Project Summary/Abstract For the more than 5.5 million people in the U.S. who use wheelchairs as their primary mode of ambulation, there is a pervasive lack of research on reducing cardiometabolic risk through structured exercise. Confirmatory analyses have revealed that wheelchair users live predominantly sedentary lifestyles and have substantially higher cardiometabolic risk factors compared to the general population. Although few exercise training studies have investigated cardiometabolic risk in certain subgroups with a disability, small sample sizes and homogeneous groups limit the translatability of this knowledge into clinical practice risk reduction strategies for wheelchair users. To address these issues, we propose to use a robust remote training system with built-in videoconferencing and real-time monitoring of vital sign data (e.g., heart rate, respiratory rate). This procedure will allow us to examine the efficacy of an evidence-based Movement-to-Music (M2M) program adapted for telehealth delivery and cardio emphasis (M2M-C). We are proposing a two-arm randomized controlled trial including 132 wheelchair users with a poor cardiometabolic profile (e.g., elevated triglycerides) recruited through our established network of clinics serving this population. The long-term goal of this proposal is to develop an effective and enjoyable modality for promoting health-enhancing exercise for wheelchair users by confirming exercise dose requirements for this underrepresented group. The primary aim will examine the average treatment effects of a 24-week M2M-C program on core indicators of CMH in wheelchair users with ≥ 2 cardiometabolic risk factors. CMH outcomes will be measured via blood tests (i.e., high sensitivity C-reactive protein, hemoglobin, fasting insulin, triglycerides, and cholesterol) and DEXA scan (i.e., body composition) at baseline and after 12 and 24 weeks of synchronous M2M-C training. The secondary aim will explore the beneficial effects of M2M-C on cardiovascular capacity, physical activity, and quality of life. Cardiovascular capacity will be measured via peak oxygen consumption. Physical activity and quality of life will be measured by self-report instruments validated for this population. The tertiary aim 1 is to evaluate the sustained effects of M2M-C (24 to 36 weeks) on physical activity. After M2M participants complete the 24-week program, they will be instructed to perform asynchronous exercise training using guided M2M online videos for an additional 12 weeks. The tertiary aim 2 is to examine the heterogeneity of treatment effect (HTE), which aims to understand whom the intervention is most effective.