Contrastim Stroke Trial
Condition: Stroke
MeSH terms: Stroke
Study type: Interventional
Phase: Phase 1/Phase 2

Summary: 
      This is a prospective randomized controlled feasibility study to determine whether navigation
      guided repetitive transcranial magnetic stimulation (rTMS) to the healthy hemisphere in
      patients with subacute stroke has a beneficial effect when given concurrently with
      task-oriented motor rehabilitation of the arm and hand. Navigation guided rTMS requires a
      structural MRI scan for targeting stimulation and therefore structural MRI will be performed
      on all subjects. In addition the study intends to determine whether measures of motor tract
      integrity (MTI) assessed by navigated brain stimulation (NBS) and MRI diffusion tensor
      imaging can be used to clarify prognosis of motor recovery and to monitor progress with
      rehabilitation. 30 subjects with ischemic or hemorrhagic stroke 3-9 months prior to
      enrollment and with residual upper limb hemiplegia will be randomized to receive either 1 Hz
      rTMS to the contralesional hemisphere for 30 minutes 3 times a week for 6 weeks along with
      rehabilitation therapy or sham rTMS to the contralesional hemisphere for 30 minutes 3 times a
      week for 6 weeks along with rehabilitation therapy. Primary outcome is improvement on the
      Action Research Arm Test, a measure of arm and hand function in people with stroke. Outcomes
      will be measured immediately post treatment, and at 3 months and 6 months post treatment.
    

Detailed description: 
      PRIMARY OBJECTIVES To determine whether NBS guided 1Hz rTMS targeting the motor
      representation areas of hand muscles on the healthy brain hemisphere has a beneficial effect
      on the motor recovery of the corresponding stroke-affected muscles when combined with
      standardized task-oriented motor rehabilitation.

      SECONDARY OBJECTIVES

        1. To determine whether motor evoked potentials (MEPs) can be elicited from paretic and/or
           plegic muscles in patients with stroke using navigated TMS (eXimia NBS) and targeting
           the anatomical cortical areas representing the affected muscles.

        2. To determine the correlation between existing MEPs, other TMS parameters and the
           clinical deficits of limb function.

        3. To determine the prognostic value of MEPs and other TMS parameters in predicting motor
           recovery after stroke

        4. To determine the diagnostic value of MEPs and other TMS parameters in monitoring the
           response to rehabilitation

        5. To assess safety by capturing all Serious Adverse Events during both single pulse and
           rTMS delivery

      STUDY PROCEDURES

      The purpose of the study including risks and benefits will be explained to potential
      participants who will then be asked to sign an informed consent form. Potential participants
      will be screened for inclusion and exclusion criteria

      The study will be performed in 2 parts. In part 1 Nexstim eXimia NBS will be utilized for
      neuronavigation and a third party TMS will be used for delivering the rTMS. In part 2 Nexstim
      eXimia NBS will be utilized together with Nexstim eXimia TMS for delivering the rTMS. Part 2
      will commence once the patients participating in Part 1 have undergone the study visit 22
      (see 5.1 below).

      15 patients will be recruited to part 1 and 15 patients for part 2 (6 additional subjects
      will be recruited assuming a 20% drop out rate)

      In part 1 of the study 10 subjects will be randomized to rTMS treatment and 5 subjects will
      be randomized to sham rTMS. Of the 10 rTMS treatment subjects, 5 will be given stimulation
      protocol A and 5 will be given stimulation protocol B, described below. In part 2, either
      stimulation protocol A or B will be chosen for continue study based on predetermined outcome
      criteria. In part 2, 10 subjects will receive this chosen rTMS treatment and 5 subjects will
      receive sham rTMS.

      The study will consist of 24 study visits with the addition of 4 additional visits as needed
      to complete outcome assessments.

      VISIT SCHEDULE

      The study will be performed over 24 to 28 sessions:

        1. Visit 1(Screening visit): Baseline = 3-9 months after the stroke. The purpose of this
           visit is to obtain informed consent for the study (if not previously obtained) and to
           screen subjects for inclusion and exclusion criteria.

        2. Visit 2: Baseline assessment. The purpose of this visit is to establish the baseline of
           injury, motor status and NBS parameters (Hand motor mapping and motor tract integrity,
           both hemispheres - see appendix A). Subjects will also undergo a structural MRI. The
           subject will then be randomized to either rTMS or to sham treatment. The baseline visit
           may if necessary take place on 2 separate days.

        3. Visits 3-21: During these visits the patient will undergo standardized task-oriented
           motor rehabilitation of the hand. In addition the patient will receive the rTMS therapy
           according to the protocol of the group she/he was randomized into during visit 1. The
           visits will take place during a 6 week period, three visits per week. During each week
           the visits will take place each on a separate day and a maximum of two visits will take
           place on consecutive days. During the first visit of each week (visits 3, 6, 9, 12, 15
           and 18) in addition to the rTMS and task-oriented motor rehabilitation, the patient will
           undergo measurement of NBS parameters (Motor tract integrity, both hemispheres).

        4. Visit 22: End of the task-oriented motor rehabilitation. The purpose of the visit is to
           establish the extent of recovery that has occurred during the rehabilitation. The visit
           will take place 3-5 days after the last rTMS/rehabilitation session and includes
           functional motor testing and evaluation of NBS parameters (Hand motor mapping and motor
           tract integrity, both hemispheres). 1-2 visits may be needed to complete assessment.

      5) Visit 23: 1 month after the end of the rehabilitation therapy. The purpose of the visit is
      to determine whether any changes in motor function or NBS parameters have occurred within 1
      month of ending therapy. The assessment includes functional motor testing and evaluation of
      NBS parameters (Hand motor mapping and motor tract integrity, both hemispheres). 1-2 visits
      may be needed to complete assessment.

      6) Visit 24: 6 months after end of the rehabilitation therapy. The purpose of this visit is
      to determine the long-term rehabilitation success. The assessment includes functional motor
      testing and evaluation of NBS parameters (Hand motor mapping and motor tract integrity, both
      hemispheres. In patients experience a new stroke or TIA during this time, only the data prior
      to the event will be used in the analysis. 1-2 visits may be needed to complete assessment.
    

Intervention name(s): Repetititve transcranial magnetic stimulation
Intervention type(s): Device
Intervention description(s): 1 Hz rTMS to contralesional hemisphere in patients with stroke
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Outcomes Assessor)
Primary purpose: Treatment
Keywords: stroke; hemiplegia; TMS