TRANSPORT 2: Transcranial Direct Current Stimulation for Post-stroke Motor Recovery

Sponsor

Duke University (Other)

Overall Status

Recruiting

CT.gov ID

NCT03826030

Collaborator

National Institute of Neurological Disorders and Stroke (NINDS) (NIH)

129

Enrollment

Locations

Arms

Anticipated Duration (Months)

9.2

Patients Per Site

0.2

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This research study is to find out if brain stimulation at different dosage level combined with an efficacy-proven rehabilitation therapy can improve arm function. The stimulation technique is called transcranial direct current stimulation (tDCS). The treatment uses direct currents to stimulate specific parts of the brain affected by stroke. The adjunctive rehabilitation therapy is called "modified Constraint-Induced Movement Therapy" (mCIMT). During this therapy the subject will wear a mitt on the hand of the arm that was not affected by a stroke and force to use the weak arm. The study will test 3 different doses of brain stimulation in combination with mCIMT to find out the most promising one.

Condition or Disease	Intervention/Treatment	Phase
Stroke, Ischemic Motor Activity Upper Extremity Paralysis	Device: Sham Device: Low dose tDCS Device: High dose tDCS Behavioral: mCIMT	Phase 2

Study Design

Study Type:

Interventional

Anticipated Enrollment :

129 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Triple (Participant, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

TRANScranial Direct Current Stimulation for POst-stroke Motor Recovery - a Phase II sTudy (TRANSPORT 2)

Actual Study Start Date :

Sep 1, 2019

Anticipated Primary Completion Date :

Nov 1, 2022

Anticipated Study Completion Date :

Jan 1, 2023

Arms and Interventions

Arm	Intervention/Treatment
Sham Comparator: Sham tDCS + mCIMT Sham tDCS (Transcranial direct current stimulation) administers no dose or zero milliampere stimulation through the tDCS device, during Constraint Induced Movement Therapy (mCIMT)	Device: Sham sham group receives no active current stimulation except 15 seconds of current ramp up in the beginning and 15 seconds of current ramp up in the end of the 30-minute session to create a scalp perception to blind the subject. Behavioral: mCIMT All three tDCS groups receive constraint-induced movement therapy as the adjunctive behavioral therapy for 2 hours per session
Active Comparator: 2 mA tDCS + mCIMT 2 mA tDCS (Transcranial direct current stimulation) administers low dose or 2 milliampere stimulation through the tDCS device, during Constraint Induced Movement Therapy (mCIMT)	Device: Low dose tDCS The low dose tDCS group receives direct current stimulation at 2 mA for 30 minutes per session Behavioral: mCIMT All three tDCS groups receive constraint-induced movement therapy as the adjunctive behavioral therapy for 2 hours per session
Active Comparator: 4 mA + mCIMT 4 mA tDCS (Transcranial direct current stimulation) administers high dose or 4 milliampere stimulation through the tDCS device, during Constraint Induced Movement Therapy (mCIMT)	Device: High dose tDCS The high dose tDCS group receives direct current stimulation at 4 mA for 30 minutes per session Behavioral: mCIMT All three tDCS groups receive constraint-induced movement therapy as the adjunctive behavioral therapy for 2 hours per session

Arm

Intervention/Treatment

Sham Comparator: Sham tDCS + mCIMT

Sham tDCS (Transcranial direct current stimulation) administers no dose or zero milliampere stimulation through the tDCS device, during Constraint Induced Movement Therapy (mCIMT)

Device: Sham

sham group receives no active current stimulation except 15 seconds of current ramp up in the beginning and 15 seconds of current ramp up in the end of the 30-minute session to create a scalp perception to blind the subject.

Behavioral: mCIMT

All three tDCS groups receive constraint-induced movement therapy as the adjunctive behavioral therapy for 2 hours per session

Active Comparator: 2 mA tDCS + mCIMT

2 mA tDCS (Transcranial direct current stimulation) administers low dose or 2 milliampere stimulation through the tDCS device, during Constraint Induced Movement Therapy (mCIMT)

Device: Low dose tDCS

The low dose tDCS group receives direct current stimulation at 2 mA for 30 minutes per session

Behavioral: mCIMT

All three tDCS groups receive constraint-induced movement therapy as the adjunctive behavioral therapy for 2 hours per session

Active Comparator: 4 mA + mCIMT

4 mA tDCS (Transcranial direct current stimulation) administers high dose or 4 milliampere stimulation through the tDCS device, during Constraint Induced Movement Therapy (mCIMT)

Device: High dose tDCS

The high dose tDCS group receives direct current stimulation at 4 mA for 30 minutes per session

Behavioral: mCIMT

All three tDCS groups receive constraint-induced movement therapy as the adjunctive behavioral therapy for 2 hours per session

Outcome Measures

Primary Outcome Measures

Mean Change of Motor Impairment as Assessed by Fugl-Meyer Upper-Extremity (FM-UE) scale [Baseline through day 15 (after the intervention) and follow-up at day 45 and 105]
The Fugl-Meyer Upper-Extremity (FM-UE) scale is a measure of motor impairment. FM-UE scale consists of a 33-item assessment which provides a global assessment of UE motor impairment. A rater observes 30 voluntary UE motions and 14 voluntary lower extremity (LE) motions, 6 tendon tap responses, and provides an ordinal rating (2=near normal ability/response, 1=partial ability, 0=unable to perform/no response). FM-UE scale is a proven scale with excellent intra-rater reliability (0.99), inter-rater reliability (0.99), test-retest reliability (0.94 -0.99), and internal consistency (0.97).

