

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

Clinical efficacy of testosterone undecanoate in male hypogonadism. [2019]

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

Testosterone depot injection in male hypogonadism: a critical appraisal. [2021]

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

A ten-year safety study of the oral androgen testosterone undecanoate. [2014]

8. England pubmed.ncbi.nlm.nih.gov

Full dose, reduced dose or discontinuation of etanercept in rheumatoid arthritis. [2022]

9. England pubmed.ncbi.nlm.nih.gov

Optimal methotrexate dose is associated with better clinical outcomes than non-optimal dose in daily practice: results from the ESPOIR early arthritis cohort. [2022]

10. Portugal pubmed.ncbi.nlm.nih.gov

[Guidelines for prescribing and monitoring biologic therapies in juvenile idiopathic arthritis]. [2013]

11. Italy pubmed.ncbi.nlm.nih.gov

Methotrexate as the "anchor drug" for the treatment of early rheumatoid arthritis. [2022]

12. Canada pubmed.ncbi.nlm.nih.gov

The methotrexate therapeutic response in rheumatoid arthritis. [2013]