Testosterone and long pulse width stimulation (TLPS) for denervated muscles after spinal cord injury: a study protocol of randomised clinical trial.

INTRODUCTION: Long pulse width stimulation (LPWS; 120-150 ms) has the potential to stimulate denervated muscles and to restore muscle size in denervated people with spinal cord injury (SCI). We will determine if testosterone treatment (TT)+LPWS would increase skeletal muscle size, leg lean mass and improve overall metabolic health in persons with SCI with denervation. We hypothesise that the 1-year TT+LPWS will upregulate protein synthesis pathways, downregulate protein degradation pathways and increase overall mitochondrial health. METHODS AND ANALYSIS: Twenty-four male participants (aged 18-70 years with chronic SCI) with denervation of both knee extensor muscles and tolerance to the LPWS paradigm will be randomised into either TT+neuromuscular electrical stimulation via telehealth or TT+LPWS. The training sessions will be twice weekly for 1 year. Measurements will be conducted 1 week prior training (baseline; week 0), 6 months following training (postintervention 1) and 1 week after the end of 1 year of training (postintervention 2). Measurements will include body composition assessment using anthropometry, dual X-ray absorptiometry and MRI to measure size of different muscle groups. Metabolic profile will include measuring of basal metabolic rate, followed by blood drawn to measure fasting biomarkers similar to hemoglobin A1c, lipid panels, C reactive protein, interleukin-6 and free fatty acids and then intravenous glucose tolerance test to test for insulin sensitivity and glucose effectiveness. Finally, muscle biopsy will be captured to measure protein expression and intracellular signalling; and mitochondrial electron transport chain function. The participants will fill out 3 days dietary record to monitor their energy intake on a weekly basis. ETHICS AND DISSEMINATION: The study was approved by Institutional Review Board of the McGuire Research Institute (ID # 02189). Dissemination plans will include the Veteran Health Administration and its practitioners, the national SCI/D services office, the general healthcare community and the veteran population, as well as the entire SCI community via submitting quarterly letters or peer-review articles. TRIAL REGISTRATION NUMBER: NCT03345576.

Skeletal muscle hypertrophy and attenuation of cardio-metabolic risk factors (SHARC) using functional electrical stimulation-lower extremity cycling in persons with spinal cord injury: study protocol for a randomized clinical trial.

BACKGROUND: Persons with spinal cord injury (SCI) are at heightened risks of developing unfavorable cardiometabolic consequences due to physical inactivity. Functional electrical stimulation (FES) and surface neuromuscular electrical stimulation (NMES)-resistance training (RT) have emerged as effective rehabilitation methods that can exercise muscles below the level of injury and attenuate cardio-metabolic risk factors. Our aims are to determine the impact of 12 weeks of NMES + 12 weeks of FES-lower extremity cycling (LEC) compared to 12 weeks of passive movement + 12 weeks of FES-LEC on: (1) oxygen uptake (VO2), insulin sensitivity, and glucose disposal in adults with SCI; (2) skeletal muscle size, intramuscular fat (IMF), and visceral adipose tissue (VAT); and (3) protein expression of energy metabolism, protein molecules involved in insulin signaling, muscle hypertrophy, and oxygen uptake and electron transport chain (ETC) activities. METHODS/DESIGN: Forty-eight persons aged 18-65 years with chronic (> 1 year) SCI/D (AIS A-C) at the C5-L2 levels, equally sub-grouped by cervical or sub-cervical injury levels and time since injury, will be randomized into either the NMES + FES group or Passive + FES (control group). The NMES + FES group will undergo 12 weeks of evoked RT using twice-weekly NMES and ankle weights followed by twice-weekly progressive FES-LEC for an additional 12 weeks. The control group will undergo 12 weeks of passive movement followed by 12 weeks of progressive FES-LEC. Measurements will be performed at baseline (B; week 0), post-intervention 1 (P1; week 13), and post-intervention 2 (P2; week 25), and will include: VO2 measurements, insulin sensitivity, and glucose effectiveness using intravenous glucose tolerance test; magnetic resonance imaging to measure muscle, IMF, and VAT areas; muscle biopsy to measure protein expression and intracellular signaling; and mitochondrial ETC function. DISCUSSION: Training through NMES + RT may evoke muscle hypertrophy and positively impact oxygen uptake, insulin sensitivity, and glucose effectiveness. This may result in beneficial outcomes on metabolic activity, body composition profile, mitochondrial ETC, and intracellular signaling related to insulin action and muscle hypertrophy. In the future, NMES-RT may be added to FES-LEC to improve the workloads achieved in the rehabilitation of persons with SCI and further decrease muscle wasting and cardio-metabolic risks. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02660073 . Registered on 21 Jan 2016.

