The goal of this clinical trial is to learn whether combining moderate to high intensity aerobic exercise with constraint-induced movement therapy (CI therapy) can improve walking ability in adults who have had a stroke. The study will also learn if telerehabilitation at home can support long-term recovery after intensive rehabilitation.

The main questions this study aims to answer are:

• Does moderate to high intensity aerobic exercise before CI therapy improve walking ability, balance and lower extremity function in people with long-lasting gait difficulties after stroke?
• Does CI therapy alone lead to similar or different improvements in walking ability, balance or lower extremity function?
• Does telerehabilitation help participants maintain or further improve their function after the intensive rehabilitation period?

Researchers will compare two groups. One group will receive 4 weeks of CI therapy, 5 days per week, plus 20 minutes of moderate-to-high-intensity aerobic exercise before the rehabilitation session on 3 of these days, and the other group will receive 4 weeks of CI therapy, 5 days per week, without preparatory aerobic exercise.

After the completion of CI therapy, all participants will be offered an individualized 8-week telerehabilitation program to follow at home. They will use a mobile application to report physical activity and follow instructions for telerehabilitation.

All participants will complete two assessment visits (about 3 hours each), 1-2 weeks before and 1-2 weeks after CI therapy. They will also complete questionnaires electronically after the telerehabilitation program.

Daily activity will be measured twice during the study: once during a week after the intensive rehabilitation and once during a week after the telerehabilitation program. A small movement sensor worn on the thigh will be used. The sensor is attached with a soft strap or an adhesive patch and is comfortable to wear all day. The sensor shows how much a person walks, stands, or sits in everyday life. It is light, does not disturb normal activities, and only collects movement information for the study. An instruction sheet will be included to make it easy to use.

This study will use a two-arm, cluster-randomised experimental design to investigate whether lower-extremity modified constraint-induced movement therapy (LE-mCIMT) is more effective when combined with moderate-to-high-intensity aerobic exercise.

A total of 50 stroke survivors will be recruited. All participants will have experienced a stroke at least 6 months earlier and present with persistent gait impairments. Eligible individuals must have been referred for intensive CI therapy at Neurocampus, Sophiahemmet, or at the rehabilitation clinic Furuhöjden in Stockholm, and must have been assessed as medically suitable for intensive training by a responsible physician.

All assessments, baseline and post-intervention, will be conducted at the Laboratory for Applied Sport Science (LTIV) at the Swedish School of Sport and Health Sciences (GIH) in Stockholm, with remote data collection via a digital platform and an activity monitor.

Participants will be allocated to the two intervention arms via cluster randomisation within their rehabilitation cohort. The rehabilitation program is organised in groups of five patients per 4-week block. Eligible participants within the same rehabilitation cohort will be treated as a single cluster to prevent contamination between intervention types. Because members of the same cohort train together daily, share therapists, and interact closely throughout the program, individual randomisation within a cohort could lead to cross-influence and dilution of treatment effects. To avoid this, each rehabilitation cohort (cluster) will be randomised to one of two conditions:

1. LE-mCIMT-EXE, consisting of LE-mCIMT combined with moderate-to-high intensity aerobic exercise, or
2. LE-mCIMT-TAU, consisting of LE-mCIMT delivered according to standard treatment procedures without additional aerobic exercise.

The intervention period for both arms consists of a 4-week program delivered five days per week.

Participants in the LE-mCIMT-EXE group will perform a 20-minute session of moderate-to-high intensity aerobic exercise immediately before therapy on three days per week, followed by their daily LE-mCIMT session. Exercise will be performed on a recumbent total-body stepper or an ergometer cycle. Heart rate will be continuously monitored with a chest-strap sensor, and exertion will be rated on the Borg RPE scale. Exercise intensity will be individually adjusted to ensure a safe and appropriate cardiovascular load. The total duration will be approximately 12 minutes of active work plus warm-up and cool-down, totaling 20 minutes.

Participants in the LE-mCIMT-TAU group will complete the same LE-mCIMT schedule without the aerobic exercise component.

The LE-mCIMT intervention is designed to promote functional improvement of the affected lower limb through intensive, task-specific training. Each session incorporates repetitive task practice, shaping techniques, functional mobility exercises, and gait and weight-bearing activities. This structured, high-frequency approach is intended to enhance neuroplasticity and support improvements in gait performance and lower-limb motor control. Therapists will adjust task difficulty according to individual performance to maintain an optimal challenge level. The LE-mCIMT protocol and all delivery procedures will be standardised across participating sites, including Neurocampus and Furuhöjden, to ensure consistency in treatment exposure.

After completing the 4-week intervention, all participants will be offered an 8-week telerehabilitation program tailored to their individual needs.

Data collection timeline: All participants will undergo assessments at two in-person visits at LTIV, as well as remote follow-up during telerehabilitation.

Visit 1 will take place one to two weeks before the start of the LE-mCIMT program and will require about three hours to complete. During this visit, participants will receive detailed information about the study procedures, after which they will provide informed consent. A lifestyle and health screening will then be conducted, including assessment of demographic and general health information, smoking habits, medication use, physical activity level, and occupational or educational status. Blood pressure will also be measured during the initial screening.

