Effect of a Multimodality Intervention to Improve Function and Metabolism in Spinal Cord Injury
Trial Snapshot
- Phase
- Phase 2
- Status
- Completed
- Sponsor
- Brigham and Women's Hospital
- Enrollment
- 84
- Locations
- 2
- Primary Endpoint
- peak aerobic capacity achieved during arm ergometry exercise
Study Overview
Brief Summary
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.
Detailed Description
Study Description: 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.
Objectives:
Primary Objective:
• To determine whether the multimodality intervention is more efficacious in improving peak aerobic capacity, and muscle mass and strength than placebo plus functional electrical stimulation during leg cycling (FES-LC) plus arm ergometry alone.
Secondary Objectives:
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Eligibility Criteria
- Ages
- 19 Years to 70 Years (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- Yes
Inclusion Criteria
- •Men and women, 19 to 70 years
- •Confirmed cervical and thoracic, AIS A-D who are at least 6 months post-injury and who use a wheelchair as their primary mobility mode
- •Medically stable, able to follow directions
- •Able to provide informed consent.
- •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.
Exclusion Criteria
- •Upper extremity musculoskeletal conditions (such as advanced rotator cuff pathology or carpal tunnel syndrome) or neurological disorder that in the assessment of the study investigator would prevent the participant from performing the prescribed arm ergometry.
- •Current fractures in the upper and lower extremity
- •In accordance with the Endocrine Society and ISSAM Guidelines25,52, we will exclude individuals with a contraindication for androgen use:
- •History of prostate or breast cancer
- •Prostate nodule or induration on digital rectal examination (DRE)
- •Prostate specific antigen (PSA) > 4 ng/ml or > 3 ng/ml in individuals at high risk of prostate cancer such as African Americans or those with family history of prostate cancer in first degree relatives, unless there has been a negative prostate biopsy within 3 months
- •Hematocrit > 48%
- •Conditions that would render exercise and FES unsafe or unfeasible such as severe autonomic dysreflexia, severe pressure sores, severe spasticity and severe pain.
- •Body mass index (BMI) > 45 kg/m2
- •Renal dysfunction as indicated by GFR of <50 ml/min, estimated by using the Modification of Diet in Kidney Disease (MDRD) Study equation, in accordance with K/DOQI guidelines
- •Use of testosterone or other anabolic therapies, including DHEA and androstenedione, or rhGH in the preceding 6 months
- •Active cancer requiring therapy and which may limit life expectancy to less than 5 years
- •Psychosis, bipolar disorder, or major untreated depression
- •Dementia (Mini-Mental Status Exam [MMSE] <24)
- •Myocardial infarction (MI) or stroke within 3 months of entry
- •ALT and AST > 3 x upper limit of normal
- •Poorly controlled diabetes as indicated by hemoglobin (Hb)-A1c greater than 9.0% or diabetes requiring insulin therapy
- •Blood thinners such as Coumadin, heparin, rivaroxaban (Xarelto), dabigatran (Pradaxa), lovenox (subcutaneous heparin), apixaban (Eliquis) (aspirin, plavix and other anti-platelet agents are allowed)
- •Systolic blood pressure (BP) > 170 or diastolic BP > 100 mm Hg
- •Current grade 2 or greater pressure ulcers at relevant contact sites
- •Pressure sores or open wounds on the areas that restricts their participation
- •Because the safety of testosterone has not been established in pregnancy and lactation, we will exclude pregnant or lactating women and women of childbearing potential who are sexually active but are unwilling or unable to use a reliable form of contraception. We will perform a blood test to exclude pregnancy at the time of enrollment.
- •Participation in a structured exercise program currently or in the past 2 months and unwilling to stop the structured exercise program if ongoing at time of screening. Specifically, participation in a structured exercise program, currently or in the past 2 months, that involves progressive resistance exercise training of moderate to high intensity or regular endurance exercise of moderate to high intensity, and unwillingness to stop the structured exercise program if ongoing at time of screening.
- •Inability or unwillingness to participate in the exercise training or the assessments of muscle performance and physical performance
Arms & Interventions
Multi-modality intervention group
Hybrid exercise (functional electrical stimulation - leg cycling, FES LC plus arm ergometry) plus Testosterone undecanoate
Intervention: hybrid exercise (Behavioral)
Placebo group
Hybrid exercise plus placebo medication
Intervention: hybrid exercise (Behavioral)
Multi-modality intervention group
Hybrid exercise (functional electrical stimulation - leg cycling, FES LC plus arm ergometry) plus Testosterone undecanoate
Intervention: Testosterone Undecanoate (Drug)
Outcomes
Primary Outcomes
peak aerobic capacity achieved during arm ergometry exercise
Time Frame: change from baseline to 16 weeks
The change in peak aerobic capacity from baseline to 16 weeks will be measured as the VO2 peak measured during cardiopulmonary testing using arm ergometry exercise.
Secondary Outcomes
- skeletal muscle and fat mass(16 weeks)
- whole body and regional soft tissue lean and fat mass(16 weeks)
- maximal voluntary strength in upper extremity(16 weeks)
- Muscle endurance in upper extremity(16 weeks)
- Maximal voluntary power in upper extremity(16 weeks)
- Safety Assessment(throughout 16 weeks of subjects participation)
- Self-reported function and mobility(16 weeks)
- Mood(16 weeks)
- Anxiety(16 weeks)
- Satisfaction with Life(16 weeks)
- Loneliness(16 weeks)
- Pain(16 weeks)
- Peak aerobic capacity during FES-LC exercise alone(change from baseline to 16 weeks)
- Peak aerobic capacity achieved during combined FES-LC and AE exercise(change from baseline to 16 weeks)
- metabolism measures - fasting glucose A1C(16 weeks)
- metabolism measures - lipoprotein particles(16 weeks)
- metabolism measures - insulin sensitivity(16 weeks)
- Chronotropic Index(16 weeks)
Investigators
Shalendar Bhasin, MD
Professor
Brigham and Women's Hospital