Mental disorder prevalence among U.S. Department of Veterans Affairs outpatients with spinal cord injuries.

OBJECTIVES: Depression and other mental disorders are more prevalent among individuals living with spinal cord injury (SCI) than in the community at large, and have a strong association with quality of life. Yet little is known about the prevalence and predictors of mental disorders among U.S. military Veterans living with SCI. The primary aim of this study was to present an estimate of mental disorder point prevalence in this population. The secondary aim was to examine the relationship of mental disorders to demographics, injury characteristics, and other clinically relevant features such as impairment from mental health problems and life satisfaction. DESIGN: Cross-sectional. SETTING: A SCI & Disorders Center at a U.S. Veterans Affairs Medical Center. PARTICIPANTS/METHODS: Administrative and medical records of 280 Veterans who attended annual comprehensive SCI evaluations were evaluated. Demographics, injury characteristics, self-reported mental and emotional functioning (i.e. SF-8 Health Survey), and clinician-determined mental disorder diagnoses were attained. RESULTS: Overall, 40% of patients received at least one mental disorder diagnosis, most commonly depressive disorders (19%), posttraumatic stress disorder (12%), and substance or alcohol use disorders (11%). Several patient characteristics predicted mental disorders, including age, racial minority identity, non-traumatic SCI etiology, and incomplete (i.e. AIS D) vs. complete injury. Mental disorders were associated with greater impairment from health and mental health-related problems and less satisfaction with life. CONCLUSIONS: Mental disorders are common among outpatients receiving VA specialty care for SCI. These findings highlight the importance of having adequate and effective available mental health services available for Veterans with SCI.

Body composition changes with testosterone replacement therapy following spinal cord injury and aging: A mini review.

Context Hypogonadism is a male clinical condition in which the body does not produce enough testosterone. Testosterone plays a key role in maintaining body composition, bone mineral density, sexual function, mood, erythropoiesis, cognition and quality of life. Hypogonadism can occur due to several underlying pathologies during aging and in men with physical disabilities, such as spinal cord injury (SCI). This condition is often under diagnosed and as a result, symptoms undertreated. Methods In this mini-review, we propose that testosterone replacement therapy (TRT) may be a viable strategy to improve lean body mass (LBM) and fat mass (FM) in men with SCI. Evidence Synthesis Supplementing the limited data from SCI cohorts with consistent findings from studies in non-disabled aging men, we present evidence that, relative to placebo, transdermal TRT can increase LBM and reduce FM over 3-36 months. The impact of TRT on bone mineral density and metabolism is also discussed, with particular relevance for persons with SCI. Moreover, the risks of TRT remain controversial and pertinent safety considerations related to transdermal administration are outlined. Conclusion Further research is necessary to help develop clinical guidelines for the specific dose and duration of TRT in persons with SCI. Therefore, we call for more high-quality randomized controlled trials to examine the efficacy and safety of TRT in this population, which experiences an increased risk of cardiometabolic diseases as a result of deleterious body composition changes after injury.

A feasibility pilot using telehealth videoconference monitoring of home-based NMES resistance training in persons with spinal cord injury.

