Testosterone Nasal Gel for Spinal Cord Injury

Overseen By Noam Y Harel, MD PhD

Age: 18+

Sex: Male

Trial Phase: Phase < 1

Sponsor: VA Office of Research and Development

Must not be taking: Amphetamines, Neuroleptics, others

Disqualifiers: Seizures, Ventilator dependence, others

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 1

Duration: 1 day

15 Participants Needed

Trial Summary

What is the purpose of this trial?

Spinal cord injury (SCI) disrupts the nerves controlling movement, along with those that regulate functions like heart rate and blood pressure (known as the autonomic nervous system, or ANS). Testosterone (T) plays a significant role in brain health and ANS reflex function in non-neurologically impaired men. However, little is known about the relationships between T, nerve function, and ANS dysfunction after SCI. Interestingly, up to 60% of men with SCI exhibit persistently low T concentrations, which may worsen nerve and ANS dysfunction. In uninjured eugonadal people (normal physiologic range of serum T concentrations), a single pharmacologic dose of intranasal T has been shown to quickly improve nerve function, but no study has evaluated if T administration alters nerve and ANS function in men with SCI. Herein, the investigators will conduct the first study to test how a single dose of intranasal T impacts motor and ANS function in this population.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you must have a stable prescription medication regimen for at least 30 days before joining. You cannot be on treatment for low testosterone or use medications that lower the seizure threshold.

Is testosterone nasal gel safe for humans?

Testosterone nasal gel, known as Natesto, has been used to treat low testosterone levels in men, but the FDA has warned against its use for age-related low testosterone due to safety concerns. It is generally applied in the nose and has been studied in people with allergies, but specific safety data for spinal cord injury is not available. ^{1 2 3 4 5}

How is the drug Natesto different from other treatments for spinal cord injury?

Natesto is unique because it is a testosterone gel applied inside the nose, which is different from other testosterone treatments that are usually injected or applied to the skin. This nasal application allows for more frequent dosing, which might help maintain more stable testosterone levels. ^{1 2 3 4 5}

Research Team

Jacob A Goldsmith, PhD

Principal Investigator

James J. Peters Veterans Affairs Medical Center

Eligibility Criteria

This trial is for men aged 18-80 with spinal cord injury (SCI), either traumatic or non-traumatic, who have stable medication use and are not on testosterone treatment. They must be at least a year post-injury and able to commit to three study visits in a month.

Inclusion Criteria

My medication has not changed in the last 30 days.

I am not on medication for low testosterone.

Time since injury (TSI) more than 12 months

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive a single dose of intranasal testosterone replacement therapy (TRT) or placebo to assess neurophysiological and cardiovagal responses

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, including electromyographic responses and cardiovagal function

up to 1 day

Treatment Details

Interventions

• Natesto testosterone intranasal gel

Trial Overview The study examines the effects of Natesto, an intranasal testosterone gel, on nerve and autonomic nervous system function in men with SCI. It compares these effects against Ayr Saline Nasal Gel, which does not contain hormones.

Participant Groups

Group I: Intranasal TRT Active Control 1 Intervention

Participant-blinded (11 mg of Natesto)

Group II: Placebo Placebo Group 1 Intervention

Participant-blinded (Ayr Saline Gel)

Natesto testosterone intranasal gel is already approved in United States, Canada for the following indications:

Approved in United States as Natesto for:

• Hypogonadism

Approved in Canada as Natesto for:

• Hypogonadism

Who Is Running the Clinical Trial?

VA Office of Research and Development

Lead Sponsor

Trials

1,691

Recruited

3,759,000+

Findings from Research

In a study of 117 hypogonadal men (24 TTh-naive and 93 TTh-experienced) over 120 days, the testosterone nasal gel (Natesto®) significantly improved symptoms and patient satisfaction compared to previous topical testosterone treatments.

Patients reported a 15% improvement in symptoms and a 30% increase in convenience with Natesto®, with 67.2% preferring it over topical options, suggesting that its ease of use may enhance treatment compliance.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The My-T study: Patient satisfaction and preference comparing topical and nasal testosterone therapies. Lee, J., Brock, G., Barkin, J., et al.[2022]

In a study of hypogonadal males treated with testosterone nasal gel (TNG) for 90 days, 77% of patients achieved normal testosterone levels, indicating the efficacy of TNG in managing testosterone deficiency.

The study highlighted that while many patients were up-titrated to a higher dose based on physician assessments, there was no significant improvement in symptom scores at the higher dose, suggesting that initial dosing based on symptoms may be sufficient for effective treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

MY-T study: Symptom-based titration decisions when using testosterone nasal gel, Natesto&#174;. Lee, J., Brock, G., Barkin, J., et al.[2022]

The pharmacokinetics of testosterone nasal gel (TNG) show that allergic rhinitis (AR) does not affect the absorption of testosterone, indicating that TNG can be safely used in patients with AR.

In a large phase 3 study involving 306 hypogonadal patients, treatment outcomes with TNG were similar for both AR and non-AR patients, suggesting that AR history does not impact the effectiveness or safety of TNG over long-term use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase 1 pharmacokinetics and phase 3 efficacy of testosterone nasal gel in subjects with seasonal allergies. Rogol, AD., Tkachenko, N., Badorrek, P., et al.[2022]

Natesto nasal gel, administered three times daily, effectively raises low testosterone levels to the normal range in patients with hypogonadism, offering a potential alternative to traditional testosterone treatments.

The FDA has cautioned against using testosterone therapy solely for age-related hypogonadism due to safety concerns and insufficient evidence of benefit in older men.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Testosterone nasal gel (Natesto) for hypogonadism. [2015]

In a study of 60 men with symptomatic hypogonadism, 90.9% achieved normal testosterone levels after 6 months of treatment with 4.5% nasal testosterone gel (Natesto), indicating its efficacy in raising testosterone levels.

The treatment maintained normal sperm counts in 93.9% of participants at 6 months, suggesting that Natesto is a safe option for men with hypogonadism who want to preserve their fertility.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of Natesto on Reproductive Hormones, Semen Parameters and Hypogonadal Symptoms: A Single Center, Open Label, Single Arm Trial. Ramasamy, R., Masterson, TA., Best, JC., et al.[2021]

References

1. Canada pubmed.ncbi.nlm.nih.gov

The My-T study: Patient satisfaction and preference comparing topical and nasal testosterone therapies. [2022]

2. Canada pubmed.ncbi.nlm.nih.gov

MY-T study: Symptom-based titration decisions when using testosterone nasal gel, Natesto&#174;. [2022]

3. Canada pubmed.ncbi.nlm.nih.gov

Phase 1 pharmacokinetics and phase 3 efficacy of testosterone nasal gel in subjects with seasonal allergies. [2022]

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

Testosterone nasal gel (Natesto) for hypogonadism. [2015]

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

Effect of Natesto on Reproductive Hormones, Semen Parameters and Hypogonadal Symptoms: A Single Center, Open Label, Single Arm Trial. [2021]