Locomotor Training + Testosterone for Spinal Cord Injury
Recruiting in Palo Alto (17 mi)
+1 other location
Age: 18+
Sex: Male
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 2
Recruiting
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
Prior Safety Data
Trial Summary
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.
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.
12345Is 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.
12367How 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.
12467Eligibility Criteria
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
Men who are older than 18 years.
Your testosterone levels are too low.
+6 more
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
+30 more
Trial Timeline
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
Participant Groups
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.
3Treatment groups
Experimental Treatment
Active Control
Group I: testosterone enanthateExperimental Treatment1 Intervention
Testosterone enanthate via i.m. injection (100 mg/week)
Group II: locomotor training, testosterone enanthateExperimental Treatment2 Interventions
Treadmill and overground walking training and testosterone enanthate via i.m. injection (100 mg/week)
Group III: non-interventional controlActive Control1 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
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Brooks RehabilitationJacksonville, FL
North Florida/South Georgia Veterans Health SystemGainesville, FL
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Who Is Running the Clinical Trial?
North Florida Foundation for Research and EducationLead Sponsor
North Florida/South Georgia Veterans Health SystemCollaborator
Brooks RehabilitationCollaborator
University of FloridaCollaborator
References
Testosterone replacement therapy and motor function in men with spinal cord injury: a retrospective analysis. [2016]To evaluate motor function in men with spinal cord injury (SCI) given testosterone replacement therapy (TRT).
Activity-Based Physical Rehabilitation with Adjuvant Testosterone to Promote Neuromuscular Recovery after Spinal Cord Injury. [2018]Neuromuscular impairment and reduced musculoskeletal integrity are hallmarks of spinal cord injury (SCI) that hinder locomotor recovery. These impairments are precipitated by the neurological insult and resulting disuse, which has stimulated interest in activity-based physical rehabilitation therapies (ABTs) that promote neuromuscular plasticity after SCI. However, ABT efficacy declines as SCI severity increases. Additionally, many men with SCI exhibit low testosterone, which may exacerbate neuromusculoskeletal impairment. Incorporating testosterone adjuvant to ABTs may improve musculoskeletal recovery and neuroplasticity because androgens attenuate muscle loss and the slow-to-fast muscle fiber-type transition after SCI, in a manner independent from mechanical strain, and promote motoneuron survival. These neuromusculoskeletal benefits are promising, although testosterone alone produces only limited functional improvement in rodent SCI models. In this review, we discuss the (1) molecular deficits underlying muscle loss after SCI; (2) independent influences of testosterone and locomotor training on neuromuscular function and musculoskeletal integrity post-SCI; (3) hormonal and molecular mechanisms underlying the therapeutic efficacy of these strategies; and (4) evidence supporting a multimodal strategy involving ABT with adjuvant testosterone, as a potential means to promote more comprehensive neuromusculoskeletal recovery than either strategy alone.
Bone and non-contractile soft tissue changes following open kinetic chain resistance training and testosterone treatment in spinal cord injury: an exploratory study. [2021]Twenty men with spinal cord injury (SCI) were randomized into two 16-week intervention groups receiving testosterone treatment (TT) or TT combined with resistance training (TT + RT). TT + RT appears to hold the potential to reverse or slow down bone loss following SCI if provided over a longer period.
Acute effects of locomotor training on neuromuscular and metabolic profile after incomplete spinal cord injury. [2022]Locomotor training (LT) enhances walking in individuals with spinal cord injuries (SCIs). We tested the acute effects of 4 days of LT using BWSTT combined with Robotic Locomotor therapy compared to BWSTT twice weekly.
Prevalence of testosterone deficiency after spinal cord injury. [2015]To define the prevalence of testosterone deficiency in persons with chronic spinal cord injury (SCI) and to identify factors associated with this deficiency.
