Multimodality Intervention for Function and Metabolism in SCI
- Conditions
- Spinal Cord Injuries
- Interventions
- Behavioral: hybrid exercise
- Registration Number
- NCT03576001
- Lead Sponsor
- Brigham and Women's Hospital
- 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:
* To determine whether the multimodality intervention is more efficacious than placebo plus functional electrical stimulation during leg cycling (FES-LC) plus arm ergometry in improving metabolic health, as reflected in fasting glucose, hemoglobin A1C, insulin sensitivity, fat mass and distribution, plasma lipids, and inflammation markers.
* To determine whether the multimodality intervention is more efficacious than placebo plus functional electrical stimulation during leg cycling (FES-LC) plus arm ergometry in improving volumetric and areal bone density, bone microarchitecture, and bone strength.
To determine the efficacy of the multimodality intervention in improving self-reported physical function (using SCI-FI AT and wellbeing (mood, anxiety, pain, loneliness and life satisfaction)
• To assess safety by structured monitoring of adverse events, and determining the proportion of participants experiencing injury, erythrocytosis, or other androgen-related or exercise-related adverse events.
Endpoints: Primary Endpoint:
Our primary outcome is peak aerobic capacity because it is an excellent marker of overall health, physical function, and mortality. Aerobic capacity is closely related to metabolic health, insulin sensitivity and cardiovascular outcomes. It can be measured accurately in SCI patients and would be expected to improve with the proposed interventions.
Secondary endpoints. Whole body skeletal muscle and fat mass and intraabdominal fat will be assessed by magnetic resonance imaging (MRI), using the Dixon method for separation of water/ fat signals. Body composition will also be measured by DEXA.
Maximal voluntary strength and muscle fatigability in the upper extremity will be assessed using the 1-repetition maximum in chest press.
Total, trabecular and cortical volumetric bone density; trabecular and cortical microarchitecture, both measured using high resolution peripheral quantitative computed tomography (HR-pQCT) at the ultradistal tibia, proximal tibia, and ultradistal radius.
Estimated bone strength of the ultradistal tibia and radius, assessed using microfinite element analysis of the HR-pQCT data.
Areal bone mineral density of the hip and lumbar spine using dual-energy X-ray absorptiometry (DEXA). (aBMD will be measured because DEXA is a clinically used and accepted measure of bone density, and aBMD is predictive of fracture risk.) Serum bone turnover markers, including markers of bone formation (osteocalcin, bone specific alkaline phosphatase (BSAP), (PINP) and bone resorption (CTX).
Spinal Cord Injury - Functional Index (SCI-FI) will be used to assess self-reported function and mobility. SCI-FI is specific for persons with SCI that assesses functional capacity in basic mobility, ambulation, self-care, and fine motor function, and wheelchair ambulation.
Measures of Metabolism: Fasting glucose, A1C; insulin sensitivity using HOMA-IR; IL-6 and hsCRP as inflammation markers; and plasma lipids, apolipoproteins B, C and A, and lipoprotein particles as markers of atherogenicity - all measured in the Brigham Research Assay Laboratory. Visceral fat will be assessed using Dixon MRI technique.
Wellbeing: We will assess mood, anxiety, pain, and life satisfaction as measures of wellbeing. Mood will be assessed using Patient Health Questionnaire (PHQ-9), a 9-item scale that assesses mood and depressive symptoms. We will assess anxiety using GAD-7. Modified Brief Pain Inventory (BPI), a validated measure of pain in SCI, assesses pain intensity (sensory dimension) and interference with function (reactive dimension). Satisfaction with Life Scale is a 5-item scale that assesses happiness with life. Loneliness will be assessed using the Three-Item Loneliness Scale.
Study Population: This proof-of-concept trial will enroll 88 community dwelling men and women with SCI, 19 to 70 years of age, motor C7-T12 cervical and thoracic, AIS A, B, C, or D, 6 months or later after a SCI.
The trial plans to randomize 84 eligible subjects at a single trial site.
