Contrastim Stroke Trial

NCT ID: NCT01049802

Last Updated: 2016-12-29

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE1/PHASE2

Total Enrollment

30 participants

Study Classification

INTERVENTIONAL

Study Start Date

2010-01-31

Study Completion Date

2016-09-30

Brief Summary

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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

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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.

Conditions

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Stroke

Keywords

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stroke hemiplegia TMS

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

TRIPLE

Participants Caregivers Outcome Assessors

Study Groups

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Active rTMS

Experimental subjects will receive subthreshold or suprathreshold rTMS to contralesional hemisphere for up to 20 minutes at 1 Hz followed by task oriented arm and hand therapy to affected limb.

Group Type EXPERIMENTAL

Repetititve transcranial magnetic stimulation

Intervention Type DEVICE

1 Hz rTMS to contralesional hemisphere in patients with stroke

Sham rTMS

Subject will receive sham rTMS to contralesional hemisphere for up to 20 minutes followed by task-oriented arm and hand rehabilitation to affected limb

Group Type PLACEBO_COMPARATOR

Repetititve transcranial magnetic stimulation

Intervention Type DEVICE

1 Hz rTMS to contralesional hemisphere in patients with stroke

Interventions

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Repetititve transcranial magnetic stimulation

1 Hz rTMS to contralesional hemisphere in patients with stroke

Intervention Type DEVICE

Eligibility Criteria

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Inclusion Criteria

* ≥ 18 years of age
* An ischemic or hemorrhagic stroke suffered 3-9 months prior to the study
* no other known brain abnormalities by history or by structural MRI
* A one-sided stroke resulting in upper extremity paresis
* A Chedoke Arm and Hand Activity Inventory score of 3-6 for the affected limb

Exclusion Criteria

* Implanted metallic parts of implanted electronic devices, including pacemakers, defibrillators, or implant medication pump
* Pregnant or trying to become pregnant
* History of alcohol abuse, illicit drug use or drug abuse or significant mental illness
* any history of epilepsy
* Any condition that would prevent the subject from giving voluntary informed consent
* An implanted brain stimulator
* Aneurysm clip or other metal in body
* Enrolled or plans to enroll in an interventional trial during this study
* Scalp wounds or infections
* Claustrophobia precluding MRI
* A fixed contraction deformity in the affected limb
* Excessive spasticity as indicated by the Modified Ashworth Spasticity (MAS) Scale \>2/4 in the affected limb
* previous stroke with residual deficits (TIAs not a reason for exclusion)
* premorbid (retrospective) modified Rankin Scale (mRS) score ≥2 of any aetiology
* a concurrent progressive neurologic disorder, acute coronary syndrome, severe heart disease (NYHA Classification \> 3), or other major medical condition
* confirmed or suspected lower-limb fracture preventing mobilization
* patients requiring palliative care
* patients undergoing any other occupational therapy than what is provided in the study
* A recent injection of botulinum toxin to the affected upper limb in the last 3 months, or the need of an injection of botulinum toxin anytime during the study period and follow up
* Ataxia as measured by a score \> 1 on item 7 (limb ataxia) of the NIH stroke scale
* Severe aphasia as measured by a score of \> 2 on item 9 (best language) of the NIH stroke scale
* Severe neglect as measured by a score of 2 on item 11 (extinction and inattention) of the NIH stroke scale
Minimum Eligible Age

18 Years

Maximum Eligible Age

90 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Nexstim Ltd

INDUSTRY

Sponsor Role collaborator

Shirley Ryan AbilityLab

OTHER

Sponsor Role lead

Responsible Party

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Richard Harvey

Medical Director of Stroke Rehabilitation

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Richard L Harvey, MD

Role: PRINCIPAL_INVESTIGATOR

The Rehabilitation Institute of Chicago

Jarmo Laine, MD, PhD, MBA

Role: STUDY_DIRECTOR

Nexstim Ltd

Locations

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The Rehabilitation Institute of Chicago

Chicago, Illinois, United States

Site Status

Countries

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United States

Related Links

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http://www.ric.org

The Rehabilitation Institute of Chicago

Other Identifiers

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NR-001

Identifier Type: -

Identifier Source: org_study_id