Participants will complete a set of questionnaires, including a health declaration, the Stroke Impact Scale (SIS), the Hospital Anxiety and Depression Scale (HADS), and the Swedish version of the Exercise Self-Efficacy Scale. Following completion of the questionnaires, a series of functional assessments will be performed. Motor function will be evaluated using the Fugl-Meyer Assessment for the lower extremity (LE-FMA), and dynamic balance will be assessed using the Mini Balance Evaluation Systems Test (Mini-BESTest). Gait speed will be measured through the 10-Meter Walk Test (10MWT), and gait endurance will be assessed using the 6-Minute Walk Test (6MWT). Cognitive status will be evaluated using the Montreal Cognitive Assessment (MoCA).

Blood samples will be collected to analyze platelet levels using automated laboratory systems, as well as plasma and serum concentrations of various biological markers. These analyses will include myokines, neurotrophic factors, neuroinflammatory markers, neurodegenerative markers, and vascular-related factors such as BDNF, proBDNF, VEGF, NFL, and GFAP. Analyses will be conducted using ELISA or SIMOA technology. DNA testing for BDNF alleles will also be performed. If blood sampling is not feasible, saliva samples will be collected for allele determination. Together, these measures will provide a comprehensive baseline profile of participants' physical, functional, cognitive, and biological status prior to the intervention.

Finally, participants will perform a submaximal aerobic capacity test. The test will be conducted using either a recumbent total-body stepper or an ergometer cycle, depending on the participant's functional abilities and safety considerations. Throughout the test, heart rate will be monitored continuously using a validated chest-strap sensor to ensure an appropriate and safe physiological response. Participants will also be asked to report their perceived exertion at regular intervals using the Borg Rating of Perceived Exertion (RPE) scale.

The active portion of the test will last approximately 12 minutes. Workload intensity will be individually adjusted based on each participant's cardiovascular response, aiming to achieve a controlled, consistent submaximal effort. This individualised approach allows the assessment to accurately reflect aerobic capacity while minimising physical strain and ensuring participant safety.

Visit 2 will take place one to two weeks after completing the 4-week LE-mCIMT period and will require about three hours to complete.

Participants will undergo the same functional tests, questionnaires, and biological sampling as in Visit 1(excluding DNA testing for BDNF alleles if it was already done in Visit 1), enabling comparison across time points.

Additional components of the second assessment visit will include a structured introduction to the telerehabilitation program, during which participants will be informed about the digital platform, its functions, and the procedures for recording daily rehabilitation activities. Participants will also receive detailed instructions on using the activity monitor. These instructions explain proper device placement, the required 7-day wear period, and how to handle the device during daily activities.

At the conclusion of the visit, each participant will be provided with an activity monitor to be worn continuously for seven full days, along with a written instruction sheet summarizing the procedures. The device is small, comfortable, and designed not to interfere with daily activities. To facilitate the return of the device, a prepaid, padded return envelope will be provided. Participants will be instructed to place the device in the envelope immediately after completing the monitoring period and to return it to the research team by mail.

For one week following completion of the LE-mCIMT program, participants will wear an activity monitor continuously for seven full days. The device will be positioned on the thigh using an adhesive patch or strap. Throughout the monitoring period, the activity monitor will record detailed information on daily movement patterns, including time spent sitting, standing, and stepping, total step count, and the number of postural transitions. This measurement period will provide objective data on participants' everyday physical activity after the intervention.

Telerehabilitation Program (8 Weeks):

All participants, regardless of group, will receive access to a digital telerehabilitation platform after LE-mCIMT. The program will include a digital diary that allows participants to record their daily rehabilitation-related activities, including walking, physiotherapy sessions, prescribed rehabilitation exercises, gym training, and any other physical activities undertaken during the study period. Through the same platform, participants will also access their personalized rehabilitation plan. The platform will provide home exercise programs prescribed by the physiotherapist, accompanied by written instructions and/or instructional videos to support the correct performance of each exercise.

The content will be adapted to each participant's needs, functional level, and rehabilitation goals.

Post-Telerehabilitation Measurement:

After completing the 8-week telerehabilitation program, an activity monitor will be mailed to the participant, worn for 7 full days and returned in the prepaid padded envelope.

Participants will also complete self-report questionnaires (SIS, HADS, Exercise Self-Efficacy) via the platform.

Data Management and Monitoring:

Data from functional assessments, questionnaires, biological samples, aerobic capacity tests, and activity monitoring will be coded and stored securely. The digital platform will enable the remote collection of questionnaire and activity data. Only authorized research personnel will have access to identifiable information. Adherence to both aerobic exercise sessions and telerehabilitation will be monitored through therapist logs and app usage statistics.

Inclusion Criteria:

• Age between 18 and 70 years.
• History of a first-ever stroke occurring at least 6 months before enrollment.
• Independence in personal activities of daily living (e.g., dressing, undressing, and using the toilet).
• Ability to take a few steps indoors without a walking aid and without supervision; use of an orthosis is permitted.

Exclusion Criteria:

• Unstable cardiovascular disease or exercise-induced epilepsy.
• Insufficient cognitive ability to participate in group-based training, including the capacity to understand, follow, and maintain verbal instructions during exercise tasks.
• Blood pressure >140/90 mmHg at the first visit.

We will follow Swedish laws and regulations and share data upon reasonable request.