Development and deployment of an at-home strength and conditioning program to support a phase I trial in persons with chronic spinal cord injury.

STUDY DESIGN: Nonrandomized clinical trial (NCT02354625). OBJECTIVES: As a part of a Phase I clinical trial to assess the safety of autologous human Schwann cells (ahSC) in persons with chronic spinal cord injury (SCI), participants engaged in a multimodal conditioning program pre- and post-ahSC transplantation. The program included a home-based strength and endurance training program to prevent lack of fitness and posttransplantation detraining from confounding potential ahSC therapeutic effects. This paper describes development, deployment, outcomes, and challenges of the home-based training program. SETTING: University-based laboratory. METHODS: Development phase: two men with paraplegia completed an 8-week laboratory-based 'test' of the home-based program. Deployment phase: the first four (two males, two females) participant cohort of the ahSC trial completed the program at home for 12 weeks pre and 20 weeks post ahSC transplant. RESULTS: Development phase: both participants improved their peak aerobic capacity (VO2peak) (≥17%), peak power output (POpeak) (≥8%), and time to exhaustion (TTE) (≥7%). Deployment phase: pretransplant training minimally increased fitness in the two male participants (≥6% POpeak and ≥9% TTE). The two women had no POpeak changes and slight TTE changes (+2.6 and -1.2%, respectively.) All four participants detrained during the posttransplant recovery period. After posttransplant retraining, all four participants increased TTE (4-24%), three increased VO2peak (≥11%), and two increased POpeak (≥7%). CONCLUSIONS: Home-based strength and condition programs can be effective and successfully included in therapeutic SCI trials. However, development of these programs requires substantial content knowledge and experience.

Physiological responses to moderate intensity continuous and high-intensity interval exercise in persons with paraplegia.

STUDY DESIGN: Randomized crossover. OBJECTIVES: To test differences in the duration and magnitude of physiological response to isocaloric moderate intensity continuous (MICE) and high-intensity interval exercise (HIIE) sessions in persons with spinal cord injury (SCI). SETTING: Academic medical center in Miami, FL, USA. METHODS: Ten adult men (mean ± s.d.; 39 ± 10 year old) with chronic (13.2 ± 8.8 year) paraplegia (T2-T10) completed a graded exercise test. Then, in a randomized order, participants completed MICE and HIIE for a cost of 120 kcal. MICE was performed at 24.6% POpeak. During HIIE, exercise was completed in 2 min work and recovery phases at 70%:10% POpeak. RESULTS: MICE and HIIE were isocaloric (115.9 ± 21.8 and 116.6 ± 35.0 kcal, respectively; p = 0.903), but differed in duration (39.8 ± 4.6 vs 32.2 ± 6.2 min; p < 0.001) and average respiratory exchange ratio (RER; 0.90 ± 0.08 vs 1.01 ± 0.07; p = 0.002). During MICE, a workrate of 24.6 ± 6.7% POpeak elicited a V̇O2 of 53.1 ± 6.5% V̇O2peak (10.1 ± 2.2 ml kg-1 min-1). During HIIE, a workrate at 70% POpeak elicited 88.3 ± 6.7% V̇O2peak (16.9 ± 4.2 ml kg-1 min-1), and 29.4 ± 7.7% of the session was spent at or above 80% V̇O2peak. During HIIE working phase, RER declined from the first to last interval (1.08 ± 0.07 vs 0.98 ± 0.09; p < 0.001), reflecting an initially high but declining glycolytic rate. CONCLUSIONS: Compared with MICE, HIIE imposed a greater physiological stimulus while requiring less time to achieve a target caloric expenditure. Thus, exercise intensity might be an important consideration in the tailoring of exercise prescription to address the cardiometabolic comorbidities of SCI.

Differences in Acute Metabolic Responses to Bionic and Nonbionic Ambulation in Spinal Cord Injured Humans and Controls.

