Can rTMS Enhance Somatosensory Recovery After Stroke?

• Sponsor: VA Office of Research and Development (U.S. Fed)
• Overall Status: Completed
• CT.gov ID: NCT02811913
• Collaborator: (none)
• Enrollment: 20
• Location: 1
• Arms: 3
• Actual Duration (Months): 119.6
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Stroke	Other: repetitive transcranial magnetic stimulation (rTMS); Other: peripheral sensory stimulation	N/A

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 Design

• Study Type: Interventional
• Actual Enrollment: 20 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Double (Participant, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Can rTMS Enhance Somatosensory Recovery After Stroke?
• Actual Study Start Date: Apr 12, 2012
• Actual Primary Completion Date: Jun 1, 2019
• Actual Study Completion Date: Apr 1, 2022

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

1. Change From Baseline in Two-point Discrimination [up to 1 hour after intervention]

   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.

2. Change From Baseline in N20 Somatosensory Evoked Potential(SSEP) Peak Latency [up to 1 hour after intervention]

   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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Louis Stokes VA Medical Center, Cleveland, OH	Cleveland	Ohio	United States	44106

Sponsors and Collaborators

• VA Office of Research and Development

Investigators

• Principal Investigator: Svetlana Pundik, MD, Louis Stokes VA Medical Center, Cleveland, OH

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Feb 12, 2019

More Information

Publications

None provided.

• Responsible Party: VA Office of Research and Development
• ClinicalTrials.gov Identifier: NCT02811913
• Other Study ID Numbers: N1767-P; 12025-H13; NCT04535232
• First Posted: Jun 23, 2016
• Last Update Posted: Apr 29, 2022
• Last Verified: Apr 1, 2022

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• 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
• Keywords provided by VA Office of Research and Development: sensory impairment; sensory deficit; upper limb; transcranial magnetic stimulation; brain stimulation; rehabilitation
• Additional relevant MeSH terms: Stroke

Study Results

Participant Flow

Arm/Group Title	Stroke Cohort
Arm/Group Description	Each subject is provided with three different brain stimulation interventions in a single arm, single session crossover design study 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 peripheral sensory stimulation: peripheral sensory electrical stimulation and vibration of the stroke-affected hand administered concurrently with each rTMS
Period Title: Overall Study
STARTED	20
COMPLETED	16
NOT COMPLETED	4

Baseline Characteristics

Arm/Group Title	Stroke Cohort
Arm/Group Description	Each subject is provided with three different brain stimulation interventions in a single arm, single session crossover design study 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 peripheral sensory stimulation: peripheral sensory electrical stimulation and vibration of the stroke-affected hand administered concurrently with each rTMS
Overall Participants	16
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	59 (8.1)
Sex: Female, Male (Count of Participants)
Female	2 12.5%
Male	14 87.5%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	0 0%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	10 62.5%
White	6 37.5%
More than one race	0 0%
Unknown or Not Reported	0 0%
two point discrimination (mm) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [mm]	12.5 (5.0)

Outcome Measures

1. Primary Outcome

Title	Change From Baseline in Two-point Discrimination
Description	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.
Time Frame	up to 1 hour after intervention

Outcome Measure Data

Analysis Population Description

stroke cohort

Arm/Group Title	High Frequency rTMS	Low Frequency rTMS	Sham rTMS
Arm/Group Description	Each subject is provided with three different brain stimulation interventions in a single arm, single session crossover design study For these sessions, participants received 5Hz rTMS targeting contralesional sensory cortex and peripheral sensory stimulation: peripheral sensory electrical stimulation and vibration of the stroke-affected hand administered concurrently with each rTMS	Each subject is provided with three different brain stimulation interventions in a single arm, single session crossover design study For these sessions, participants received 1Hz rTMS targeting contralesional sensory cortex and peripheral sensory stimulation: peripheral sensory electrical stimulation and vibration of the stroke-affected hand administered concurrently with each rTMS	Each subject is provided with three different brain stimulation interventions in a single arm, single session crossover design study For these sessions, participants received sham Hz rTMS targeting contralesional sensory cortex and peripheral sensory stimulation: peripheral sensory electrical stimulation and vibration of the stroke-affected hand administered concurrently with each rTMS
Measure Participants	16	16	16
Immediately post-intervention	-0.7 (2.7)	-0.5 (1.8)	-0.1 (1.3)
One hour post-intervention	-1.7 (3.5)	-0.3 (1.2)	0.1 (2.1)

2. Primary Outcome

Title	Change From Baseline in N20 Somatosensory Evoked Potential(SSEP) Peak Latency
Description	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.
Time Frame	up to 1 hour after intervention

Outcome Measure Data

Analysis Population Description

stroke cohort

Arm/Group Title	High Frequency rTMS	Low Frequency rTMS	Sham rTMS
Arm/Group Description	Each subject is provided with three different brain stimulation interventions in a single arm, single session crossover design study For these sessions, participants received 5Hz rTMS targeting contralesional sensory cortex and peripheral sensory stimulation: peripheral sensory electrical stimulation and vibration of the stroke-affected hand administered concurrently with each rTMS	Each subject is provided with three different brain stimulation interventions in a single arm, single session crossover design study For these sessions, participants received 1Hz rTMS targeting contralesional sensory cortex and peripheral sensory stimulation: peripheral sensory electrical stimulation and vibration of the stroke-affected hand administered concurrently with each rTMS	Each subject is provided with three different brain stimulation interventions in a single arm, single session crossover design study For these sessions, participants received sham rTMS targeting contralesional sensory cortex and peripheral sensory stimulation: peripheral sensory electrical stimulation and vibration of the stroke-affected hand administered concurrently with each rTMS
Measure Participants	16	16	16
Immediately post-intervention	-1.1 (2.3)	0.1 (2.2)	0.7 (3.0)
One hour post-intervention	0.1 (2.0)	-1.8 (5.8)	1.2 (2.5)

Adverse Events

Time Frame	1 week
Arm/Group Title	High Frequency rTMS		Low Frequency rTMS		Sham rTMS
Arm/Group Description	Each subject is provided with three different brain stimulation interventions in a single arm, single session crossover design study For these sessions, participants received 5Hz rTMS targeting contralesional sensory cortex and peripheral sensory stimulation: peripheral sensory electrical stimulation and vibration of the stroke-affected hand administered concurrently with each rTMS		Each subject is provided with three different brain stimulation interventions in a single arm, single session crossover design study For these sessions, participants received 1Hz rTMS targeting contralesional sensory cortex and peripheral sensory stimulation: peripheral sensory electrical stimulation and vibration of the stroke-affected hand administered concurrently with each rTMS		Each subject is provided with three different brain stimulation interventions in a single arm, single session crossover design study For these sessions, participants received sham rTMS targeting contralesional sensory cortex and peripheral sensory stimulation: peripheral sensory electrical stimulation and vibration of the stroke-affected hand administered concurrently with each rTMS
All Cause Mortality
	High Frequency rTMS		Low Frequency rTMS		Sham rTMS
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/16 (0%)		0/16 (0%)		0/16 (0%)
Serious Adverse Events
	High Frequency rTMS		Low Frequency rTMS		Sham rTMS
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/16 (0%)		0/16 (0%)		0/16 (0%)
Other (Not Including Serious) Adverse Events
	High Frequency rTMS		Low Frequency rTMS		Sham rTMS
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/16 (0%)		0/16 (0%)		0/16 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.