Can rTMS Enhance Somatosensory Recovery After Stroke?

Stroke affects over 795,000 Americans every year and has an enormous impact on the well-being of American Veterans with 6,000 new stroke admissions every year. Many of these stroke survivors are living with disabilities that limit their everyday function. One of the major consequences of stroke is loss of sensation which manifests as inability to perceive touch, temperature, pain or limb movement. Lack of sensation hinders full functional recovery. Current treatments for sensory loss produce only limited improvements and do not achieve full recovery. Therefore, it is critical to develop new therapies to re-train sensory function. The investigators propose to evaluate a novel non-invasive brain stimulation treatment called repetitive Transcranial Magnetic Stimulation (rTMS). The effects of this technique on motor deficits following stroke have been studied, however rTMS for the treatment of sensory loss has not been examined to date. The investigators' study will examine for the first time if rTMS of a sensory brain region can improve sensory function in chronic stroke survivors.

Study Overview

• Status: Completed
• Conditions: Stroke
• Intervention / Treatment: Other: repetitive transcranial magnetic stimulation (rTMS); Other: peripheral sensory stimulation

Detailed Description

Sensory deficits are present in the majority of stroke survivors. Inability to feel movement, touch or pain impairs the investigators' ability to interact with environment and diminished the quality of life. These sensory deficits significantly impair functional activity and slow down recovery during rehabilitation. Currently available sensory rehabilitation techniques can only partially restore sensory function. The main objective of this study is to test a novel approach to improve sensory function after stroke using non-invasive brain stimulation. This pilot study will measure an immediate effect of different repetitive Transcranial Magnetic Stimulation (rTMS) paradigms in a crossover single session design. The effect of intervention is measured with clinical measures of sensory and motor function and with neurophysiological assessment of sensory pathways. If the concept is demonstrated in this pilot study, then following the lead of other investigations of this type, this pilot will provide the foundation to test the efficacy of a long-term multi-session intervention of combined rTMS and peripherally directed therapy.

• Study Type: Interventional
• Enrollment (Actual): 20
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Ohio
    • Cleveland, Ohio, United States, 44106
      • Louis Stokes VA Medical Center, Cleveland, OH

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Medically stable at least 6 months after first ever stroke.
• Sufficient endurance to participate in the study.
• Cognition sufficiently intact to give valid informed consent to participate.
• Age > 18years.
• Ability to follow 2 stage commands.
• Impaired but not absent ability to feel touch, vibration and movement of the affected arm.

Exclusion Criteria:

• Acute or progressive cardiac, renal, respiratory, neurological disorders or malignancy.
• Any psychiatric diagnosis or active psychological condition.
• History of substance abuse within the last 6 months
• More than one ischemic stroke or stroke affecting both sides.
• Claustrophobia, or inability to operate the MRI patient call button.
• Pregnancy or pregnancy planning during the study period.
• Lower motor neuron damage or radiculopathy
• Contraindications for rTMS according to the TMS-use guidelines (Rossi et al 2009).
• Inability to understand English.
• Significant neglect for those with left-sided deficits.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: High frequency rTMS; Each subject is provided with three different brain stimulation interventions in a single arm, single session crossover design study. One of the sessions was 5 Hz rTMS	Other: repetitive transcranial magnetic stimulation (rTMS); 3 types of interventions on different sessions; session 1 - High frequency rTMS targeting contralesional sensory cortex; session 2 - Low frequency rTMS; session 3 - sham rTMS; Other: peripheral sensory stimulation; peripheral sensory electrical stimulation and vibration of the stroke-affected hand administered concurrently with each rTMS
Other: Low frequency rTMS; Each subject is provided with three different brain stimulation interventions in a single arm, single session crossover design study. One of the sessions was 1 Hz rTMS	Other: repetitive transcranial magnetic stimulation (rTMS); 3 types of interventions on different sessions; session 1 - High frequency rTMS targeting contralesional sensory cortex; session 2 - Low frequency rTMS; session 3 - sham rTMS; Other: peripheral sensory stimulation; peripheral sensory electrical stimulation and vibration of the stroke-affected hand administered concurrently with each rTMS
Other: Sham rTMS; Each subject is provided with three different brain stimulation interventions in a single arm, single session crossover design study. One of the sessions was sham rTMS	Other: repetitive transcranial magnetic stimulation (rTMS); 3 types of interventions on different sessions; session 1 - High frequency rTMS targeting contralesional sensory cortex; session 2 - Low frequency rTMS; session 3 - sham rTMS; Other: peripheral sensory stimulation; peripheral sensory electrical stimulation and vibration of the stroke-affected hand administered concurrently with each rTMS

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Two-point Discrimination	Baseline measure is collected immediately before the intervention. There are two data collections following each intervention, one datacollection is immediately after the intervention and the second one is at 1 hour after intervention. Two-point discrimination was measured with Disk-Criminator disks (Baltimore, MD) by determining the subjects' ability to perceive two points on the disk as two separate points rather than as a single point. The distances between the two points ranged between 2 and 15 mm. One and two sensory points were presented in a pseudo-random order to subjects' 4th digit volar fingertip surface. A threshold is determined when seventy percent accuracy is exhibited for identifying the difference between single versus double point stimulation.	up to 1 hour after intervention
Change From Baseline in N20 Somatosensory Evoked Potential(SSEP) Peak Latency	Baseline measure is collected immediately before the intervention. Following each intervention, data is collected immediately after each intervention and at 1 hour after intervention. SEPs were recorded with a Cadwell Sierra Wave (Cadwell, Kennewick, WA) (LSCDVAMC) or with Powerlab 4/25T (AD Instruments Inc. Colorado Springs, CO) and a Grass Stimulator (Natus Neurology, Middleton, WI) (CC)44. The recording electrodes (1 cm diameter, gold cup electrodes filled with conductive paste) were placed 2 cm posterior to C3 & C4 (10-20 international system of EEG electrode placement) and the reference electrode at Fz (Figure 1). Stimulus was applied to the median nerve at the wrist. Ground electrodes were placed at the lateral epicondyle of the stimulated arm. The evoked response from 500 stimuli were recorded and averaged for a single trial. Three SEP trials were recorded then analyzed. Latencies (in milliseconds) were determined for N20.	up to 1 hour after intervention

Collaborators and Investigators

• Sponsor: VA Office of Research and Development

Publications and helpful links

General Publications

• Pundik S, Skelly M, McCabe J, Akbari H, Tatsuoka C, Plow EB. Does rTMS Targeting Contralesional S1 Enhance Upper Limb Somatosensory Function in Chronic Stroke? A Proof-of-Principle Study. Neurorehabil Neural Repair. 2021 Mar;35(3):233-246. doi: 10.1177/1545968321989338. Epub 2021 Jan 29.

Study record dates

Study Major Dates

• Study Start (Actual): April 12, 2012
• Primary Completion (Actual): June 1, 2019
• Study Completion (Actual): April 1, 2022

Study Registration Dates

• First Submitted: June 21, 2016
• First Submitted That Met QC Criteria: June 21, 2016
• First Posted (Estimate): June 23, 2016

Study Record Updates

• Last Update Posted (Actual): April 29, 2022
• Last Update Submitted That Met QC Criteria: April 4, 2022
• Last Verified: April 1, 2022

More Information

Terms related to this study

• Keywords: rehabilitation; upper limb; brain stimulation; transcranial magnetic stimulation; sensory deficit; sensory impairment
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Stroke
• Other Study ID Numbers: N1767-P; 12025-H13 (Other Identifier: Louis Stokes Cleveland VA Medical Center IRB)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No