Testosterone + Hybrid Exercise for Spinal Cord Injury

Overseen By Nancy Latham, PhD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Brigham and Women's Hospital

Must be taking: Androgens

Must not be taking: Testosterone, Anabolic therapies, Blood thinners

Disqualifiers: Cancer, Psychosis, Dementia, MI, Stroke, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 16 weeks

84 Participants Needed

Trial Summary

What is the purpose of this trial?

The proposed phase 2 trial a randomized, placebo-controlled, parallel group trial in persons with cervical or thoracic SCI, AIS grade A, B, C, or D, 6 months or later after injury. The trial will test the hypothesis that a Home-Based Multimodality Functional Recovery and Metabolic Health Enhancement Program that addresses multiple pathophysiologic factors in SCI and includes functional electrical stimulation during leg cycling (FES-LC) plus arm ergometry and an androgen will be more efficacious than functional electrical stimulation during leg cycling (FES-LC) plus arm ergometry plus placebo in improving aerobic capacity, function, metabolism, bone health, and wellbeing.

Do I have to stop taking my current medications for the trial?

The trial protocol does not specify if you must stop taking your current medications. However, you cannot participate if you are using testosterone or other anabolic therapies, or if you are on certain blood thinners like Coumadin, heparin, or rivaroxaban. Please consult with the trial coordinators for more details.

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 cannot participate if you have used testosterone or similar therapies in the last 6 months, or if you are on certain blood thinners like Coumadin or heparin.

What data supports the idea that Testosterone + Hybrid Exercise for Spinal Cord Injury is an effective treatment?

The available research shows that combining testosterone with hybrid exercise, which includes functional electrical stimulation (FES) and arm cycling, can improve motor function and physical fitness in individuals with spinal cord injury. Studies indicate that this treatment can increase muscle strength, endurance, and muscle size. Participants in these studies were able to perform more work during exercise, suggesting improved physical capabilities. Additionally, the treatment was shown to enhance aerobic metabolism, which is how the body uses oxygen to produce energy, indicating better overall fitness. ^{1 2 3 4 5}

What data supports the effectiveness of the treatment Hybrid Exercise, Functional Electrical Stimulation during Leg Cycling (FES-LC) plus Arm Ergometry, and Testosterone Undecanoate for spinal cord injury?

Research shows that testosterone replacement therapy can improve motor function in men with spinal cord injury, and functional electrical stimulation (FES) cycling can enhance muscle strength, endurance, and overall fitness in individuals with spinal cord injury. ^{1 2 3 4 5}

What safety data exists for the treatment involving testosterone and hybrid exercise for spinal cord injury?

The safety data for hybrid exercise involving Functional Electrical Stimulation (FES) in spinal cord injury patients is explored in several studies. One study assessed the safety and feasibility of Hybrid High-Intensity Interval Training using FES leg cycling and arm ski ergometer, indicating it is feasible and safe. Another study examined the safety and acceptability of FES-assisted rowing, finding it safe and acceptable. However, specific safety data for the combination of testosterone treatment (Testosterone Undecanoate, Nebido, Aveed) with hybrid exercise is not directly addressed in the provided research abstracts. ^{3 4 6 7 8}

Is the combination of testosterone and hybrid exercise safe for people with spinal cord injuries?

Research on hybrid exercise, which includes functional electrical stimulation (FES) for people with spinal cord injuries, suggests it is generally safe and feasible. However, specific safety data on combining this exercise with testosterone treatment is not provided in the available studies. ^{3 4 6 7 8}

Is the treatment Hybrid Exercise a promising treatment for spinal cord injury?

Yes, Hybrid Exercise, which combines arm and leg cycling with electrical stimulation, shows promise for people with spinal cord injury. It can help improve physical recovery, increase independence, and support better health outcomes. ^{3 4 5 9 10}

How is the Hybrid Exercise treatment for spinal cord injury different from other treatments?

The Hybrid Exercise treatment combines functional electrical stimulation (FES) with leg cycling and arm ergometry, which is unique because it simultaneously engages both the arms and legs, potentially enhancing physical recovery and functional independence in individuals with spinal cord injury. ^{3 4 5 9 10}

Research Team

Shalender Bhasin, MD

Principal Investigator

Brigham and Women's Hospital

Eligibility Criteria

This trial is for men and women aged 19-70 with spinal cord injury (SCI), at least 6 months post-injury, who primarily use a wheelchair. Participants must be medically stable, able to follow directions, and if female and of reproductive potential, agree to use effective contraception during the study.

