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

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

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.

Study Overview

• Status: Recruiting
• Conditions: Stroke, Ischemic; Motor Activity; Upper Extremity Paralysis
• Intervention / Treatment: Device: Sham; Behavioral: mCIMT; Device: Low dose tDCS; Device: High dose tDCS

• Study Type: Interventional
• Enrollment (Estimated): 129
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Wayne Feng, MD; Phone Number: (919) 681-1700; Email: wayne.feng@duke.edu
• Study Contact Backup: Name: Gottfried Schlaug, MD; Email: Gottfried.Schlaug@baystatehealth.org

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States, 35249
      • Active, not recruiting
      • University of Alabama
  • California
    • Los Angeles, California, United States, 90089
      • Completed
      • University of California Los Angeles
  • District of Columbia
    • Washington, District of Columbia, United States, 20010
      • Recruiting
      • MedStar National Rehabilitation Hospital
      • Contact: Margot Giannetti; Phone Number: 202-877-1071; Email: margot.giannetti@medstar.net
      • Principal Investigator: Richard D Zorowitz, MD
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Recruiting
      • Emory University
      • Contact: Susan Murphy; Phone Number: 404-712-1928; Email: smurph7@emory.edu
      • Principal Investigator: Michael R Borich, PhD
  • Kentucky
    • Lexington, Kentucky, United States, 40504
      • Completed
      • University of Kentucky
  • Massachusetts
    • Springfield, Massachusetts, United States, 01199
      • Recruiting
      • Baystate Medical Center
      • Principal Investigator: Gottfried Schlaug, MD
      • Contact: Abraham Madjidov, BS; Phone Number: 413-794-9565; Email: Abraham.Madjidov@baystatehealth.org
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Recruiting
      • Duke University Medical Center
      • Contact: Tato Sokhadze, PhD; Phone Number: 919-684-3801; Email: estate.sokhadze@duke.edu
      • Principal Investigator: Jody Feld, PhD, PT
  • Ohio
    • Cincinnati, Ohio, United States, 45219
      • Recruiting
      • University of Cincinnati
      • Contact: Colin Drury; Phone Number: 314-753-5654; Email: drurycd@ucmail.uc.edu
      • Principal Investigator: Oluwole Awosika, MD
    • Cleveland, Ohio, United States, 44106
      • Recruiting
      • Cleveland VA Medical Center
      • Principal Investigator: Svetlana Pundik, MD
      • Contact: Ahlam Salameh; Phone Number: 330-203-1918; Email: ais20@case.edu
  • Pennsylvania
    • Elkins Park, Pennsylvania, United States, 19027
      • Recruiting
      • Moss Rehabilitation Research Institute
      • Contact: Sapna Kumar; Phone Number: 215-663-6702; Email: KumarSap@einstein.edu
      • Principal Investigator: Dylan Edwards, PT,PhD
      • Principal Investigator: Ning Cao, MD
    • Pittsburgh, Pennsylvania, United States, 15213
      • Recruiting
      • University of Pittsburgh Medical Center
      • Contact: Jason Weimer; Email: weimerjm@upmc.edu
      • Contact: Amy Boos; Email: amy.boos@pitt.edu
      • Principal Investigator: George Wittenberg, MD
  • South Carolina
    • Charleston, South Carolina, United States, 29425
      • Recruiting
      • Medical University of South Carolina
      • Principal Investigator: Chris Gregory, PhD, PT
      • Contact: Valerie Salisbury; Email: eichvr@musc.edu
  • Texas
    • Houston, Texas, United States, 77030
      • Recruiting
      • University of Texas Health Science Center / TIRR Memorial Hermann
      • Contact: Emily Stevens; Phone Number: 713-500-7914; Email: emily.a.stevens@uth.tmc.edu
      • Principal Investigator: Gerard Francisco, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