OBJECTIVES: To (1) compare energy expenditure during seated rest, standing, and prolonged bionic ambulation or bipedal ambulation in participants with spinal cord injury (SCI) and noninjured controls, respectively, and (2) test effects on postbionic ambulation glycemia in SCI. DESIGN: Two independent group comparison of SCI and controls. SETTING: Academic Medical Center. PARTICIPANTS: Ten participants with chronic SCI (C7-T1, American Spinal Injury Association Impairment Scale A-C) and 10 controls (N=20). INTERVENTIONS: A commercial bionic exoskeleton. MAIN OUTCOME MEASURES: Absolute and relative (to peak) oxygen consumption, perceived exertion, carbohydrate/fat oxidation, energy expenditure, and postbionic ambulation plasma glucose/insulin. RESULTS: Average work intensity accompanying 45 minutes of outdoor bionic ambulation was <40% peak oxygen consumption, with negligible drift after reaching steady state. Rating of perceived exertion (RPE) did not differ between groups and reflected low exertion. Absolute energy costs for bionic ambulation and nonbionic ambulation were not different between groups despite a 565% higher ambulation velocity in controls and 3.3× higher kilocalorie per meter in SCI. Fuel partitioning was similar between groups and the same within groups for carbohydrate and fat oxidation. Nonsignificant (9%) lowering of the area under a glucose tolerance curve following bionic ambulation required 20% less insulin than at rest. CONCLUSION: Work intensity during prolonged bionic ambulation for this bionic exoskeleton is below a threshold for cardiorespiratory conditioning but above seated rest and passive standing. Bionic ambulation metabolism is consistent with low RPE and unchanged fuel partitioning from seated rest. Bionic ambulation did not promote beneficial effects on glycemia in well-conditioned, euglycemic participants. These findings may differ in less fit individuals with SCI or those with impaired glucose tolerance. Observed trends favoring this benefit suggest they are worthy of testing.

Interrater and intrarater reliability of ventilatory thresholds determined in individuals with spinal cord injury.

STUDY DESIGN: Cross-sectional. OBJECTIVES: Individualized training regimes are often based on ventilatory thresholds (VTs). The objectives were to study: (1) whether VTs during arm ergometry could be determined in individuals with spinal cord injury (SCI), (2) the intrarater and interrater reliability of VT determination. SETTING: University research laboratory. METHODS: Thirty graded arm crank ergometry exercise tests with 1-min increments of recreationally active individuals (tetraplegia (N = 11), paraplegia (N = 19)) were assessed. Two sports physicians assessed all tests blinded, randomly, in two sessions, for VT1 and VT2, resulting in 240 possible VTs. Power output (PO), heart rate (HR), and oxygen uptake (VO2) at each VT were compared between sessions or raters using paired samples t-tests, Wilcoxon signed-rank tests, intraclass correlation coefficients (ICC, relative agreement), and Bland-Altman plots (random error, absolute agreement). RESULTS: Of the 240 VTs, 217 (90%) could be determined. Of the 23 undetermined VTs, 2 (9%) were VT1 and 21 (91%) were VT2; 7 (30%) among individuals with paraplegia, and 16 (70%) among individuals with tetraplegia. For the successfully determined VTs, there were no systematic differences between sessions or raters. Intrarater and interrater ICCs for PO, HR, and VO2 at each VT were high to very high (0.82-1.00). Random error was small to large within raters, and large between raters. CONCLUSIONS: For VTs that could be determined, relative agreement was high to very high, absolute agreement varied. For some individuals, often with tetraplegia, VT determination was not possible, thus other methods should be considered to prescribe exercise intensity.

Comparison of 1- Versus 3-Minute Stage Duration During Arm Ergometry in Individuals With Spinal Cord Injury.