Locomotor training with adjuvant testosterone preserves cancellous bone and promotes muscle plasticity in male rats after severe spinal cord injury. [2021]Loading and testosterone may influence musculoskeletal recovery after spinal cord injury (SCI). Our objectives were to determine (a) the acute effects of bodyweight-supported treadmill training (TM) on hindlimb cancellous bone microstructure and muscle mass in adult rats after severe contusion SCI and (b) whether longer-term TM with adjuvant testosterone enanthate (TE) delivers musculoskeletal benefit. In Study 1, TM (40 min/day, 5 days/week, beginning 1 week postsurgery) did not prevent SCI-induced hindlimb cancellous bone loss after 3 weeks. In Study 2, TM did not attenuate SCI-induced plantar flexor muscles atrophy nor improve locomotor recovery after 4 weeks. In our main study, SCI produced extensive distal femur and proximal tibia cancellous bone deficits, a deleterious slow-to-fast fiber-type transition in soleus, lower muscle fiber cross-sectional area (fCSA), impaired muscle force production, and levator ani/bulbocavernosus (LABC) muscle atrophy after 8 weeks. TE alone (7.0 mg/week) suppressed bone resorption, attenuated cancellous bone loss, constrained the soleus fiber-type transition, and prevented LABC atrophy. In comparison, TE+TM concomitantly suppressed bone resorption and stimulated bone formation after SCI, produced near-complete cancellous bone preservation, prevented the soleus fiber-type transition, attenuated soleus fCSA atrophy, maintained soleus force production, and increased LABC mass. 75% of SCI+TE+TM animals recovered voluntary over-ground hindlimb stepping, while no SCI and only 20% of SCI+TE animals regained stepping ability. Positive associations between testosterone and locomotor function suggest that TE influenced locomotor recovery. In conclusion, short-term TM alone did not improve bone, muscle, or locomotor recovery in adult rats after severe SCI, while longer-term TE+TM provided more comprehensive musculoskeletal benefit than TE alone.
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]The dose de-escalation (DD) effects of testosterone and evoked resistance training (RT) on body composition, cardiometabolic, and neuromuscular variables were investigated. Thirteen men with chronic complete spinal cord injury (SCI) were followed for additional 16 weeks after receiving either testosterone treatment only (TT) or TT+RT. During the 16-week DD period, the TT+RT group underwent a program of once weekly electrical stimulation with gradually decreasing ankle weights and testosterone patches of 2 mg day-1 (TT+RT group). The TT only group did not receive any intervention throughout the detraining period (no-TT group). Body composition was tested using anthropometrics, dual energy X-ray absorptiometry, and magnetic resonance imaging. After an overnight fast, basal metabolic rate (BMR), lipid panel, serum testosterone, inflammatory biomarkers, glucose effectiveness, and insulin sensitivity were measured. Finally, peak isometric and isokinetic torques were measured only in the TT+RT group. All measurements were conducted at the beginning and at the end of DD. Absolute thigh muscle cross-sectional areas (CSAs) demonstrated interaction effects (p < 0.05) between the TT+RT (-8.15%, -6.5%) and no-TT (2.3%, 4.4%) groups. Similarly, absolute knee extensor muscle CSA demonstrated interaction effects (p < 0.05) between the TT+RT (-11%, -7.0%) and no-TT (2.6%, 3.8%) groups. There was a trend (p = 0.07) of increasing visceral adipose tissue (VAT) CSAs in the TT+RT (18%) and in the no-TT (16% cm2 ) groups. There was an interaction (p = 0.005) between TT+RT (decreased by 3.7%) and no-TT groups (increased by 9.0%) in BMR. No interactions were evident between groups over time for biomarkers related to carbohydrate, lipid metabolism, or inflammation. Finally, there were no changes (p > 0.05) in peak isometric or isokinetic torques and rise time following 16 weeks of the DD period in the TT+RT group. TT+RT during 16 weeks of DD was minimally effective at preventing detraining relative to no-TT on muscle size, BMR, and VAT. However, neuromuscular gains were successfully maintained.