INTRODUCTION: The objective of the study was to investigate the feasibility and initial efficacy of telehealth communication in conjunction with surface neuromuscular electrical stimulation (NMES) resistance training (RT) to induce muscle hypertrophy. MATERIALS AND METHODS: This was a home-based setting of within-subject control design of trained vs controlled limbs. Five men with chronic (>1 year postinjury) motor-complete spinal cord injury (SCI) participated in a twice-weekly telehealth videoconference program using home-based NMES-RT for 8 weeks. Stimulation was applied to the knee extensor muscle group of the trained leg, while the untrained leg served as a control. Participants received real-time feedback to ensure a proper setup of electrodes and stimulator to monitor subject safety throughout the entire training session. Magnetic resonance imaging was used to measure cross-sectional areas (CSAs) and intramuscular fat (IMF) of the whole thigh and individual muscle groups. Average two-way travel time, distance traveled in miles and total cost of gas per mile were calculated. RESULTS: Participants had 100% compliance. Trained whole and absolute knee extensor muscle CSA increased by 13% (P=0.002) and 18% (P=0.0002), with no changes in the controlled limb. Absolute knee flexor and adductor CSAs increased by 3% (P=0.02) and 13% (P=0.0001), respectively. Absolute whole thigh and knee extensor IMF CSAs decreased significantly in the trained limb by 14% (P=0.01) and 36% (P=0.0005), respectively, with no changes in controlled limb. DISCUSSION: The pilot work documented that using telehealth communication is a safe, feasible and potentially cost-reducing approach for monitoring home-based NMES-RT in persons with chronic SCI. All trained muscles showed detectable muscle hypertrophy with concomitant decrease in ectopic adipose tissue.

Effects of Testosterone and Evoked Resistance Exercise after Spinal Cord Injury (TEREX-SCI): study protocol for a randomised controlled trial.

INTRODUCTION: Individuals with spinal cord injury (SCI) are at a lifelong risk of obesity and chronic metabolic disorders including insulin resistance and dyslipidemia. Within a few weeks of injury, there is a significant decline in whole body fat-free mass, particularly lower extremity skeletal muscle mass, and subsequent increase in fat mass (FM). This is accompanied by a decrease in anabolic hormones including testosterone. Testosterone replacement therapy (TRT) has been shown to increase skeletal muscle mass and improve metabolic profile. Additionally, resistance training (RT) has been shown to increase lean mass and reduce metabolic disturbances in SCI and other clinical populations. METHODS AND ANALYSIS: 26 individuals with chronic, motor complete SCI between 18 and 50 years old were randomly assigned to a RT+TRT group (n=13) or a TRT group (n=13). 22 participants completed the initial 16-week training phase of the study and 4 participants withdrew. 12 participants of the 22 completed 16 weeks of detraining. The TRT was provided via transdermal testosterone patches (4-6 mg/day). The RT+TRT group had 16 weeks of supervised unilateral progressive RT using surface neuromuscular electrical stimulation with ankle weights. This study will investigate the effects of evoked RT+TRT or TRT alone on body composition (muscle cross-sectional area, visceral adipose tissue, %FM) and metabolic profile (glucose and lipid metabolism) in individuals with motor complete SCI. Findings from this study may help in designing exercise therapies to alleviate the deterioration in body composition after SCI and decrease the incidence of metabolic disorders in this clinical population. ETHICS AND DISSEMINATION: The study is currently approved by the McGuire VA Medical Center and Virginia Commonwealth University. All participants read and signed approved consent forms. Results will be submitted to peer-reviewed journals and presented at national and international conferences. TRIAL REGISTRATION NUMBER: Pre-result, NCT01652040.

Frequency of Dietary Recalls, Nutritional Assessment, and Body Composition Assessment in Men With Chronic Spinal Cord Injury.

