Forced-rate aerobic cycling enhances motor recovery in persons with chronic stroke: A randomized clinical trial

Background: The potential for intensive aerobic exercise to enhance neuroplasticity post-stroke has been theorized but not systematically investigated. Our aim was to determine the effects of forced-rate aerobic exercise paired with an abbreviated session of upper extremity (UE) repetitive task practice (FE+RTP) compared to time-matched UE repetitive task practice (RTP only) on the recovery of motor function in individuals with chronic stroke. Methods: A single center randomized clinical trial was conducted from April 2019 to December 2022. Sixty individuals ≥6 months following single stroke with residual UE hemiparesis aged 18-85 were recruited. Participants were randomized 1:1 to one of two time-matched groups: FE+RTP (N=30) or RTP only (N=30). Both groups completed 90-minute sessions, 3x/week for 8 weeks. The FE+RTP group underwent 45-minutes of forced-rate aerobic exercise (FE) followed by 45-min of UE RTP. The RTP only group completed 2 sequential 45-minute sessions of UE RTP. The primary UE outcomes were the Fugl-Meyer Assessment (FMA) and the Action Research Arm Test (ARAT). The Six-minute Walk Test (6MWT) assessed walking capacity. Results: Sixty individuals 60.5 (±10.6) years of age and 26.0 [13.0, 69.0] months post-stroke were enrolled, and 56 completed the study. The RTP only group completed more RTP in terms of repetitions (411.8±44.4 versus 222.8±28.4, P<0.001) and time (72.7±6.7 versus 37.8±2.4 minutes, P<0.001) compared to FE+RTP. Both groups improved on the FMA (FE+RTP, 36.2±10.1 to 44.0±11.8 and RTP only, 34.4±11.0 to 41.2±13.4, P<0.001) and ARAT (FE+RTP, 32.5±16.6 to 37.7±17.9 and RTP only, 32.8±18.6 to 36.4±18.5, P<0.001). A group main effect was not observed. The FE+RTP group demonstrated greater improvements on the 6MWT (274.9±122.0 to 327.1±141.2 meters) compared to the RTP only group (285.5±160.3 to 316.9±170.0, P=0.004). Conclusions While both interventions elicited comparable improvements in UE motor recovery, the summative value of FE+RTP in improving UE and lower extremity function was demonstrated. Trial Registration: [ClinicalTrials.gov][1]: [NCT03819764][2] ### Competing Interest Statement Dr. Alberts has authored intellectual property protecting the forced-rate exercise cycle algorithm. ### Clinical Trial [ClinicalTrials.gov][1]: [NCT03819764][2] ### Funding Statement The trial was funded by the National Institutes of Health (K01HD092556). ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: The Cleveland Clinic IRB approved this study. IRB# 18-743. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as [ClinicalTrials.gov][1]. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes An application is pending to submit data from this trial to the NIH DASH database. [1]: http://ClinicalTrials.gov [2]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT03819764&atom=%2Fmedrxiv%2Fearly%2F2023%2F08%2F07%2F2023.08.02.23293572.atom