Locomotor Training + Testosterone for Spinal Cord Injury

Recruiting at 1 trial location

Overseen By Dana M Otzel, PhD

Age: 18+

Sex: Male

Trial Phase: Phase 2

Sponsor: North Florida Foundation for Research and Education

Must not be taking: Anticoagulants, Opioids, Glucocorticoids, others

Disqualifiers: Cancer, Cardiovascular events, Neurologic impairments, 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: 5

Duration: 6 months

21 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment for men with spinal cord injuries who have low testosterone and walking difficulties. It combines testosterone replacement therapy (a hormone treatment) with locomotor training, which includes treadmill and overground walking exercises. The goal is to determine if this combination can improve muscle size, bone health, and walking ability. Men with walking difficulties due to a spinal cord injury and symptoms of low testosterone, such as fatigue or decreased strength, might be suitable for this study. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group of participants.

Will I have to stop taking my current medications?

The trial requires that you stop taking certain medications before participating, such as testosterone replacement therapy, androgenic hormones, and certain bone medications. If you are on chronic opioids or glucocorticoids, you may continue them if they are for a chronic condition and expected to be used throughout the study.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that testosterone enanthate is generally safe for testosterone replacement therapy. One study found it increased muscle mass and improved bone health in men with spinal cord injuries, without major side effects, indicating it is usually well-tolerated in this group.

Studies have shown that locomotor training helps people with spinal cord injuries improve their walking ability. This common rehabilitation method is considered safe.

Overall, both treatments have been used in similar situations and are generally well-tolerated. However, as this is a Phase 2 trial, the researchers aim to learn more about how these treatments work together for this specific condition. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of locomotor training and testosterone enanthate for spinal cord injury because it offers a unique approach to rehabilitation. Unlike traditional treatments that often focus solely on physical therapy, this method combines treadmill and walking exercises with testosterone hormone therapy. Testosterone enanthate, administered via weekly injections, could enhance muscle growth and recovery, potentially leading to improved mobility and strength. By integrating hormone therapy with physical training, there's hope for more significant gains in motor function compared to standard physical therapy alone.

What evidence suggests that this trial's treatments could be effective for spinal cord injury?

Research has shown that testosterone enanthate, which participants in this trial may receive, may help prevent bone and muscle loss after a spinal cord injury (SCI). Animal studies have suggested it can increase muscle mass, potentially improving muscle strength and size in people. Locomotor training, another treatment option in this trial, has shown mixed results; some studies indicate it can improve walking ability after SCI, while others do not find a significant effect. This trial will also explore the combination of locomotor training with testosterone enanthate to potentially enhance muscle size and bone health, but more testing is needed to understand how well they work together. ^{1 3 6 7 8}

Who Is on the Research Team?

Joshua F Yarrow, PhD

Principal Investigator

North Florida/South Georgia Veterans Health System

Dana M Otzel, Phd

Principal Investigator

North Florida/South Georgia Veterans Health System

Are You a Good Fit for This Trial?

Men over 18 with low testosterone and spinal cord injury (SCI) causing walking difficulties are eligible. They must be medically stable, not seeking fertility, and willing to follow the treatment plan. Exclusions include major recent surgeries, other serious health conditions or cancers, certain cardiovascular issues, severe kidney disease, untreated sleep apnea, specific bone density scores below a threshold.

Inclusion Criteria

Documented approval from the study physician verifying medical status

Your testosterone levels are too low.

Medically-stable condition that is asymptomatic for conditions that will interfere with the study participation

Exclusion Criteria

Mental state that precludes understanding the study protocol

Major non-CV surgery (e.g., major abdominal or thoracic procedure) within 90-days prior to screening and/or a major surgery scheduled at the time of screening

Any other condition, therapy, lab abnormality, medical or psychiatric conditions, or reason that might pose a risk to the participant, make participation not in the person's best interest, confound the study results (e.g., inability to comply with study requirements), make the participant unsuitable to receive study intervention, or interfere with the person's ability to participate for the entire study duration

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive testosterone replacement therapy (TRT) with or without locomotor training (LT) for 6 months. TRT injections are given weekly, and LT involves 35 sessions of treadmill and overground walking during the initial 2-3 months.