OBJECTIVE: To investigate the effect of stage duration on peak physiological response to arm ergometry incremental exercise testing in individuals with spinal cord injury or disease (SCI/D) in support of developing a more individualized approach to testing. DESIGN: Parallel reliability study. SETTING: University research laboratory. PARTICIPANTS: Individuals with SCI/D (N=38) performed 2 peak oxygen consumption assessments comprised of 1-minute or 3-minute stages on 1 day. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Heart rate and oxygen consumption were recorded continuously from baseline through recovery. Every 1 minute or 3 minutes, resistance increased at an individualized level, and participants continued until volitional fatigue. The highest 30-second average was selected as peak oxygen consumption (Vo2peak) and peak heart rate. The highest workload achieved for ≥30 seconds was recorded as peak power output (PO). RESULTS: Intraclass correlation coefficients (ICCs) were >.95 for the following variables: absolute Vo2peak (mean ± SD, 1min: 1.2±0.7, 3min: 1.2±.62L/min; 95% CI, .91-.98), relative Vo2peak (mean ± SD, 1min: 16.6±9.4, 3min: 15.8±8.0mL/kg/min; 95% CI, .90-.98), absolute peak PO (mean ± SD, 1min: 61±41, 3min: 66±41W; 95% CI, .92-.98), and relative peak PO (mean ± SD, 1min: .80±56, 3min: .90±.55W/kg; 95% CI, .91-.98). There was no significant difference in peak heart rate between 3 minutes (132±27 beats per minute [bpm]) and 1 minute (130±28 bpm); however, the ICC lower limit was <.75 (0.67-0.90). Total test time was significantly longer in the 3-minute (8:17±2:52min:s) than in the 1-minute (6:29±2:21min:s) protocol. CONCLUSIONS: For measuring peak physiological values in an incremental arm ergometry test, stage duration is of little consequence because similar values were obtained for the main outcome measures in both protocols.

Feasibility study of high-intensity interval training to reduce cardiometabolic disease risks in individuals with acute spinal cord injury.

INTRODUCTION: Individuals ageing with spinal cord injury (SCI) experience an accelerated trajectory of diseases and disorders, such as cardiovascular disease and diabetes, that resemble those experienced with ageing alone. Currently, an evidence-based approach toward managing this problem does not exist and therefore the purpose of this study is to determine the feasibility of conducting a high-intensity exercise intervention in individuals with acute (<6 months postinjury) SCI to improve cardiometabolic health. METHODS AND ANALYSIS: We will conduct a single-centre, two parallel-arm, randomised feasibility study of a high-intensity interval training (HIIT) intervention in individuals with acute SCI. We will enrol 40 individuals (20 intervention, 20 control) with acute SCI attending inpatient rehabilitation at Salisbury District Hospital. Participants will be randomly allocated to the intervention group (HIIT) or control group for 18 weeks. Both groups will participate in standard care throughout the duration of the study. The HIIT group only will also perform supervised HIIT exercise on an arm cycle ergometer three times per week. Over the course of the intervention, most participants will be discharged from the hospital, and at this time, an arm cycle ergometer will be installed in their home and the intervention will transition into outpatient care. We will assess cardiorespiratory fitness, glycaemic control, lipid profile and body habitus as well as qualitative assessments of acceptability at weeks 0, 9 and 18 with the primary outcome being the feasibility of a full Randomised Controlled Trial (RCT). ETHICS AND DISSEMINATION: This study will inform a longer-term, definitive, multicentre RCT to establish the impact of this exercise intervention in maintaining the cardiometabolic health of patients during the acute phase following SCI. Results will be disseminated in different formats including peer-reviewed journal articles, conference presentations and internet media, to a wide audience including clinicians, researchers and individuals with SCI. TRIAL REGISTRATION NUMBER: ISRCTN57514022.

Exercise Interventions Targeting Obesity in Persons With Spinal Cord Injury.

Spinal cord injury (SCI) results in an array of cardiometabolic complications, with obesity being the most common component risk of cardiometabolic disease (CMD) in this population. Recent Consortium for Spinal Cord Medicine Clinical Practice Guidelines for CMD in SCI recommend physical exercise as a primary treatment strategy for the management of CMD in SCI. However, the high prevalence of obesity in SCI and the pleiotropic nature of this body habitus warrant strategies for tailoring exercise to specifically target obesity. In general, exercise for obesity management should aim primarily to induce a negative energy balance and secondarily to increase the use of fat as a fuel source. In persons with SCI, reductions in the muscle mass that can be recruited during activity limit the capacity for exercise to induce a calorie deficit. Furthermore, the available musculature exhibits a decreased oxidative capacity, limiting the utilization of fat during exercise. These constraints must be considered when designing exercise interventions for obesity management in SCI. Certain forms of exercise have a greater therapeutic potential in this population partly due to impacts on metabolism during recovery from exercise and at rest. In this article, we propose that exercise for obesity in SCI should target large muscle groups and aim to induce hypertrophy to increase total energy expenditure response to training. Furthermore, although carbohydrate reliance will be high during activity, certain forms of exercise might induce meaningful postexercise shifts in the use of fat as a fuel. General activity in this population is important for many components of health, but low energy cost of daily activities and limitations in upper body volitional exercise mean that exercise interventions targeting utilization and hypertrophy of large muscle groups will likely be required for obesity management.