1. 18-80 years old; and
2. First-ever unihemispheric ischemic stroke radiologically verified and occurred within the past 30-180 days; and
3. >10° of active wrist extension, >10° of thumb abduction/extension, and > 10° of extension in at least 2 additional digits; and
4. Unilateral limb weakness with a Fugl-Meyer Upper Extremity score of ≤ 54 (out of 66) to avoid ceiling effects; and
5. 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 7-14 days (but no more than 3 reassessments); and
6. Pre-stroke mRS ≤2; and
7. 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:

1. Primary intracerebral hematoma, subarachnoid hemorrhage or bi-hemispheric or bilateral brainstem ischemic strokes;
2. Medication use at the time of study that may interfere with tDCS, including but not limited to carbamazepine, flunarizine, sulpiride, rivastigmine, dextromethorphan;
3. Other co-existent neuromuscular disorders (pre- or post-stroke) affecting upper extremity motor function;
4. Other neurological disorders (pre- or post-stroke) affecting subject's ability to participate in the study;
5. Moderate to severe cognitive impairment defined as Montreal Cognitive Assessment (MOCA) score < 18/30;
6. 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;
7. 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);
8. 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;
9. Planning to move from the local area within the next 6 months;
10. Life expectancy less than 6 months;
11. 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;
12. Concurrent enrollment in another investigational stroke recovery study;
13. Doesn't speak sufficient English to comply with study procedures;
14. Expectation that subject cannot comply with study procedures and visits.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

3

Arms and Interventions

Participant Group / 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)	Behavioral: mCIMT; All three tDCS groups receive constraint-induced movement therapy as the adjunctive behavioral therapy for 2 hours per session; Device: Low dose tDCS; The low dose tDCS group receives direct current stimulation at 2 mA for 30 minutes 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)	Behavioral: mCIMT; All three tDCS groups receive constraint-induced movement therapy as the adjunctive behavioral therapy for 2 hours per session; Device: High dose tDCS; The high dose tDCS group receives direct current stimulation at 4 mA for 30 minutes per session

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean Change of Motor Impairment as Assessed by Fugl-Meyer Upper-Extremity (FM-UE) scale	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).	Baseline through day 15 (after the intervention) and follow-up at day 45 and 105

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean Change of Functional Motor Activity as assessed by Wolf Motor Function Test (WMFT)	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).	Baseline through day 15 (after the intervention) and follow-up at day 45 and 105
Mean Change of Patient Centered Quality of Life as Assessed by Stroke-Impact-Scale(SIS) hand subscale	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)	Baseline through day 15 (after the intervention) and follow-up at day 45 and 105

Collaborators and Investigators

• Sponsor: Duke University
• Collaborators: National Institute of Neurological Disorders and Stroke (NINDS)
• Investigators: Principal Investigator: Wayne Feng, MD, Duke University; Principal Investigator: Gottfried Schlaug, MD, PhD, Baystate Health

Study record dates

Study Major Dates

• Study Start (Actual): September 1, 2019
• Primary Completion (Estimated): October 1, 2024
• Study Completion (Estimated): October 1, 2024

Study Registration Dates

• First Submitted: January 30, 2019
• First Submitted That Met QC Criteria: January 30, 2019
• First Posted (Actual): February 1, 2019

Study Record Updates

• Last Update Posted (Estimated): March 6, 2024
• Last Update Submitted That Met QC Criteria: March 5, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: transcranial direct current stimulation; stroke; stroke recovery; brain stimulation
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurologic Manifestations; Stroke; Ischemic Stroke; Paralysis
• Other Study ID Numbers: Pro00103316; 7U01NS102353-02 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: We will follow the National Institute of Health Stroke Trial Network policy and procedure to share IPD. Please refer to https://nihstrokenet.org/ for detailed information.
• IPD Sharing Time Frame: Please refer to https://nihstrokenet.org/ for detailed information in term of time-frame of sharing such data
• IPD Sharing Access Criteria: Please refer to https://nihstrokenet.org/ for detailed information in term of time-frame of sharing such data

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes