Multimodality Intervention for Function and Metabolism in SCI

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 88 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)

Details