Secondary Outcome Measures

Mean Change of Functional Motor Activity as assessed by Wolf Motor Function Test (WMFT) [Baseline through day 15 (after the intervention) and follow-up at day 45 and 105]
The Wolf Motor Function Test (WMFT) is a measure of functional motor activity that quantifies upper extremity (UE) motor ability through timed and functional tasks. The WMFT consists of approximately 17 functional, strength and movement quality tasks. Each task is rated on a 6 point scale. Lower scores on the 6 point scale indicate lower functioning levels (1 = does not attempt with UE being tested, 2= UE being tested does not participate functionally, but an attempt is made to use the UE, 3= Does attempt but requires assistance of the UE not being tested, requires more than 2 attempts to complete, 4= Does attempt but may lack precision, fine coordination or fluidity, 5= Does attempt, movement similar to non-affected side but slightly slower, and 6= Does attempt and movement appears to be normal).
Mean Change of Patient Centered Quality of Life as Assessed by Stroke-Impact-Scale(SIS) hand subscale [Baseline through day 15 (after the intervention) and follow-up at day 45 and 105]
The SIS hand subscale assesses how having a stroke impacts a patient's life. The SIS has 8 subscales which ask questions regarding a patient's physical limitations, memory and thinking, emotions and mood, ability to communicate, daily activities, mobility at home and in the community, use of hand most affected by stroke, and ability to participate in meaningful life activities. Each subscale item is rated on a scale from 5-1 (5= None of the time, 4=a little of the time, 3=Some of the time, 2=Most of the time, 1=All of the time)

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 80 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Each subject must meet all of the following criteria to participate in this study:

18-80 years old; and
First-ever unihemispheric ischemic stroke radiologically verified and occurred within the past 30-180 days; and
10° of active wrist extension, >10° of thumb abduction/extension, and > 10° of extension in at least 2 additional digits; and
Unilateral limb weakness with a Fugl-Meyer Upper Extremity score of ≤ 54 (out of 66) to avoid ceiling effects; and
An absolute difference of FM-UE scores between the two baseline assessments that is ≤ 2 points indicating stable motor impairment; if subject is not stable, then he/she will be invited for a reassessment after 2 weeks (but no more than 3 reassessments); and
Pre-stroke mRS ≤2; and
Signed informed consent by the subject or Legally Authorized Representative (LAR).

Each Subject who meets any of the following criteria will be excluded from the study:

Primary intracerebral hematoma, subarachnoid hemorrhage or bi-hemispheric or bilateral brainstem ischemic strokes;
Medication use at the time of study that may interfere with tDCS, including but not limited to carbamazepine, flunarizine, sulpiride, rivastigmine, dextromethorphan;
Other co-existent neuromuscular disorders (pre- or post-stroke) affecting upper extremity motor function;
Other neurological disorders (pre- or post-stroke) affecting subject's ability to participate in the study;
Moderate to severe cognitive impairment defined as Montreal Cognitive Assessment (MOCA) score < 20/30;
History of medically uncontrolled depression or other neuro-psychiatric disorders despite medications either before or after stroke that may affect subject's ability to participate in the study;
Uncontrolled hypertension despite medical treatment(s) at the time of randomization, defined as SBP≥185 mmHg or DBP≥110 mmHg (patient can be treated, reassessed and randomized later);
Presence of any MRI/tDCS/TMS risk factors including but not limited to: 8a) an electrically, magnetically or mechanically activated metallic or nonmetallic implant including cardiac pacemaker, intracerebral vascular clips or any other electrically sensitive support system; 8b) a non-fixed metallic part in any part of the body, including a previous metallic injury to eye; 8c) pregnancy (effects of MRI, TMS, and tDCS on the fetus are unknown); 8d) history of seizure disorder or post-stroke seizure; 8e) preexisting scalp lesion under the intended electrode placement or a bone defect or hemicraniectomy;
Planning to move from the local area within the next 6 months;
Life expectancy less than 6 months;
Has received Botulinum toxin injection to the affected upper extremity in the past 3 months prior to randomization or expectation that Botulinum will be given to the Upper Extremity prior to the completion of the last follow-up visit;
Concurrent enrollment in another investigational stroke recovery study;
Doesn't speak sufficient English to comply with study procedures;
Expectation that subject cannot comply with study procedures and visits.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Alabama	Birmingham	Alabama	United States	35249
2	University of California Los Angeles	Los Angeles	California	United States	90089
3	MedStar National Rehabilitation Hospital	Washington	District of Columbia	United States	20010
4	Emory University	Atlanta	Georgia	United States	30322
5	University of Kentucky	Lexington	Kentucky	United States	40504
6	Baystate Medical Center	Springfield	Massachusetts	United States	01199
7	Burke Neurological Institute	White Plains	New York	United States	10605
8	Duke University Medical Center	Durham	North Carolina	United States	27710
9	University of Cincinnati	Cincinnati	Ohio	United States	45219
10	Cleveland VA Medical Center	Cleveland	Ohio	United States	44106
11	Moss Rehabilitation Research Institute	Elkins Park	Pennsylvania	United States	19027
12	University of Pittsburgh Medical Center	Pittsburgh	Pennsylvania	United States	15213
13	Medical University of South Carolina	Charleston	South Carolina	United States	29425
14	University of Texas Health Science Center / TIRR Memorial Hermann	Houston	Texas	United States	77030