COBRE_JIpro3: Optimizing Current and Electrode Montage for Transcranial Direct Current Stimulation in Stroke Patients

• Sponsor: Medical University of South Carolina (Other)
• Overall Status: Completed
• CT.gov ID: NCT02763826
• Collaborator: (none)
• Enrollment: 31
• Location: 1
• Arms: 2
• Actual Duration (Months): 52.6
• Patients Per Site Per Month: 0.6

Study Details

Study Description

Brief Summary

The purpose of this study is to determine the optimal transcranial direct current stimulation (tDCS) amplitude and electrode montage that is both safe and efficacious

Condition or Disease	Intervention/Treatment	Phase
Stroke	Device: transcranial direct current stimulation	N/A

Detailed Description

Transcranial direct current stimulation (tDCS) is a non-invasive brain stimulation technique that can modulate cortical excitability of targeted brain regions. Various studies have investigated tDCS use in stroke patients with motor impairments (cumulatively about 200 cases). Although these studies are mostly "proof of concept" with small sample size, they do suggest that tDCS may improve motor function. However these two questions have not been addressed systematically:

1. What is the optimal current for stroke patients?

2. What is the optimal tDCS electrode montage for stimulation?

This proposal lays the scientific foundation for systematic application of tDCS in stroke recovery research by progressively increasing tDCS currents and montages that are both safe and efficacious in population with stroke.

Study Design

• Study Type: Interventional
• Actual Enrollment: 31 participants
• Allocation: Non-Randomized
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Optimizing Current and Electrode Montage for Transcranial Direct Current Stimulation in Stroke Patients
• Actual Study Start Date: Dec 8, 2014
• Actual Primary Completion Date: Apr 26, 2019
• Actual Study Completion Date: Apr 26, 2019

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Determine the Optimal tDCS current We will invesitigate the optimal curent in range of 1 mA to 4 mA. We hypothesize that 4 mA is tolerable, safe and can induce the highest level of cortical excitability in the lesional motor cortex.	Device: transcranial direct current stimulation; brain stimulation using progressively increasing amounts of direct currents and in a variety of electrode montages; Other Names: tdcs
Experimental: Determine the optimal tDCS electrode montage We hypothesize that the bi-hemispheric stimulation with anodal stimulation on the lesional hemisphere and simultaneous cathodal stimulation on the non-lesional hemisphere induces more cortical excitability in the lesional hemisphere than either anodal stimulation on the affected hemisphere or cathodal stimulation on non-lesional hemisphere alone.	Device: transcranial direct current stimulation; brain stimulation using progressively increasing amounts of direct currents and in a variety of electrode montages; Other Names: tdcs

Outcome Measures

Primary Outcome Measures

1. Number of Participants With Major Response [Immediately after intervention on the day of tDCS application]

   Major response is any of the following: Second degree scalp burn at the site of electrode pad; or Seizure; or New lesion(s) on Diffusion Weighted Imaging (DWI) sequence of MRI scan and the lesion(s) not explained by any other cause(s) or decreased Apparent Diffusion Coefficient (ADC) under the electrode stimulating motor cortex area; Discontinuation of subject from the study due to any of above. In a 3+3 design, 3 subjects are recruited for a given tDCS dose level. The trial is stopped if ≥2 of 3 subjects at a given tDCS dose level show major response. If only 1 of 3 subjects shows major response, 3 more subjects are recruited at a given tDCS dose level and a major response in any of them will stop the trial. Otherwise, same procedure is followed for the next tDCS dose level. Maximum tolerable dose will be the tDCS dose at the level before stopping of the trial.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 80 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• 18-80 years old with a first-ever ischemic stroke that occurred at least 6 months ago;

• Finished rehabilitation therapy(including inpatient or outpatient Physical Therapy (PT) / Occupational Therapy (OT) / Speech Therapy (SP)) at least one month ago;

• Unilateral limb weakness with Fugl Meyer-Upper Extremity Scale score less than 56 (out of 66);

• Motor Evoked Potentials (MEP) is inducible on abductor pollicis brevis (APB) muscle on the affected side by TMS.

Exclusion Criteria:

• Primary intracerebral hematoma, or subarachnoid hemorrhage,

• Bihemispheric ischemic strokes;

• History of prior stroke or old infarct demonstrated on the CT or MRI or documented in medical records;

• Other concomitant neurological disorders affecting upper extremity motor function;

• Documented history of dementia before or after stroke;

• Documented history of uncontrolled depression or psychiatric disorder either before or after stroke which could affect their ability to participate in the experiment;

• Uncontrolled hypertension despite treatment, specifically Systolic blood pressure (SBP)/ Diastolic Blood Pressure (DBP) >= 180/100 mmHg at baseline;

• Presence of any MRI/tDCS/TMS risk factors: a) an electrically, magnetically or mechanically activated metal or nonmetal implant including cardiac pacemaker, intracerebral vascular clips or any other electrically sensitive support system; b) non-fixed metal in any part of the body, including a previous metallic injury to eye;

1. pregnancy, since the effect of tDCS on the fetus is unknown; d) history of seizure disorder or post-stroke seizure; e) preexisting scalp lesion, bone defect or hemicraniectomy.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Medical University of South Carolina	Charleston	South Carolina	United States	29425

Sponsors and Collaborators

• Medical University of South Carolina

Investigators

• Principal Investigator: Wuwei Feng, MD, MS, MEDICAL UNIVERSITY OF SOUTH CAROL

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Feb 3, 2017

More Information

Publications

None provided.

• Responsible Party: Medical University of South Carolina
• ClinicalTrials.gov Identifier: NCT02763826
• Other Study ID Numbers: Pro00022248
• First Posted: May 5, 2016
• Last Update Posted: Oct 13, 2021
• Last Verified: Oct 1, 2021

• Individual Participant Data (IPD) Sharing Statement: Undecided
• Plan to Share IPD: Undecided
• Keywords provided by Medical University of South Carolina: Transcranial Direct Current Stimulation; tDCS
• Additional relevant MeSH terms: Stroke

Study Results

Participant Flow

Pre-assignment Detail	Part 1 was a 3+3 dose-escalation study, which allowed up to 6 participants at a given dose escalation step. Part 2 was a montage effect study, which was a cross-over study requiring 18 participants to finish the study (by completing 3 visits). Participants enrolled in Part 1 were allowed to be enrolled in Part 2, but repeat participation in the same part by the same subject was not allowed.

Arm/Group Title	1 mA Bihemispheric tDCS	2 mA Bihemispheric tDCS	2.5 mA Bihemispheric tDCS	3 mA Bihemispheric tDCS	3.5 mA Bihemispheric tDCS	4 mA Bihemispheric tDCS	4 mA Anodal tDCS	4 mA Cathodal tDCS
Arm/Group Description	Subjects will get tDCS at a current of 1 mA with bihemispheric montage	Subjects will get tDCS at a current of 2 mA with bihemispheric montage	Subjects will get tDCS at a current of 2.5 mA with bihemispheric montage	Subjects will get tDCS at a current of 3 mA with bihemispheric montage	Subjects will get tDCS at a current of 3.5 mA with bihemispheric montage	Subjects will get tDCS at a current of 4 mA with bihemispheric montage	Subjects will get tDCS at a current of 4 mA with anodal montage	Subjects will get tDCS at a current of 4 mA with cathodal montage
Period Title: Part 1 Dose Escalation, 1 mA
STARTED	3	0	0	0	0	0	0	0
COMPLETED	3	0	0	0	0	0	0	0
NOT COMPLETED	0	0	0	0	0	0	0	0
Period Title: Part 1 Dose Escalation, 1 mA
STARTED	0	3	0	0	0	0	0	0
COMPLETED	0	3	0	0	0	0	0	0
NOT COMPLETED	0	0	0	0	0	0	0	0
Period Title: Part 1 Dose Escalation, 1 mA
STARTED	0	0	3	0	0	0	0	0
COMPLETED	0	0	3	0	0	0	0	0
NOT COMPLETED	0	0	0	0	0	0	0	0
Period Title: Part 1 Dose Escalation, 1 mA
STARTED	0	0	0	3	0	0	0	0
COMPLETED	0	0	0	3	0	0	0	0
NOT COMPLETED	0	0	0	0	0	0	0	0
Period Title: Part 1 Dose Escalation, 1 mA
STARTED	0	0	0	0	3	0	0	0
COMPLETED	0	0	0	0	3	0	0	0
NOT COMPLETED	0	0	0	0	0	0	0	0
Period Title: Part 1 Dose Escalation, 1 mA
STARTED	0	0	0	0	0	3	0	0
COMPLETED	0	0	0	0	0	3	0	0
NOT COMPLETED	0	0	0	0	0	0	0	0
Period Title: Part 1 Dose Escalation, 1 mA
STARTED	0	0	0	0	0	6	6	7
COMPLETED	0	0	0	0	0	6	6	7
NOT COMPLETED	0	0	0	0	0	0	0	0
Period Title: Part 1 Dose Escalation, 1 mA
STARTED	0	0	0	0	0	6	6	6
COMPLETED	0	0	0	0	0	6	6	6
NOT COMPLETED	0	0	0	0	0	0	0	0
Period Title: Part 1 Dose Escalation, 1 mA
STARTED	0	0	0	0	0	6	6	6
COMPLETED	0	0	0	0	0	6	6	6
NOT COMPLETED	0	0	0	0	0	0	0	0

Baseline Characteristics

Arm/Group Title	1 mA Bihemispheric tDCS	2 mA Bihemispheric tDCS	2.5 mA Bihemispheric tDCS	3 mA Bihemispheric tDCS	3.5 mA Bihemispheric tDCS	4 mA Bihemispheric tDCS	Crossover - 4mA Bihemisphere tDCS and 4 mA Anodal tDCS and 4mA Cathodal tDCS	Total
Arm/Group Description	Participants received 1 mA Bihemispheric tDCS	Participants received 2 mA Bihemispheric tDCS	Participants received 2.5 mA Bihemispheric tDCS	Participants received 3 mA Bihemispheric tDCS	Participants received 3.5 mA Bihemispheric tDCS	Participants received 4 mA Bihemispheric tDCS	Stroke subjects will each receive one of three stimulation montages	Total of all reporting groups
Overall Participants	3	3	3	3	3	3	13	31
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Between 18 and 65 years	2 66.7%	3 100%	3 100%	2 66.7%	3 100%	3 100%	0 0%	16 51.6%
>=65 years	1 33.3%	0 0%	0 0%	1 33.3%	0 0%	0 0%	0 0%	2 6.5%
<=18 years	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Between 18 and 65 years	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	9 69.2%	9 29%
>=65 years	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	4 30.8%	4 12.9%
Sex: Female, Male (Count of Participants)
Female	1 33.3%	0 0%	2 66.7%	2 66.7%	1 33.3%	1 33.3%	0 0%	7 22.6%
Male	2 66.7%	3 100%	1 33.3%	1 33.3%	2 66.7%	2 66.7%	0 0%	11 35.5%
Female	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	6 46.2%	6 19.4%
Male	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	7 53.8%	7 22.6%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Asian	1 33.3%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	1 3.2%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Black or African American	0 0%	1 33.3%	1 33.3%	2 66.7%	2 66.7%	1 33.3%	0 0%	7 22.6%
White	2 66.7%	2 66.7%	2 66.7%	1 33.3%	1 33.3%	2 66.7%	0 0%	10 32.3%
More than one race	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
American Indian or Alaska Native	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Asian	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Black or African American	0 0%	00 0%	0 0%	0 0%	0 0%	0 0%	7 53.8%	7 22.6%
White	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	6 46.2%	6 19.4%
More than one race	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Region of Enrollment (Count of Participants)
Dose Escalation	3 100%	3 100%	3 100%	3 100%	3 100%	3 100%	0 0%	18 58.1%
Crossover Period	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	13 100%	13 41.9%

Outcome Measures

1. Primary Outcome

Title	Number of Participants With Major Response
Description	Major response is any of the following: Second degree scalp burn at the site of electrode pad; or Seizure; or New lesion(s) on Diffusion Weighted Imaging (DWI) sequence of MRI scan and the lesion(s) not explained by any other cause(s) or decreased Apparent Diffusion Coefficient (ADC) under the electrode stimulating motor cortex area; Discontinuation of subject from the study due to any of above. In a 3+3 design, 3 subjects are recruited for a given tDCS dose level. The trial is stopped if ≥2 of 3 subjects at a given tDCS dose level show major response. If only 1 of 3 subjects shows major response, 3 more subjects are recruited at a given tDCS dose level and a major response in any of them will stop the trial. Otherwise, same procedure is followed for the next tDCS dose level. Maximum tolerable dose will be the tDCS dose at the level before stopping of the trial.
Time Frame	Immediately after intervention on the day of tDCS application

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	1 mA Bihemispheric tDCS	2 mA Bihemispheric tDCS	2.5 mA Bihemispheric tDCS	3 mA Bihemispheric tDCS	3.5 mA Bihemispheric tDCS	4 mA Bihemispheric tDCS	4 mA Anodal tDCS	4 mA Cathodal tDCS
Arm/Group Description	Subjects will get tDCS at a current of 1 mA with bihemispheric montage	Subjects will get tDCS at a current of 2 mA with bihemispheric montage	Subjects will get tDCS at a current of 2.5 mA with bihemispheric montage	Subjects will get tDCS at a current of 3 mA with bihemispheric montage	Subjects will get tDCS at a current of 3.5 mA with bihemispheric montage	Subjects will get tDCS at a current of 4 mA with bihemispheric montage	Subjects will get tDCS at a current of 4 mA with anodal montage	Subjects will get tDCS at a current of 4 mA with cathodal montage
Measure Participants	3	3	3	3	3	21	18	19
Count of Participants [Participants]	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%

Adverse Events

Time Frame	4 years, 4 months
Arm/Group Title	1 mA Bihemispheric tDCS		2 mA Bihemispheric tDCS		2.5 mA Bihemispheric tDCS		3 mA Bihemispheric tDCS		3.5 mA Bihemispheric tDCS		4 mA Bihemispheric tDCS		4 mA Anodal tDCS		4 mA Cathodal tDCS
Arm/Group Description	Subjects will receive tDCS at 1 mA with bihemispheric montage		Subjects will receive tDCS at 2 mA with bihemispheric montage		Subjects will receive tDCS at 2.5 mA with bihemispheric montage		Subjects will receive tDCS at 3.0 mA with bihemispheric montage		Subjects will receive tDCS at 3.5 mA with bihemispheric montage		Subjects will receive tDCS at 4 mA with bihemispheric montage		Subjects will receive tDCS at 4 mA with anodal montage		Subjects will receive tDCS at 4 mA with cathodal montage
All Cause Mortality
	1 mA Bihemispheric tDCS		2 mA Bihemispheric tDCS		2.5 mA Bihemispheric tDCS		3 mA Bihemispheric tDCS		3.5 mA Bihemispheric tDCS		4 mA Bihemispheric tDCS		4 mA Anodal tDCS		4 mA Cathodal tDCS
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/3 (0%)		0/3 (0%)		0/3 (0%)		0/3 (0%)		1/3 (33.3%)		0/21 (0%)		0/18 (0%)		0/19 (0%)
Serious Adverse Events
	1 mA Bihemispheric tDCS		2 mA Bihemispheric tDCS		2.5 mA Bihemispheric tDCS		3 mA Bihemispheric tDCS		3.5 mA Bihemispheric tDCS		4 mA Bihemispheric tDCS		4 mA Anodal tDCS		4 mA Cathodal tDCS
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/3 (0%)		0/3 (0%)		0/3 (0%)		0/3 (0%)		0/3 (0%)		0/21 (0%)		0/18 (0%)		0/19 (0%)
Other (Not Including Serious) Adverse Events
	1 mA Bihemispheric tDCS		2 mA Bihemispheric tDCS		2.5 mA Bihemispheric tDCS		3 mA Bihemispheric tDCS		3.5 mA Bihemispheric tDCS		4 mA Bihemispheric tDCS		4 mA Anodal tDCS		4 mA Cathodal tDCS
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/3 (0%)		0/3 (0%)		0/3 (0%)		0/3 (0%)		0/3 (0%)		0/21 (0%)		0/18 (0%)		0/19 (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.