tdcs: Use of Transcranial Direct Current Stimulation (tDCS) Coupled With Constraint Induced Movement Therapy in Stroke Patient

• Sponsor: Spaulding Rehabilitation Hospital (Other)
• Overall Status: Completed
• CT.gov ID: NCT01143649
• Collaborator: (none)
• Enrollment: 44
• Location: 1
• Arms: 6
• Actual Duration (Months): 69
• Patients Per Site Per Month: 0.6

Study Details

Study Description

Brief Summary

The purpose of this study is to determine whether noninvasive brain stimulation associated with motor learning offers an additional benefit than motor learning alone in patients with stroke.

The investigators hypothesis is that active transcranial direct current stimulation (tDCS) combined with constraint induced movement therapy (CIMT) will induce a greater motor function improvement as compared with sham tDCS combined with CIMT.

Condition or Disease	Intervention/Treatment	Phase
Stroke; Healthy	Device: transcranial direct current stimulation (tDCS); Procedure: constraint induced movement therapy (CIMT); Device: transcranial alternating current stimulation (tACS)	N/A

Detailed Description

In this 3 experiments study we will evaluate the effect of tDCS and constraint induced movement therapy (CIMT) in stroke patients (exp 1) as well as in healthy subjects (control population - exp 2). Finally we will investigate the effect of tACS - transcranial alternating current stimulation - as an alternative to tDCS, on motor function in healthy subjects (exp 3). The two experiments on tDCS are parallels (exp 1 & 2), while the experiment on tACS uses a crossover design (exp 3).

For stroke patients (Exp1), our primary outcome measure is a clinical scale (Jebsen-Taylor Hand Function Test), while for healthy subjects (Exp 2) we investigate the effect of tDCS and CIMIT on cortico-spinal excitability using TMS - transcranial magnetic stimulation. Finally, for the third experiment using tACS, our primary outcome is cortical oscillation, as measured by EEG - electroencephalogram.

Study Design

• Study Type: Interventional
• Actual Enrollment: 44 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Effects of Transcranial DC Stimulation Coupled With Constraint Induced Movement Therapy on Motor Function in Stroke Patients
• Actual Study Start Date: Apr 1, 2010
• Actual Primary Completion Date: Apr 1, 2011
• Actual Study Completion Date: Jan 1, 2016

Arms and Interventions

Arm	Intervention/Treatment
Experimental: active tDCS + CIMT - stroke patients Participants will receive 5 sessions of tDCS over the primary motor cortex (M1). We will use the following stimulation parameters: intensity of 1mA and for the first 40 minutes of constraint induced movement therapy (CIMT - 10 consecutive sessions Monday- Friday).	Device: transcranial direct current stimulation (tDCS); Subjects will be stimulated at 1 mA for 40 minutes.; Procedure: constraint induced movement therapy (CIMT)
Experimental: active tDCS + CIMT - Healthy Participants will receive one session of tDCS over the primary motor cortex (M1). We will use the following stimulation parameters: intensity of 1mA and for the first 40 minutes of constraint induced movement therapy (CIMT)	Device: transcranial direct current stimulation (tDCS); Subjects will be stimulated at 1 mA for 40 minutes.; Procedure: constraint induced movement therapy (CIMT)
Experimental: tACS - Healthy Subjects The investigators will have 40 healthy subjects who will undergo one session of treatment with active tACS (in which the order in which they receive either sham or active transcranial alternating current stimulation (tACS) stimulation will be randomized).	Device: transcranial alternating current stimulation (tACS); Subjects will be stimulated at 15Hz for 20 minutes.
Sham Comparator: sham tDCS + CIMT - stroke patients Participants will receive 5 sessions of tDCS over the primary motor cortex (M1). We will use the following stimulation parameters: intensity of 1mA and for the first 40 minutes of constraint induced movement therapy (CIMT - 10 consecutive sessions Monday- Friday). For the sham session, tDCS is turned off after 30seconds.	Device: transcranial direct current stimulation (tDCS); Subjects will be stimulated at 1 mA for 40 minutes.; Procedure: constraint induced movement therapy (CIMT)
Sham Comparator: sham tDCS + CIMT - Healthy Participants will receive one session of tDCS over the primary motor cortex (M1). We will use the following stimulation parameters: intensity of 1mA and for the first 40 minutes of constraint induced movement therapy (CIMT). The sham stimulation consists of 30 seconds of stimulation at the beginning of the 40 min of treatment.	Device: transcranial direct current stimulation (tDCS); Subjects will be stimulated at 1 mA for 40 minutes.; Procedure: constraint induced movement therapy (CIMT)
Sham Comparator: sham tACS - Healthy Subjects The investigators will have 40 healthy subjects who will undergo one day of treatment with sham tACS. All participants received active and sham stimulation in a randomized order.	Device: transcranial alternating current stimulation (tACS); Subjects will be stimulated at 15Hz for 20 minutes.