6 months

Weekly visits for TRT injections, 4 sessions per week for LT during initial 2-3 months

Follow-up

Participants are monitored for safety and effectiveness after treatment, with assessments at 1-6 month intervals.

6 months

Assessments at 1, 3, and 6 months

What Are the Treatments Tested in This Trial?

Interventions

• Locomotor Training
• Testosterone Enanthate

Trial Overview The study tests whether combining testosterone replacement therapy (TRT) with locomotor training (treadmill and overground walking assistance) improves muscle size, bone density, and walking in men with SCI and low testosterone levels.

How Is the Trial Designed?

Group I: testosterone enanthate Experimental Treatment 1 Intervention

Testosterone enanthate via i.m. injection (100 mg/week)

Group II: locomotor training, testosterone enanthate Experimental Treatment 2 Interventions

Treadmill and overground walking training and testosterone enanthate via i.m. injection (100 mg/week)

Group III: non-interventional control Active Control 1 Intervention

Non-interventional control group

Locomotor Training is already approved in United States for the following indications:

Approved in United States as Locomotor Training for:

• Rehabilitation after spinal cord injury
• Improvement of muscle size and bone mineral density in men with low testosterone and ambulatory dysfunction

Who Is Running the Clinical Trial?

North Florida Foundation for Research and Education

Lead Sponsor

Trials

14

Recruited

860+

VA Eastern Colorado Health Care System

Collaborator

Trials

55

Recruited

26,200+

North Florida/South Georgia Veterans Health System

Collaborator

Trials

8

Recruited

2,000+

Brooks Rehabilitation

Collaborator

Trials

16

Recruited

1,900+

University of Florida

Collaborator

Trials

1,428

Recruited

987,000+

Published Research Related to This Trial

In a study involving 13 men with chronic complete spinal cord injury, the combination of testosterone treatment and resistance training (TT+RT) during a 16-week dose de-escalation period showed minimal effectiveness in preventing muscle size loss and changes in basal metabolic rate compared to a no-treatment group.

Despite the limited impact on muscle size and metabolism, the TT+RT group successfully maintained neuromuscular gains, indicating that this combined approach may help preserve strength even when reducing testosterone levels.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of dose de-escalation following testosterone treatment and evoked resistance exercise on body composition, metabolic profile, and neuromuscular parameters in persons with spinal cord injury. Gorgey, AS., Khalil, RE., Gill, R., et al.[2022]

In a study of 60 male veterans with chronic spinal cord injury, 43.3% were found to have testosterone deficiency, indicating a high prevalence of this condition in this population.

The study revealed that testosterone levels were significantly lower in individuals with more severe injuries (motor complete injuries) and in those using narcotic medications for pain management, suggesting that both injury severity and medication use are important factors to consider in testosterone deficiency assessments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prevalence of testosterone deficiency after spinal cord injury. Durga, A., Sepahpanah, F., Regozzi, M., et al.[2015]

Testosterone replacement therapy (TRT) in men with incomplete spinal cord injury (SCI) was associated with significantly higher motor function scores compared to a larger comparison group, suggesting potential benefits in strength and motor recovery.

No significant differences were found in functional independence measures (FIM) or motor scores for men with complete SCI, indicating that TRT may be more effective for those with some residual motor function.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Testosterone replacement therapy and motor function in men with spinal cord injury: a retrospective analysis. Clark, MJ., Petroski, GF., Mazurek, MO., et al.[2016]

Activity-based physical rehabilitation therapies (ABTs) can enhance neuromuscular recovery after spinal cord injury (SCI), but their effectiveness decreases with more severe injuries.

