A Novel Approach for Brain Stimulation in Severe Stroke
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT03868410|
Recruitment Status : Recruiting
First Posted : March 11, 2019
Last Update Posted : August 9, 2021
The long-term goal of this project is to develop upper limb rehabilitation interventions that can be utilized for stroke survivors, specifically survivors with more severe limitations in use of their affected upper limb.
This study will utilize a novel method of non-invasive brain stimulation in conjunction with upper limb training given for 15 visits over a period of 5 weeks.
The study will include the following site visits:
- Eligibility Screening and Informed Consent Visit
- An MRI visit
- Two testing visits in which motor function of the upper limb and neurophysiology will be measured
- Fifteen intervention visits during which patients will receive upper limb training in conjunction with non-invasive brain stimulation
- Repeat testing of motor function of the upper limb and neurophysiology
- Repeat MRI testing
- A follow-up visit completed 3 months after the completion of interventions
|Condition or disease||Intervention/treatment||Phase|
|Stroke||Device: New rTMS Approach Device: Conventional rTMS Approach||Early Phase 1|
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||24 participants|
|Intervention Model:||Parallel Assignment|
|Intervention Model Description:||In a pilot, randomized-controlled, double-blind study, an anticipated 24 patients will be assigned to either receive stimulation to a new brain target- contralesional dorsal premotor cortex (cPMd) located in the non-stroke hemisphere- or the conventional brain target- ipsilesional primary motor cortex (iM1) located in the stroke hemisphere. Stimulation will be delivered in conjunction with rehabilitation for 3 days a week for 5 weeks.|
|Masking:||Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)|
|Masking Description:||Subjects will be told they will receive brain stimulation, but will be given no indication as to which target will be stimulated. Investigators analyzing functional outcome data, neurophysiology data and MRI data will receive coded data that conceals the identity of the subject.|
|Official Title:||A Novel Approach for Brain Stimulation in Severe Stroke|
|Actual Study Start Date :||April 1, 2019|
|Estimated Primary Completion Date :||June 30, 2022|
|Estimated Study Completion Date :||September 30, 2022|
Active Comparator: cPMD rTMS + Training
Device: New rTMS Approach
Participants in this arm will receive rTMS-based facilitation of the contralesional dorsal premotor cortex (cPMd) located in the non-stroke hemisphere before start of each session. High-frequency rTMS (5-Hz) will be delivered using five 1-min trains of 300 pulses each (total 1500 pulses) for a period of 10 minutes. Immediately after the completion of rTMS, participants will undergo upper limb training for a total of one hour. Participants will receive these interventions 3 days a week for 5 weeks, i.e., for a total of 15 sessions.
Other Name: cPMd rTMS + Training
Active Comparator: iM1 rTMS + Training
Device: Conventional rTMS Approach
Participants in this arm will receive rTMS-based facilitation of the ipsilesional primary motor cortex (iM1) before the start of each session. iM1 will be facilitated using a widely-used approach of stimulation delivered to inhibit the contralesional motor cortices located in the non-stroke hemisphere. Low-frequency rTMS (1-Hz) can inhibit the excitability of targeted regions. Therefore, this low-frequency approach will be delivered to suppress the excitability of the non-stroke hemisphere. A total of 1500 pulses will be given for 25 minutes. Immediately after the completion of rTMS, participants will undergo upper limb training for a total of one hour. Participants will receive these interventions 3 days a week for 5 weeks, i.e., for a total of 15 sessions.
Other Name: iM1 rTMS + Training
- Change in Upper Extremity Fugyl-Meyer Score (UEFM) [ Time Frame: through study completion, on average 6 weeks ]Impairment will be measured using UEFM, one of the most widely used assessments in stroke. UEFM will serve as our primary outcome because it is sensitive to discerning the effects of rTMS/rehabilitation, and has excellent reliability (ICC= 0.97), consistency (Cronbach's α= 0.84) and validity. UEFM has a score ranging from 0-66 (0 meaning there is no movement of the paretic arm, and 66 meaning there is no functional limitation of the paretic arm.)
- Change in Inter-hemispheric Inhibition (IHI) [ Time Frame: through study completion, on average 6 weeks ]Inter-hemispheric connectivity will be characterized using IHI collected with TMS.
- Change in Wolf Motor Function Test (WMFT) [ Time Frame: through study completion, on average 6 weeks ]Functional ability to use the paretic upper limb in a variety of tasks will be assessed using WMFT. Time to complete each task will be noted and converted to rate (60/Performance Time (sec)), optimized for measurement in moderately/severely-impaired patients. Grip strength will also be recorded with WMFT.
- Change in Reaching Response Time [ Time Frame: through study completion, on average 6 weeks ]Proximal motor control will be assessed using the reaching response-time task, which, as the name suggests, measures the time required to reach forward and push a cued button. This task is used to characterize motor control in moderately/severely-impaired patients who typically lack adequate distal movements.
- Change in Stroke Impact Scale (SIS-16) [ Time Frame: through study completion, on average 6 weeks ]Patient's perceived disability related to physical function will be indexed using the Stroke Impact Scale (SIS-16) which a subjective questionnaire asked to the subject pertaining of 16 questions. Each question is rated 1-5 and then the scores are totaled. Total scores can range from 16-80 (16 means that none of the functional tasks asked can be performed, a score of 80 means the subject has no issues at all performing any of the tasks asked).
- Change Resting State Functional Magnetic Resonance Imaging(rsfMRI) [ Time Frame: through study completion, on average 6 weeks ]Functional connectivity will complement IHI measurement as a secondary outcome because while IHI records neurophysiologic interactions between a contralesional and a weak ipsilesional region, functional connectivity defines "global" interactions across multiple regions.
- Change in ipsilateral MEPs (motor evoked potentials) [ Time Frame: through study completion, on average 6 weeks ]Output of uncrossed pathways will be studied as ipsilateral MEPs elicited in the paretic-muscle with TMS.
- DTI [ Time Frame: Baseline ]DTI enables the investigation of structural integrity and orientation of pathways in vivo through the estimation of magnitude and directionality of water diffusion. DTI metrics can help quantitate damage even when patients show no response to TMS due to extensive damage (MEP-). Ipsilesional and contralesional corticospinal tracts will be reconstructed using probabilistic tractography. FA, a unit-less measure of white matter integrity, will be calculated.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03868410
|Contact: Kyle J. O'Laughlin, MSemail@example.com|
|Contact: Ela Plow, PhDfirstname.lastname@example.org|
|United States, Ohio|
|Lerner Research Institute; Cleveland Clinic Foundation||Recruiting|
|Cleveland, Ohio, United States, 44195|
|Contact: Morgan Widina, MS 866-449-1394 email@example.com|
|Contact: Ela Plow, PhD 216-445-4589 firstname.lastname@example.org|
|Principal Investigator: Ela Plow, PhD|
|Principal Investigator:||Ela Plow, PhD||Lerner Research Institute; Cleveland Clinic Foundation|