The Relationship between HIV Duration, Insulin Resistance and Diabetes Risk.

The risk of developing Type 2 Diabetes Mellitus in people living with HIV (PLWH) can be four times greater and can occur at an earlier age and even without the presence of obesity compared to those without HIV. Therefore, the purpose of this analytical cross-sectional study was to determine the relationship between HIV duration and glucose metabolism among PLWH. Eighty-two PLWH were categorized into shorter (≤15 years) or longer HIV duration (≥16 years) and then compared for differences in demographics, physical and clinical characteristics, biomarkers, and dietary intake. Compared to those with shorter HIV duration (n = 34), those with longer HIV duration (n = 48) were on average older (p = 0.02), reported lower consumption of alcohol (p = 0.05), had higher levels of homeostasis model assessment of insulin resistance (HOMA-IR, p = 0.02), were also more likely to be a woman (p = 0.06), and have higher levels of fasting insulin (p = 0.06). When adjusted for age and body weight, the levels of HOMA-IR and fasting insulin were higher (p = 0.02 and p = 0.04) with longer compared to shorter HIV duration, respectively. Longer exposure to HIV infection is associated with impaired insulin sensitivity. Continuing research aimed at the long-term effects of HIV infection and (antiretroviral therapy) is required.

A Single Bout of Upper-Body Exercise Has No Effect on Postprandial Metabolism in Persons with Chronic Paraplegia.

PURPOSE: The acute effects of a single bout of upper-body exercise on postprandial metabolism in persons with spinal cord injury are currently not well understood. The primary aim of this study was to evaluate the effects of a single bout of upper-body high-intensity interval exercise (HIIE) and moderate-intensity continuous exercise (MICE) in comparison with a no-exercise control (REST) condition on postprandial metabolic responses in persons with chronic paraplegia. METHODS: Ten participants (eight males, two females; age, 49 ± 10 yr; time since injury, 22 ± 13 yr) with chronic paraplegia took part in a randomized crossover study, consisting of three trials: HIIE (8 × 60 s at 70% peak power output [PPEAK]), MICE (25 min at 45% PPEAK), and REST, at least 3 d apart. Exercise was performed in the fasted state, and participants consumed a mixed-macronutrient liquid meal 1-h postexercise. Venous blood and expired gas samples were collected at regular intervals for 6-h postmeal consumption. RESULTS: There were no significant differences in postprandial incremental area under the curve for triglycerides (P = 0.59) or glucose (P = 0.56) between conditions. Insulin incremental area under the curve tended to be lower after MICE (135 ± 85 nmol·L-1 per 360 min) compared with REST (162 ± 93 nmol·L-1 per 360 min), but this did not reach statistical significance (P = 0.06, d = 0.30). Participants reported a greater fondness (P = 0.04) and preference for HIIE over MICE. CONCLUSIONS: After an overnight fast, a single bout of upper-body exercise before eating has no effect on postprandial metabolism in persons with chronic paraplegia, irrespective of exercise intensity. This suggests that alternative exercise strategies may be required to stimulate postprandial substrate oxidation for this population.

Effects of Exercise Mode on Postprandial Metabolism in Humans with Chronic Paraplegia.

