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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a combination of exercise and testosterone to improve health and wellbeing in individuals with spinal cord injuries. It focuses on those with a cervical or thoracic spinal cord injury for at least six months who primarily use a wheelchair. Researchers aim to determine if this combination can enhance aerobic capacity, function, metabolism, bone health, and overall wellbeing more effectively than exercise with a placebo. Participants should not have musculoskeletal conditions or recent serious health events, such as a heart attack. As a Phase 2 trial, the research measures the treatment's effectiveness in an initial, smaller group, allowing participants to contribute to important early-stage findings.

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.

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

Research has shown that combining leg exercises using electrical stimulation with arm workouts is generally safe for people with spinal cord injuries. Most participants handle it well, with high attendance and few dropouts.

When used correctly, testosterone undecanoate is also considered safe. It helps improve muscle and bone health in men with spinal cord injuries and usually doesn't cause major side effects. However, some concern exists about possible heart risks, so regular monitoring is important.

Previous studies have found both treatments to be well-tolerated, making them promising options for those considering joining this trial. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the hybrid exercise approach for spinal cord injury because it combines functional electrical stimulation (FES) with leg cycling and arm ergometry, which is not typical in standard care options. Unlike traditional therapies that may focus on passive or isolated muscle training, this multi-modality intervention aims to actively engage both the upper and lower body, potentially leading to more comprehensive rehabilitation outcomes. Additionally, the use of testosterone undecanoate in one of the treatment arms could enhance muscle strength and recovery, offering a novel combination not currently seen in typical rehabilitation programs. This dual approach could open new doors for improved physical function and quality of life for individuals with spinal cord injuries.

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

Research has shown that hybrid exercise, which combines leg cycling with electrical stimulation and arm exercise, can greatly improve fitness in people with spinal cord injuries (SCI). One study found this exercise more effective than others, with a moderate positive impact on heart and lung health. Electrical stimulation activates more muscles, which is crucial for boosting fitness levels despite the injury.

In this trial, participants in the multi-modality intervention group will receive both hybrid exercise and Testosterone undecanoate. Testosterone undecanoate has been shown to increase muscle mass, improve bone health, and boost metabolism in people with SCI. Studies have found that testosterone therapy can enhance muscle strength and energy, improve insulin use, and reduce belly fat. Together, these treatments show promise for improving overall health and function in individuals with SCI. ^{1 3 4 6 7}

Who Is on the Research Team?

Shalender Bhasin, MD

Principal Investigator

Brigham and Women's Hospital

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

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]

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]

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]

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]

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]

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]

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]

Citations

1. pilotfeasibilitystudies.biomedcentral.com pilotfeasibilitystudies.biomedcentral.com/articles/10.1186/s40814-022-00997-2

Hybrid high-intensity interval training using functional ... The aim was to assess safety and feasibility of Hybrid High-Intensity Interval Training (HIIT) using Functional Electrical Stimulation (FES) leg cycling and ...

2. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0003999323002253

Effects of Functional Electrical Stimulation Cycling ... During acute bouts of exercise, hybrid FES cycling was moderately more effective than ACE (effect size [ES] of 0.59 (95% CI 0.15-1.02, P=.008) in increasing V̇o ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4252514/

Hybrid Functional Electrical Stimulation Exercise Training ... That is, FES_RT effectively circumvents the effect of the spinal cord injury on peak aerobic capacity by engaging more muscle mass, independent ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5791928/

Arm Cycling Combined with Passive Leg Cycling Enhances ... PLC during ACE for SCI-high adults appears to facilitate exercise at a higher VO 2 and so may be sufficient to promote cardiovascular fitness.

5. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0003999397900782

Physiologic responses during functional electrical ... Objectives: (1) To determine if a hybrid exercise (leg plus arm) training program performed immediately after functional electrical stimulation (FES) leg ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/35193705/

Hybrid high-intensity interval training using functional ... Hybrid HIIT was safe for people with SCI paraplegia. The majority of the criteria for feasibility were met with acceptable attendance rate, limited drop out.

7. cyclonemobility.com cyclonemobility.com/wp-content/uploads/2018/08/SCI-FES-Evidence.pdf

FES Cycle Ergometry for Spinal Cord Injury Muscle atrophy is prevented in patients with acute spinal cord injury using functional electrical stimulation.