The Effects of a Hybrid HIIT-FES Cycling Program on Individuals With Spinal Cord Injury to Improve Cardiovascular and Metabolic Health

Specific Aims: Obesity and cardiometabolic disorders are epidemic among people with spinal cord injury (SCI). A recent study conducted on a large cohort of individuals with chronic SCI revealed that 90% of them were obese, and 60% suffered from metabolic syndrome, which includes dyslipidemia, hyperglycemia, and hypertension along with obesity. This health disparity is even worse for those living with SCI in Mississippi, a perennial national leader in the prevalence of obesity and cardiometabolic disease. These data indicate that individuals with SCI are on an accelerated trajectory toward cardiometabolic disease and early mortality. This accelerated trajectory is multi-factorial, but substantial evidence suggests low physical activity is a significant contributing factor. Paralysis combined with a sedentary lifestyle leads to individuals with SCI experiencing significant changes in body composition with evidence of increased fat mass and a reduction in lean mass. The investigators recently reported that the ratio of fat to lean mass was a strong predictor of systemic inflammation and cardiometabolic disorders in individuals with SCI. Since medical advancements are increasing survival and longevity after SCI, it is critical to develop programs and establish best-practice interventions aimed at decreasing obesity and cardiometabolic disease risk in the SCI population.

Although arm exercises have some benefits, they do not engage the large muscle groups of the legs, which limits muscle participation. However, leg cycling with functional electrical stimulation (FES) has been found to be a safe and effective way to exercise paralyzed leg muscles. This can lead to muscle hypertrophy and an improved lean mass to fat mass ratio. To prevent cardiometabolic diseases, it is important to recruit adequate muscle mass at high enough intensity levels to induce central and peripheral physiological training adaptations. Combining the paralyzed leg muscles through FES with voluntary arm muscle activity (hybrid exercise) will increase overall muscle involvement and exercise intensity, potentially improving cardiometabolic health.

The investigators have developed a novel hybrid high-intensity interval training (HIIT) protocol that combines FES lower extremity cycling and voluntary arm cycling in a HIIT protocol for individuals with SCI. This hybrid HIIT-FES cycling program is designed to incorporate greater muscle mass into the activity. HIIT training programs have been shown to provide equal or more significant benefits with less time commitment in the general population. Our proof-of-principle studies in persons with SCI confirmed that HIIT-FES leg cycling three times per week for eight weeks can increase leg lean mass (5-9%) and improve cardiovascular health markers. However, some participants could not cycle against greater than the default resistance until after 12 sessions, even with the maximum electrical stimulation. For this reason, our intervention protocol will be in two phases, with phase one consisting of peripheral remodeling intermittent muscular exercise (PRIME) two times per week for four weeks. This resistance training part of the program prepares the participants for phase two, which is the hybrid HIIT-FES cycling program twice weekly for eight weeks. Exercise sessions will last 30 to 40 minutes, depending on the participants' tolerance. We will recruit twelve adults, 21-70 years of age, with chronic SCI ranging in neurological level between C4-T12 and maintaining the ability to perform arm cycling (incomplete injuries C4-T1). Participants will be randomly divided into the hybrid HIIT-FES group (n=6) or the control group (n=6) (active range of motion exercise with arms and passive with the legs). Research AIM: The purpose of this study is to determine the effectiveness of four-weeks of PRIME resistance training followed by eight weeks of hybrid HIIT-FES cycling on adults with SCI. The goal is to provide new insights into developing exercise programs for individuals with SCI. The investigators specific hypothesis is that a twice-weekly PRIME plus hybrid HIIT-FES cycling program will lead to significant improvements in aerobic fitness, lean mass to fat mass ratio, blood lipid and glucose levels, inflammation markers, muscle oxygenation, and physical transfers and wheelchair propulsion. This study aligns with the mission of the Mississippi IDeA Network of Biomedical Research Excellence by providing valuable information about the battle against obesity and cardiometabolic disease in a highly vulnerable and at-risk population. The findings from this pilot study are expected to serve as preliminary data for further, in-depth research.

Research Strategy Significance: Approximately 18,000 accidents lead to spinal cord injury (SCI) in the U.S. annually. Life span after SCI was previously short, but thanks to medical advances, SCI has been converted to a long-term chronic disability. Consequently, increased longevity in this population has been accompanied by many adverse health conditions, with obesity and cardiometabolic diseases being at the forefront of health disparities. Obesity prevalence among individuals with SCI is about 90%. Additionally, because greater obesity is related to greater disability and chronic diseases, the risk of cardiometabolic diseases, including heart disease and type II diabetes, is elevated to more than twice that of the able-bodied population. One reason for high obesity after SCI is the loss of muscle mass. Shortly after the injury, those with SCI experience rapid and significant skeletal muscle atrophy below the level of injury, resulting in skeletal muscle cross-sectional areas of 45-80% less than that of able-bodied individuals. Therefore, after SCI, the loss of metabolically active muscle mass results in a 26% reduction in basal metabolic rate and resting energy expenditure. This is important because basal metabolic rate accounts for ~65% of the total daily energy expenditure and plays a major role in the positive energy balance that results in obesity after SCI. In addition to decreased muscle mass individuals with SCI are typically among the most sedentary. This adds to the creation of an unhealthy energy balance as well as deconditioning of major organ systems such as the cardiovascular and musculoskeletal systems.

Given these circumstances, it is important to develop exercise programs capable of increasing energy expenditure via increased physical activity, reversing the loss of muscle mass and improving the cardiometabolic health in people with SCI. The benefits of physical activity for reducing obesity and cardiometabolic disease have been well documented. In particular, high-intensity interval training (HIIT) has been shown to decrease cardiovascular and metabolic risk among able-bodied individuals in a shorter period of time than standard non-interval exercise programs. For example, compared interval walking, continuous walking in able-bodied adults with type II diabetes over a six month period. The continuous walking group walked for 60 minutes five days per week at a moderate intensity while the interval training group alternated between three minutes of high intensity walking and three minutes of low intensity walking five days per week. The walking intensities were determined by oxygen uptake (VO2peak) testing and energy expenditure, with moderate intensity being set at 55% and high intensity at 70% of VO2peak. Although, the mileage was the same for both groups, the interval training group lost 4.3 ± 1.2 kg total body weight and 3.1 ± 0.7 kg body fat mass, whereas no changes in body composition were found in the continuous walking group or the non-walking control group. In a similar study, using leg cycling three times per week for 12 weeks in both the continuous and interval groups and determined intensity levels based on heart rate. The interval training group performed three "all out" cycling sessions of 20 seconds each separated by two minutes low intensity cycling, while the continuous group cycled steady at 70% of maximal heart rate for 45 minutes. Both groups improved similarly in insulin sensitivity, cardiorespiratory fitness, and skeletal muscle mitochondrial content, however, the interval training group achieved these benefits with a five-fold lower exercise volume and training time commitment.