PURPOSE: The purpose of this study was to assess the acute effects of exercise mode and intensity on postprandial macronutrient metabolism. METHODS: Ten healthy men age 39 ± 10 yr with chronic paraplegia (13.2 ± 8.8 yr, ASIA A-C) completed three isocaloric bouts of upper-body exercise and a resting control. After an overnight fast, participants completed circuit resistance exercise (CRE) first and the following conditions in a randomized order, separated by >48 h: i) control (CON), ~45-min seated rest; ii) moderate-intensity continuous exercise (MICE), ~40-min arm cranking at a resistance equivalent to ~30% peak power output (PPO); and iii) high-intensity interval exercise (HIIE), ~30 min arm cranking with resistance alternating every 2 min between 10% PPO and 70% PPO. After each condition, participants completed a mixed-meal tolerance test consisting of a 2510-kJ liquid meal (35% fat, 50% carbohydrate, 15% protein). Blood and expired gas samples were collected at baseline and regular intervals for 150 min after a meal. RESULTS: An interaction (P < 0.001) was observed, with rates of lipid oxidation elevated above CON in HIIE until 60 min after a meal and in CRE at all postprandial time points up to 150 min after a meal. Postprandial blood glycerol was greater in MICE (P = 0.020) and CRE (P = 0.001) compared with CON. Furthermore, nonesterified fatty acid area under the curve had a moderate-to-strong effect in CRE versus MICE and HIIE (Cohen's d = -0.76 and -0.50, respectively). CONCLUSIONS: In persons with paraplegia, high-intensity exercise increased postprandial energy expenditure independent of the energy cost of exercise. Furthermore, exercise combining resistance and endurance modes (CRE) showed the greater effect on postprandial lipid oxidation.

Neither Postabsorptive Resting Nor Postprandial Fat Oxidation Are Related to Peak Fat Oxidation in Men With Chronic Paraplegia.

The peak rate of fat oxidation (PFO) achieved during a graded exercise test is an important indicator of metabolic health. In healthy individuals, there is a significant positive association between PFO and total daily fat oxidation (FO). However, conditions resulting in metabolic dysfunction may cause a disconnect between PFO and non-exercise FO. Ten adult men with chronic thoracic spinal cord injury (SCI) completed a graded arm exercise test. On a separate day following an overnight fast (≥ 10 h), they rested for 60 min before ingesting a liquid mixed meal (600 kcal; 35% fat, 50% carbohydrate, 15% protein). Expired gases were collected and indirect calorimetry data used to determine FO at rest, before and after feeding, and during the graded exercise test. Participants had "good" cardiorespiratory fitness (VO2peak: 19.2 ± 5.2 ml/kg/min) based on normative reference values for SCI. There was a strong positive correlation between PFO (0.30 ± 0.08 g/min) and VO2peak (r = 0.86, p = 0.002). Additionally, postabsorptive FO at rest was significantly and positively correlated with postprandial peak FO (r = 0.77, p = 0.01). However, PFO was not significantly associated with postabsorptive FO at rest (0.08 ± 0.02 g/min; p = 0.97), postprandial peak FO (0.10 ± 0.03 g/min; p = 0.43), or incremental area under the curve postprandial FO (p = 0.22). It may be advantageous to assess both postabsorptive FO at rest and PFO in those with SCI to gain a more complete picture of their metabolic flexibility and long-term metabolic health.

Influence of upper-body continuous, resistance or high-intensity interval training (CRIT) on postprandial responses in persons with spinal cord injury: study protocol for a randomised controlled trial.

BACKGROUND: Chronic spinal cord injury (SCI) increases morbidity and mortality associated with cardiometabolic diseases, secondary to increases in central adiposity, hyperlipidaemia and impaired glucose tolerance. While upper-body Moderate Intensity Continuous Training (MICT) improves cardiorespiratory fitness, its effects on cardiometabolic component risks in adults with SCI appear relatively modest. The aim of this study is to assess the acute effects of Continuous Resistance Training (CRT), High Intensity Interval Training (HIIT), MICT and rest (CON) on fasting and postprandial systemic biomarkers and substrate utilisation. METHODS: Eleven healthy, chronic SCI (> 1 year, ASIA A-C) men will be recruited. Following preliminary testing, each will complete four experimental conditions, where they will report to the laboratory following an ~ 10-h overnight fast. A venous blood sample will be drawn and expired gases collected to estimate resting metabolic rate (RMR). In order to ensure an isocaloric exercise challenge, each will complete CRT first, with the remaining three conditions presented in randomised order: (1) CRT, ~ 45 min of resistance manoeuvres (weight lifting) interspersed with low-resistance, high-speed arm-crank exercise; (2) CON, seated rest; (3) MICT, ~ 45 min constant arm-crank exercise at a resistance equivalent to 30-40% peak power output (PPO) and; (4) HIIT, ~ 35 min arm-crank exercise with the resistance alternating every 2 min between 10% PPO and 70% PPO. After each ~ 45-min condition, participants will ingest a 2510-kJ liquid test meal (35% fat, 50% carbohydrate, 15% protein). Venous blood and expired gas samples will be collected at the end of exercise and at regular intervals for 120 min post meal. DISCUSSION: This study should establish the acute effects of different forms of exercise on fasting and postprandial responses in chronic SCI male patients. Measures of glucose clearance, insulin sensitivity, lipid and inflammatory biomarker concentrations will be assessed and changes in whole-body substrate oxidation estimated from expired gases. TRIAL REGISTRATION: ClinicalTrials.gov, ID: NCT03545867 . Retrospectively registered on 1 June 2018.

