IntroductionIt is well established that young people with moderate-severe (Gross Motor Function Classification System [GMFCS] levels II-V) cerebral palsy (CP) participate in less physical activity compared to typically developed peers, and children with CP who can walk without limitations (GMFCS level I). Frame Running (formerly RaceRunning) is a World Para Athletics sanctioned sport that allows people with moderate-severe CP to access, experience and compete in running using a specialised three-wheeled frame with low rolling resistance. The Run4Health pilot randomised controlled trial (protocol published elsewhere) was designed to investigate the cardiorespiratory benefits of a 12-week frame running training program in young people with CP (aged 8-21 years, GMFCS II-V). Following enrolment of 12 participants in the pilot study, additional funding was secured to expand the Run4Health study to include additional training/study sites, new research questions and outcome measures, based on feedback from consumers. Such changes necessitate an expanded and updated study protocol. This expanded Run4Health study will investigate the effects of a 12- week Frame Running training program on cardiorespiratory health, bone mineral density, gross motor function and capacity, physical activity participation, sleep, pain and quality of life in children and youth (aged 8-21 years) with moderate-severe CP (GMFCS levels II-V).Methods and AnalysisOne hundred and two children and youth with CP (age 8-21 years) classified in GMFCS levels II-V will be recruited across three sites (six training locations) and randomised to receive either 12 weeks of Frame Running training twice weekly for 60 minutes, or 12 weeks of usual care (waitlist control group). Outcomes will be measured at baseline, immediately post-intervention, and 12 weeks post-intervention. The control group will receive the intervention following T3, and have an additional assessment session following 12 weeks of training (T4). Outcomes include cardiorespiratory fitness, bone mineral density, blood pressure, habitual physical activity, body mass index, waist circumference, percentage body fat, gross motor function and capacity, community participation, sleep, pain, quality of life and mood, health utility, feasibility, tolerability, and safety. Adverse events will be monitored, and participants, caregivers and coaches will be interviewed to explore barriers and facilitators to ongoing, sustainable participation in Frame Running.Ethics and DisseminationEthical approval for this study was granted by The Children’s Health Queensland Hospital and Health Service (HREC/21/QCHQ/69281) and the University of Queensland Human Research Ethics Committees (2021/HE000725). Research outcomes will be disseminated via scientific conferences and publications in peer reviewed journals; to therapists and coaches through professional and athletic organisations; and to people with CP and their families.RegistrationAustralian New Zealand Clinical Trials Registry number: ACTRN12621000317897