Stroke
Conditions
Keywords
Transcranial Direct Current Stimulation, tDCS
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
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.
Interventions
DEVICEtranscranial direct current stimulation
brain stimulation using progressively increasing amounts of direct currents and in a variety of electrode montages
Sponsors
Medical University of South Carolina
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
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; c) 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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. |
Countries
United States
Participant flow
Pre-assignment details
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.
Participants by arm
| Arm | Count |
|---|---|
| 1 mA Bihemispheric tDCS Participants received 1 mA Bihemispheric tDCS | 3 |
| 2 mA Bihemispheric tDCS Participants received 2 mA Bihemispheric tDCS | 3 |
| 2.5 mA Bihemispheric tDCS Participants received 2.5 mA Bihemispheric tDCS | 3 |
| 3 mA Bihemispheric tDCS Participants received 3 mA Bihemispheric tDCS | 3 |
| 3.5 mA Bihemispheric tDCS Participants received 3.5 mA Bihemispheric tDCS | 3 |
| 4 mA Bihemispheric tDCS Participants received 4 mA Bihemispheric tDCS | 3 |
| Crossover - 4mA Bihemisphere tDCS and 4 mA Anodal tDCS and 4mA Cathodal tDCS Stroke subjects will each receive one of three stimulation montages | 13 |
| Total | 31 |
Baseline characteristics
| Characteristic | 1 mA Bihemispheric tDCS | Total | Crossover - 4mA Bihemisphere tDCS and 4 mA Anodal tDCS and 4mA Cathodal tDCS | 4 mA Bihemispheric tDCS | 3.5 mA Bihemispheric tDCS | 3 mA Bihemispheric tDCS | 2.5 mA Bihemispheric tDCS | 2 mA Bihemispheric tDCS |
|---|---|---|---|---|---|---|---|---|
| Age, Categorical Crossover <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Crossover >=65 years | 0 Participants | 4 Participants | 4 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Crossover Between 18 and 65 years | 0 Participants | 9 Participants | 9 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Dose Escalation <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Dose Escalation >=65 years | 1 Participants | 2 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants |
| Age, Categorical Dose Escalation Between 18 and 65 years | 2 Participants | 16 Participants | 0 Participants | 3 Participants | 3 Participants | 2 Participants | 3 Participants | 3 Participants |
| Race (NIH/OMB) Crossover American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Crossover Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Crossover Black or African American | 0 Participants | 7 Participants | 7 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 00 Participants |
| Race (NIH/OMB) Crossover More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Crossover Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Crossover Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Crossover White | 0 Participants | 6 Participants | 6 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Dose Escalation American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Dose Escalation Asian | 1 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Dose Escalation Black or African American | 0 Participants | 7 Participants | 0 Participants | 1 Participants | 2 Participants | 2 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Dose Escalation More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Dose Escalation Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Dose Escalation Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Dose Escalation White | 2 Participants | 10 Participants | 0 Participants | 2 Participants | 1 Participants | 1 Participants | 2 Participants | 2 Participants |
| Region of Enrollment United States Crossover Period | 0 Participants | 13 Participants | 13 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Region of Enrollment United States Dose Escalation | 3 Participants | 18 Participants | 0 Participants | 3 Participants | 3 Participants | 3 Participants | 3 Participants | 3 Participants |
| Sex: Female, Male Crossover Female | 0 Participants | 6 Participants | 6 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Crossover Male | 0 Participants | 7 Participants | 7 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Dose Escalation Female | 1 Participants | 7 Participants | 0 Participants | 1 Participants | 1 Participants | 2 Participants | 2 Participants | 0 Participants |
| Sex: Female, Male Dose Escalation Male | 2 Participants | 11 Participants | 0 Participants | 2 Participants | 2 Participants | 1 Participants | 1 Participants | 3 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk |
|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 3 | 0 / 3 | 0 / 3 | 0 / 3 | 1 / 3 | 0 / 21 | 0 / 18 | 0 / 19 |
| other Total, other adverse events | 0 / 3 | 0 / 3 | 0 / 3 | 0 / 3 | 0 / 3 | 0 / 21 | 0 / 18 | 0 / 19 |
| serious Total, serious adverse events | 0 / 3 | 0 / 3 | 0 / 3 | 0 / 3 | 0 / 3 | 0 / 21 | 0 / 18 | 0 / 19 |
Outcome results
Primary
Number of Participants With Major Response
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
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| 1 mA Bihemispheric tDCS | Number of Participants With Major Response | 0 Participants |
| 2 mA Bihemispheric tDCS | Number of Participants With Major Response | 0 Participants |
| 2.5 mA Bihemispheric tDCS | Number of Participants With Major Response | 0 Participants |
| 3 mA Bihemispheric tDCS | Number of Participants With Major Response | 0 Participants |
| 3.5 mA Bihemispheric tDCS | Number of Participants With Major Response | 0 Participants |
| 4 mA Bihemispheric tDCS | Number of Participants With Major Response | 0 Participants |
| 4 mA Anodal tDCS | Number of Participants With Major Response | 0 Participants |
| 4 mA Cathodal tDCS | Number of Participants With Major Response | 0 Participants |