Exercise and Health-Related Risks of Physical Deconditioning After Spinal Cord Injury.

A sedentary lifestyle occurring soon after spinal cord injury (SCI) may be in contrast to a preinjury history of active physical engagement and is thereafter associated with profound physical deconditioning sustained throughout the lifespan. This physical deconditioning contributes in varying degrees to lifelong medical complications, including accelerated cardiovascular disease, insulin resistance, osteopenia, and visceral obesity. Unlike persons without disability for whom exercise is readily available and easily accomplished, exercise options for persons with SCI are more limited. Depending on the level of injury, the metabolic responses to acute exercise may also be less robust than those accompanying exercise in persons without disability, the training benefits more difficult to achieve, and the risks of ill-considered exercise both greater and potentially irreversible. For exercise to ultimately promote benefit and not impose additional impairment, an understanding of exercise opportunities and risks if exercise is undertaken by those with SCI is important. The following monograph will thus address common medical challenges experienced by persons with SCI and typical modes and benefits of voluntary exercise conditioning.

Clinician-Focused Overview of Bionic Exoskeleton Use After Spinal Cord Injury.

Spinal cord injury (SCI) resulting in paralysis of lower limbs and trunk restricts daily upright activity, work capacity, and ambulation ability, putting persons with an injury at greater risk of developing a myriad of secondary medical issues. Time spent in the upright posture has been shown to decrease the risk of these complications in SCI. Unfortunately, the majority of ambulation assistive technologies are limited by inefficiencies such as high energy demand, lengthy donning and doffing time, and poor gait pattern precluding widespread use. These limitations spurred the development of bionic exoskeletons. These devices are currently being used in rehabilitation settings for gait retraining, and some have been approved for home use. This overview will address the current state of available devices and their utility.

Ischemic preconditioning does not improve peak exercise capacity at sea level or simulated high altitude in trained male cyclists.

Ischemic preconditioning (IPC) may improve blood flow and oxygen delivery to tissues, including skeletal muscle, and has the potential to improve intense aerobic exercise performance, especially that which results in arterial hypoxemia. The aim of the study was to determine the effects of IPC of the legs on peak exercise capacity (W(peak)), submaximal and peak cardiovascular hemodynamics, and peripheral capillary oxygen saturation (SpO2) in trained males at sea level (SL) and simulated high altitude (HA; 13.3% FIO2, ∼ 3650 m). Fifteen highly trained male cyclists and triathletes completed 2 W(peak) tests (SL and HA) and 4 experimental exercise trials (10 min at 55% altitude-specific W(peak) then increasing by 30 W every 2 min until exhaustion) with and without IPC. HA resulted in significant arterial hypoxemia during exercise compared with SL (73% ± 6% vs. 93% ± 4% SpO2, p < 0.001) that was associated with 21% lower W(peak) values. IPC did not significantly improve W(peak) at SL or HA. Additionally, IPC failed to improve cardiovascular hemodynamics or SpO2 during submaximal exercise or at W(peak). In conclusion, IPC performed 45 min prior to exercise does not improve W(peak) or systemic oxygen delivery during submaximal or peak exercise at SL or HA. Future studies must examine the influence of IPC on local factors, such as working limb blood flow, oxygen delivery, and arteriovenous oxygen difference as well as whether the effectiveness of IPC is altered by the volume of muscle made ischemic, the timing prior to exercise, and high altitude acclimatization.