kTMP-Enhanced Motor Rehabilitation for Chronic Stroke Recovery (KULMINATE) Pilot

The goal of this pilot clinical trial is to assess the feasibility and preliminary efficacy of kTMP on upper limb motor recovery in chronic stroke compared to sham. We will conduct a 6-week double-blind, randomized, sham-controlled pilot study to test the beneficial influence of kTMP combined with simple motor tasks on kinematic outcomes such as range of motion of the upper arm, hand and fingers.

After baseline assessments, participants will be randomly allocated to either the kTMP group or the Control group. Participants, experimentalists, and outcome assessors will be blinded to group allocation. kTMP will begin within 1 week following randomization and will be delivered three times a week for 6 weeks. The primary endpoint will be assessed at the end of treatment, with follow-up assessments occurring 1 month, 3 months and 6 months following treatment completion. There is one assessment 4 weeks into the treatment phase to assess if patients continue to improve from 4 to 6 weeks of treatment.

Inclusion criteria

• Adults aged 18-80 years who have a history of an ischemic or hemorrhagic stroke ≥ 12 m prior to enrollment.
• Fugl-Meyer Assessment: Upper Extremity (FMA UE) score 20-50.
• Ability to communicate, understand, and give appropriate consent. Participants can follow two-step commands.
• Motor evoked potentials in a hand muscle when stimulating ipsilesional cortex with suprathreshold single-pulse TMS (MEP positive).

Exclusion criteria

• Participants with moderate or severe cognitive impairment (MoCA < 18).
• Participants with sensory deficits FMA-S < 6/12 (with proprioception < 4/8).
• Participants with severe apraxia (TULIA < 5).
• Language impairment or behavioral disorder that interferes with their ability to adhere to the protocol or to provide informed consent.
• Individuals who have a serious uncontrolled medical condition, including but not limited to severe cardiovascular and cardiopulmonary disease.
• Pregnancy or plans to become pregnant during the study period.
• Botulinum toxin injections of the affected upper extremity within 3 months prior to onset of study.
• Severe spasticity of the affected upper limb (Modified Ashworth ≥ 4).
• Absolute contraindications related to non-invasive brain stimulation, including:

9a) History of seizures in the last 12 months while taking anti-epilepsy medication 9b) Presence of any metal implants in the head (excluding the mouth), such as cortical stimulators and DBS, clips, coils, shunts, stents or skull plates, cochlear implants 9c) Permanent eye liner or head tattoos 9d) Implanted electronics such as pacemakers, defibrillators, intrathecal baclofen pumps or vagus nerve stimulator 9e) History of experiencing a serious adverse event during a previous transcranial magnetic stimulation (TMS) session