Inclusion Criteria

For females of reproductive potential who are sexually active: use of highly effective contraception for at least 1 month prior to Day 1 and agreement to use such a method during study participation and for an additional 12 weeks after the end of intervention

I am between 19 and 70 years old.

I am medically stable and can follow instructions.

Exclusion Criteria

You are currently doing a regular exercise program and are not willing to stop it for the study.

My PSA level is above 4 ng/ml, or above 3 ng/ml due to my high risk of prostate cancer.

Your liver enzymes ALT and AST are more than three times the normal level.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

14 weeks

Baseline Studies and Day 1

Baseline assessments and initial setup for the intervention

1 week

Treatment

Participants receive the multimodality intervention or placebo for 16 weeks

16 weeks

Regular home-based sessions with periodic in-person or nurse visits

End of Study Assessments

Final assessments to evaluate the outcomes of the intervention

Up to 3 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Hybrid Exercise
• Testosterone Undecanoate

Trial Overview The trial tests a Home-Based Multimodality Program combining functional electrical stimulation leg cycling with arm ergometry and testosterone against the same exercise program with a placebo. It aims to improve aerobic capacity, function, metabolism, bone health, and wellbeing in SCI patients.

Participant Groups

Group I: Multi-modality intervention group Experimental Treatment 2 Interventions

Hybrid exercise (functional electrical stimulation - leg cycling, FES LC plus arm ergometry) plus Testosterone undecanoate

Group II: Placebo group Placebo Group 1 Intervention

Hybrid exercise plus placebo medication

Who Is Running the Clinical Trial?

Brigham and Women's Hospital

Lead Sponsor

Trials

1,694

Recruited

14,790,000+

Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

Collaborator

Trials

2,103

Recruited

2,760,000+

Spaulding Rehabilitation Hospital

Collaborator

Trials

143

Recruited

11,200+

Findings from Research

A study involving 30 subjects with spinal cord injury demonstrated that functional electrical stimulation (FES) exercise programs safely improved lower extremity muscle strength, endurance, and bulk.

Participants showed enhanced aerobic metabolism and increased muscle density, indicating that FES can effectively reverse some degenerative changes associated with spinal cord injury.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Physiologic effects of functional electrical stimulation-induced exercises in spinal cord-injured individuals. Ragnarsson, KT.[2007]

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]

In a study involving nine male participants with spinal cord injuries, combined arm and leg exercise (HYBRID) resulted in significantly higher oxygen uptake (V˙O2peak) and cardiovascular responses compared to arm cycling alone (ACE) and FES-assisted leg cycling (FES-LCE).

FES-LCE alone produced lower oxygen uptake and cardiovascular metrics, indicating it may not be sufficient for improving aerobic fitness in individuals with spinal cord injuries, suggesting that incorporating combined exercises could enhance fitness outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Exercise responses during functional electrical stimulation cycling in individuals with spinal cord injury. Hasnan, N., Ektas, N., Tanhoffer, AI., et al.[2013]

A 3-month training program using functional electrical stimulation leg cycle ergometry (FES-LCE) significantly improved small artery compliance by 63% in four women with spinal cord injury (SCI).

However, there was no significant change in large artery compliance after the FES-LCE training, indicating that the benefits of this intervention may be more pronounced in smaller arteries.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The effects of functional electrical stimulation leg cycle ergometry training on arterial compliance in individuals with spinal cord injury. Zbogar, D., Eng, JJ., Krassioukov, AV., et al.[2021]

In a study involving 15 patients with chronic spinal cord injury, functional electrical stimulation (FES) cycling for 6 weeks significantly improved functional independence and mobility, as indicated by better scores on the Functional Independence Measure (FIM) and improved performance in walking tests.

FES cycling also led to a notable increase in forced vital capacity (FVC), suggesting benefits for pulmonary function, while biochemical values did not show significant changes, indicating that FES cycling is a safe and effective rehabilitation intervention for patients with spinal cord injuries.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Functional electrical stimulation cycling in patients with chronic spinal cord injury: a pilot study. Gurcay, E., Karaahmet, OZ., Cankurtaran, D., et al.[2022]

Hybrid High-Intensity Interval Training (HIIT) using Functional Electrical Stimulation (FES) was found to be safe and well-accepted by participants with spinal cord injuries, with no serious adverse events reported during the 8-week study involving 8 participants.

