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 pilot study will determine the feasibility of implementing a combinatory rehabilitation strategy involving testosterone replacement therapy (TRT) with locomotor training (LT; walking on a treadmill with assistance and overground walking) in men with testosterone deficiency and walking dysfunction after incomplete or complete spinal cord injury. The investigators hypothesize that LT+TRT treatment will improve muscle size and bone mineral density in men with low T and ambulatory dysfunction after incomplete or complete SCI, along with muscle fundtion and walking recovery in men with T low and ambulatory dysfunction ater incomplete SCI.

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 the combination of locomotor training and testosterone safe for humans?

Research on the combination of locomotor training and testosterone in humans with spinal cord injury suggests it may be safe, as studies have not reported significant adverse effects. However, most safety data comes from studies on animals or related therapies, so more human-specific research is needed to confirm safety. ^{1 2 3 4 5}

How does the treatment of Locomotor Training with Testosterone Enanthate differ from other treatments for spinal cord injury?

This treatment combines locomotor training (walking therapy) with testosterone enanthate, which together help preserve bone and muscle health and improve walking ability after spinal cord injury. Unlike other treatments, this combination offers more comprehensive benefits by enhancing both musculoskeletal recovery and neuromuscular function, which are not achieved by either component alone. ^{1 2 3 4 6}

What data supports the effectiveness of the treatment Locomotor Training + Testosterone for Spinal Cord Injury?

Research suggests that combining testosterone with physical rehabilitation therapies like locomotor training may improve muscle and nerve recovery in people with spinal cord injuries. Testosterone can help reduce muscle loss and support nerve health, while locomotor training can enhance walking ability. ^{2 4 5 6 7}

Who Is on the Research Team?

Dana M Otzel, Phd

Principal Investigator

North Florida/South Georgia Veterans Health System

Joshua F Yarrow, 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

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 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]

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 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]

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]

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]

Citations

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

Testosterone replacement therapy and motor function in men with spinal cord injury: a retrospective analysis. [2016]

2. Switzerland pubmed.ncbi.nlm.nih.gov

Activity-Based Physical Rehabilitation with Adjuvant Testosterone to Promote Neuromuscular Recovery after Spinal Cord Injury. [2018]

3. England 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. [2021]

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

Acute effects of locomotor training on neuromuscular and metabolic profile after incomplete spinal cord injury. [2022]

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

Prevalence of testosterone deficiency after spinal cord injury. [2015]

6. United States 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. [2021]

7. United States 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. [2022]