Phase: Phase 2
Description of Sites/Facilities Enrolling Participants: This is a single site study that will take place at the Brigham and Women's Hospital in Boston, MA.
Description of Study Intervention: The Home-Based Multimodality Functional Recovery and Metabolic Health Enhancement Program includes training at home consisting of FES-LC plus arm ergometry plus testosterone undecanoate. Testosterone injections will be administered by study staff in the research clinic or by a visiting nurse in the participant's home. The control group will receive FES-LC plus arm ergometry plus placebo injections.
Study Duration: Approximately 54 months
Participant Duration: Approximately 33 weeks (14 weeks for screening, baseline studies, and Day 1, 16 weeks of intervention, and up to 3 weeks of end of study assessments)
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 84
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Multi-modality intervention group Testosterone Undecanoate Hybrid exercise (functional electrical stimulation - leg cycling, FES LC plus arm ergometry) plus Testosterone undecanoate Multi-modality intervention group hybrid exercise Hybrid exercise (functional electrical stimulation - leg cycling, FES LC plus arm ergometry) plus Testosterone undecanoate Placebo group hybrid exercise Hybrid exercise plus placebo medication
- Primary Outcome Measures
Name Time Method peak aerobic capacity achieved during arm ergometry exercise 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 Outcome Measures
Name Time Method Safety Assessment throughout 16 weeks of subjects participation Adverse and Serious Adverse Event recording classified using MEDRA and SOC coding
Self-reported function and mobility 16 weeks self-reported function and mobility measured by the Spinal Cord Injury Function Index (SCI-FI). The score range is 13 to 52, with higher scores indicating better function and mobility.
skeletal muscle and fat mass 16 weeks magnetic resonance imaging (MRI) using the Dixon method
whole body and regional soft tissue lean and fat mass 16 weeks Measured using DXA
maximal voluntary strength in upper extremity 16 weeks 1-repetition maximum strength in the seated chest press exercise, measured in force units (Newtons)
Muscle endurance in upper extremity 16 weeks muscle endurance in the seated chest press exercise, measured in number of repetitions to failure
Maximal voluntary power in upper extremity 16 weeks muscle power in the seated chest press exercise, measured in Watts.
Mood 16 weeks Patient Health Questionnaire (PHQ-9). The score range is 0 to 27. A higher score indicates more severe depression.
Anxiety 16 weeks Generalized Anxiety Disorder 7-item scale (GAD-7). Score range is 0 to 21. A higher score indicates worse anxiety.
Satisfaction with Life 16 weeks Satisfaction with Life Scale (5 item scale). The score range is from 5 to 35. Higher scores indicate more satisfaction with life.
Loneliness 16 weeks Three-Item Loneliness Scale. Score range is 2 to 8, with a score of 2 indicating the least loneliness and 8 the most loneliness
Pain 16 weeks Brief Pain Inventory (BPI). Score range is 0 to 10. Higher scores indicate worse pain.
Peak aerobic capacity during FES-LC exercise alone change from baseline to 16 weeks Change from baseline in peak V02 aerobic capacity achieved during the functional electrical stimulation -leg cycle (FES-LC) exercise alone
Peak aerobic capacity achieved during combined FES-LC and AE exercise change from baseline to 16 weeks The change from baseline in the V02 peak aerobic capacity during the combined functional electrical stimulation- leg cycling (FES-LC) and arm ergometry (AE) exercise
metabolism measures - fasting glucose A1C 16 weeks The percent fasting glucose A1C at final outcome assessment
metabolism measures - lipoprotein particles 16 weeks lipoprotein particles at final outcome assessment, measured as mg/dL
metabolism measures - insulin sensitivity 16 weeks insulin sensitivity at final outcome assessment, measured as Homeostatic Model Assessment - Insulin Resistance Index.
Chronotropic Index 16 weeks The Chronotropic Index is the slope of heart rate (HR) versus whole body oxygen uptake (VO2) measured while subjects are performing a progressive work test using cycle ergometry.
Trial Locations
- Locations (1)
Brigham and Women's Hospital
🇺🇸Boston, Massachusetts, United States