OBJECTIVES: To assess different frequencies of dietary recalls while evaluating caloric intake and the percentage of macronutrients in men with spinal cord injury (SCI) and to examine the relations between caloric intake or percentage of macronutrients and assessment of whole and regional body composition using dual-energy x-ray absorptiometry. DESIGN: Cross-sectional and longitudinal. SETTING: Laboratory and hospital. PARTICIPANTS: Men with chronic (>1 y postinjury) motor complete SCI (N=16). INTERVENTIONS: Participants were asked to turn in a 5-day dietary recall on a weekly basis for 4 weeks. The averages of 5-, 3-, and 1-day dietary recalls for caloric intake and percentage of macronutrients (carbohydrates, fat, protein) were calculated. Body composition was evaluated using whole-body dual-energy x-ray absorptiometry. After overnight fast, basal metabolic rate (BMR) was evaluated using indirect calorimetry and total energy expenditure (TEE) was estimated. MAIN OUTCOME MEASURES: Caloric intake, percentage of macronutrients, BMR, and body composition. RESULTS: Caloric intake and percentage of macronutrients were not different after using 5-, 3-, and 1-day dietary recalls (P>.05). Caloric intake was significantly lower than TEE (P<.05). The percentage of fat accounted for 29% to 34% of the whole and regional body fat mass (P=.037 and P=.022). The percentage of carbohydrates was positively related to the percentage of whole-body lean mass (r=.54; P=.037) and negatively related to the percentage of fat mass. CONCLUSIONS: The frequency of dietary recalls does not vary while evaluating caloric intake and macronutrients. Total caloric intake was significantly lower than the measured BMR and TEE. Percentages of dietary fat and carbohydrates are related to changes in body composition after SCI.

Effect of adjusting pulse durations of functional electrical stimulation cycling on energy expenditure and fatigue after spinal cord injury.

The purpose of the current study was to determine the effects of three different pulse durations (200, 350, and 500 microseconds [P200, P350, and P500, respectively]) on oxygen uptake (VO2), cycling performance, and energy expenditure (EE) percentage of fatigue of the knee extensor muscle group immediately and 48 to 72 h after cycling in persons with spinal cord injury (SCI). A convenience sample of 10 individuals with motor complete SCI participated in a repeated-measures design using a functional electrical stimulation (FES) cycle ergometer over a 3 wk period. There was no difference among the three FES protocols on relative VO2 or cycling EE. Delta EE between exercise and rest was 42% greater in both P500 and P350 compared with P200 (p = 0.07), whereas recovery VO2 was 23% greater in P350 compared with P200 (p = 0.03). There was no difference in the outcomes of the three pulse durations on muscle fatigue. Knee extensor torque significantly decreased immediately after (p < 0.001) and 48 to 72 h after (p < 0.001) FES leg cycling. Lengthening pulse duration did not affect submaximal or relative VO2 or EE, total EE, and time to fatigue. Greater recovery VO2 and delta EE were noted in P350 and P500 compared with P200. An acute bout of FES leg cycling resulted in torque reduction that did not fully recover 48 to 72 h after cycling.

Locomotor and resistance training restore walking in an elderly person with a chronic incomplete spinal cord injury.

OBJECTIVE: To determine the effects of 10~weeks of locomotor training (LT) using body weight supported (BWS) treadmill training and resistance training (RT) programs on over-ground walking recovery, walking speed and distance, functional independent measure (FIM), walking index for spinal cord injury (WISCI) and Berg Balance Score in an elderly person with an incomplete spinal cord injury (SCI). DESIGN: A 66 year-old-male with a chronic incomplete SCI at C5/C6 ASIA Impairment Scale (AIS) D was admitted for rehabilitation following posterior laminectomy at L3-L5. The participant was a short distance ambulator relying primarily on his power wheelchair for mobility. He completed 10~weeks of LT using manual BWS treadmill twice weekly and RT for knee extensor muscle groups twice a week. A weekly test of the over-ground distance and speed were recoded over the course of the 10~weeks. Additionally, the participant underwent a three month evaluation after discharge. RESULTS: The 10-week program resulted in independent use of bilateral Canadian crutches to ambulate for 200 feet and increased over-ground walking speed. The FIM score increased from 3 to 6 and Berg balance score increased from 11 to 41. The WISCI score increased from 1 to 10. Three months post-discharge, the participant maintained his functional independency in sit to stand activity and over-ground walking. CONCLUSION: A combined program of LT and RT could enhance walking recovery in a person with a long-term SCI. The findings suggest that twice a week of LT can promote motor recovery if it is accompanied with an approach that effectively loads the paralyzed lower extremities.