Participants experienced a significant 17% increase in peak oxygen uptake (VO2peak) and reported improvements in leisure time physical activity and quality of life, indicating that this training method can enhance physical fitness and overall well-being for individuals with SCI.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hybrid high-intensity interval training using functional electrical stimulation leg cycling and arm ski ergometer for people with spinal cord injuries: a feasibility study. Vestergaard, M., Jensen, K., Juul-Kristensen, B.[2022]

A 12-week progressive functional electric stimulation (FES) rowing training program significantly improved peak functional aerobic power in individuals with spinal cord injury, with peak oxygen consumption increasing by 11.2% and rowing distance by 25%.

The ROWSTIM II device was found to be safe and well-accepted by participants, demonstrating that FES-assisted rowing is an effective training method for enhancing aerobic capacity in this population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Functional electric stimulation-assisted rowing: Increasing cardiovascular fitness through functional electric stimulation rowing training in persons with spinal cord injury. Wheeler, GD., Andrews, B., Lederer, R., et al.[2019]

The study found that peak aerobic capacity (VO2) during both arms-only rowing and hybrid Functional Electrical Stimulation (FES)-rowing is significantly influenced by the level and duration of spinal cord injury, with a strong correlation (r = 0.67 for arms-only and r = 0.61 for FES-rowing).

FES-rowing resulted in higher peak aerobic capacities across all injury levels compared to arms-only rowing, particularly benefiting individuals with higher level injuries and those who were injured for less than 2 years, suggesting that FES-rowing may be an effective intervention for improving aerobic function post-injury.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Relationship of Spinal Cord Injury Level and Duration to Peak Aerobic Capacity With Arms-Only and Hybrid Functional Electrical Stimulation Rowing. Shaffer, RF., Picard, G., Taylor, JA.[2019]

Long-term functional electrical stimulation (FES) cycling significantly improved neurological function in individuals with chronic spinal cord injury (SCI), with an 80% responder rate compared to 40% in the control group, indicating its efficacy in promoting recovery.

Participants using FES experienced greater muscle mass and strength, with quadriceps muscle mass 36% higher and muscle strength 30-35% greater than controls, along with improved quality of life and daily functioning.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lower extremity functional electrical stimulation cycling promotes physical and functional recovery in chronic spinal cord injury. Sadowsky, CL., Hammond, ER., Strohl, AB., et al.[2021]

Functional electrical stimulation cycling exercises (FESCE) significantly reduced the rate of bone mineral density loss in the distal femur during the first 3 months after spinal cord injury in a study of 24 individuals.

However, the protective effect of FESCE did not persist after the intervention was stopped, indicating that while FESCE can help in the early stages of recovery, it does not completely prevent bone density loss in the long term.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of functional electrical stimulation cycling exercise on bone mineral density loss in the early stages of spinal cord injury. Lai, CH., Chang, WH., Chan, WP., et al.[2014]

References

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

Physiologic effects of functional electrical stimulation-induced exercises in spinal cord-injured individuals. [2007]

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

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

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

Exercise responses during functional electrical stimulation cycling in individuals with spinal cord injury. [2013]

4. England pubmed.ncbi.nlm.nih.gov

The effects of functional electrical stimulation leg cycle ergometry training on arterial compliance in individuals with spinal cord injury. [2021]

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

Functional electrical stimulation cycling in patients with chronic spinal cord injury: a pilot study. [2022]

6. England pubmed.ncbi.nlm.nih.gov

Hybrid high-intensity interval training using functional electrical stimulation leg cycling and arm ski ergometer for people with spinal cord injuries: a feasibility study. [2022]

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

Functional electric stimulation-assisted rowing: Increasing cardiovascular fitness through functional electric stimulation rowing training in persons with spinal cord injury. [2019]

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

Relationship of Spinal Cord Injury Level and Duration to Peak Aerobic Capacity With Arms-Only and Hybrid Functional Electrical Stimulation Rowing. [2019]

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

Lower extremity functional electrical stimulation cycling promotes physical and functional recovery in chronic spinal cord injury. [2021]

10. Sweden pubmed.ncbi.nlm.nih.gov

Effects of functional electrical stimulation cycling exercise on bone mineral density loss in the early stages of spinal cord injury. [2014]