Combining testosterone treatment with ABTs may improve musculoskeletal recovery and neuroplasticity, as testosterone helps reduce muscle loss and supports motoneuron survival, suggesting a multimodal approach could be more effective than using either strategy alone.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Activity-Based Physical Rehabilitation with Adjuvant Testosterone to Promote Neuromuscular Recovery after Spinal Cord Injury. Otzel, DM., Lee, J., Ye, F., et al.[2018]

In a study involving two non-ambulatory participants with spinal cord injuries, both received locomotor training (LT) for two weeks, but increasing the frequency to four days a week did not yield additional benefits in muscle strength or metabolic profile compared to twice weekly sessions.

Both participants showed significant improvements in knee extensor muscle strength (28-34% increase) and a reduction in spasticity, indicating that even with less frequent training, LT can still enhance physical function in individuals with spinal cord injuries.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Acute effects of locomotor training on neuromuscular and metabolic profile after incomplete spinal cord injury. Gorgey, AS., Poarch, H., Harnish, C., et al.[2022]

In a study of 20 men with spinal cord injury, combining testosterone treatment with resistance training (TT + RT) showed potential to reverse or slow down bone loss, particularly in the proximal tibia, suggesting a promising rehabilitation strategy.

The TT + RT group exhibited greater improvements in intermuscular fascia length and some positive changes in bone microarchitecture, indicating that longer interventions may enhance bone quality after spinal cord injury.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bone and non-contractile soft tissue changes following open kinetic chain resistance training and testosterone treatment in spinal cord injury: an exploratory study. Holman, ME., Chang, G., Ghatas, MP., et al.[2021]

Short-term bodyweight-supported treadmill training (TM) did not prevent bone loss or muscle atrophy in rats after spinal cord injury (SCI), indicating that this intervention alone is insufficient for musculoskeletal recovery.

In contrast, combining testosterone enanthate (TE) with TM led to significant improvements in bone preservation, muscle maintenance, and locomotor recovery, with 75% of treated rats regaining voluntary hindlimb stepping, highlighting the enhanced efficacy of this combined approach.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Locomotor training with adjuvant testosterone preserves cancellous bone and promotes muscle plasticity in male rats after severe spinal cord injury. Yarrow, JF., Kok, HJ., Phillips, EG., et al.[2021]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11848707

Locomotor training for walking after spinal cord injury - PMC Locomotor training for walking is therefore used in rehabilitation after SCI and might help to improve a person's ability to walk. However, a systematic review ...

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/18827681/

Locomotor training for walking after spinal cord injury Overall, the results were inconclusive. There was no statistically significant effect of locomotor training on walking function after SCI ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT00006429

NCT00006429 | Treadmill Training for Spinal Cord Injury The primary outcome measures are the level of independence for ambulation and the maximal speed for walking 50 feet. Patients will be tested by masked examiners ...

4. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0003999313005157

Effects of Locomotor Training After Incomplete Spinal Cord ... This systematic review aimed to provide an overview of the current evidence on locomotor training approaches for gait rehabilitation after incomplete SCI.

5. jneuroengrehab.biomedcentral.com jneuroengrehab.biomedcentral.com/articles/10.1186/s12984-023-01134-7

Cost-effectiveness analysis of overground robotic training ... Overground robotic training was more effective and cost more than conventional training for people with complete SCI. The incremental cost ...

6. mayoclinic.org mayoclinic.org/tests-procedures/locomotor-training-for-spinal-cord-injury/about/pac-20394608

Locomotor training for spinal cord injury Locomotor training is a type of therapy that can help people with spinal cord injury improve or recover their ability to walk.

7. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0003999317312856

Longitudinal Recovery and Reduced Costs After 120 ... Delivering at least 120 sessions of LT improves recovery from incomplete chronic SCI. Because walking reduces rehospitalization, LT delivered beyond the average ...

8. academic.oup.com academic.oup.com/ptj/article/85/12/1356/2805094

Locomotor Training Progression and Outcomes After ... Outcomes. Walking speed and independence improved from 0.19 m/s as a home ambulator using a rolling walker and a right ankle-foot orthosis to ...