Outcome Measures

Primary Outcome Measures

1. Jebsen Taylor Hand Function Test [2 weeks]

   Jebsen Taylor Hand Function Test: measures hand function in real-life activities, by evaluating the time required to perform 7 different tasks. We used the non-cronstrained hand for the assessments. The sum of the different tasks was used for the analysis.

2. Cortical Excitability [1 hour]

   Motor evoked potential (MEP) Using Transcranial Magnetic Stimulation (TMS), MEP were recorded before and after tDCS (both active and sham). The percentage of change in MEP (post versus pre intervention) between the two groups (active and sham) were used for the comparison.

3. Cortical Oscillations - EEG [15 minutes]

   Recording took place in a dim-lighted room set up with acoustic and electric isolation. EEG was acquired from 64-channels HydroCel Geodesic Sensor Net (Electrical Geodesic Inc., Eugene, OH) and recorded using Net Station running on a MacIntosh G4 computer. Alpha power were used as the main outcome measure. The difference values (e.g., post minus pre tACS) were used for the analysis. The alpha frequency is a brain oscillation that takes place especially when subjects are in a relaxed state, especially eyes closed. In the motor cortex, a decrease in alpha power has been seen during motor performance. Therefore, it could be speculated that a decrease in power in this study would indicate more engagement in motor cortex during the motor performance.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 90 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

All subjects must be between the ages of 18-90 and must not be pregnant.

Additional Entry criteria for Stroke subject enrollment:

1. First-time clinical ischemic or hemorrhagic cerebrovascular accident - evidenced by a radiological (or physician's) report;

2. Weakness, defined as score of less than 55 (out of 66) on arm motor Fugl-Meyer (FM) scale

3. Stroke onset >6 months prior to study enrollment.

Exclusion Criteria:

1. Significant pre-stroke disability;

2. Major depression, as defined by Hamilton Depression (HAM-D) scale grater then or equal 17 if needed (history of depression before the stroke);

3. Any substantial decrease in alertness, language reception, or attention that might interfere with understanding instructions for motor testing;

4. Excessive pain in any joint of the paretic extremity (not applicable to severe stroke subjects);

5. Contraindications to single pulse Transcranial Magnetic Stimulation (TMS) (TMS will be used to measure cortical excitability) such as metal head implants

• history of seizures

• unexplained loss of consciousness

• metal in the head

• frequent or severe headaches or neck pain

• implanted brain medical devices.

1. Contraindications to tDCS

• metal in the head

• implanted brain medical devices

1. Advanced liver, kidney, cardiac, or pulmonary disease;

2. A terminal medical diagnosis consistent with survival < 1 year;

3. Coexistent major neurological or psychiatric disease as to decrease number of confounders;

4. A history of significant alcohol or drug abuse in the prior 6 months;

5. Use of carbamazepine and amitriptyline;

6. Subjects may not be actively enrolled in a separate intervention study targeting stroke recovery and

7. Subjects may not have already received constraint induced motor therapy and/or tDCS treatment for stroke;

8. History of epilepsy before stroke (or episodes of seizures within the last six months).

9. Subjects with global aphasia and deficits of comprehension

10. Pregnancy

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Spaulding Rehabilitation Hospital	Boston	Massachusetts	United States	02114

Sponsors and Collaborators

• Spaulding Rehabilitation Hospital

Investigators

• Principal Investigator: Felipe Fregni, PhD, Spaulding Rehabilitation Hospital

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Felipe Fregni, Principal Investigator, Spaulding Rehabilitation Hospital
• ClinicalTrials.gov Identifier: NCT01143649
• Other Study ID Numbers: 2009p001808
• First Posted: Jun 14, 2010
• Last Update Posted: Apr 24, 2020
• Last Verified: Apr 1, 2020

• Keywords provided by Felipe Fregni, Principal Investigator, Spaulding Rehabilitation Hospital: Stroke; Transcranial direct current stimulation; Motor function
• Additional relevant MeSH terms: Stroke

Study Results

Participant Flow

Arm/Group Title	tDCS + CIMT - Stroke	Sham tDCS + CIMT - Stroke	Healthy Participants: Active tDCS + Motor Training	Healthy Participants: Sham tDCS + Motor Training	Healthy Participants - Active tACS, Then Sham	Healthy Participants - Sham tACS, Then Active
Arm/Group Description	Participants will receive tDCS over the primary motor cortex (M1). We will use the following stimulation parameters: intensity of 1mA and for the first 40 minutes of constraint induced movement therapy (CIMT- 10 consecutive sessions Monday- Friday). Transcranial Stimulation: Subjects will be stimulated at 1 mA for 40 minutes.	Participants will receive tDCS over the primary motor cortex (M1). We will use the following stimulation parameters: intensity of 1mA and for the first 40 minutes of constraint induced movement therapy (CIMT- 10 consecutive sessions Monday- Friday). Sham stimulation consists of 30secondes of stimulation at the beginning of the 40minutes treatment.	Each stimulation day will include up to six hours of training termed "shaping" in the non-dominant hand while the dominant hand is restrained in a resting hand splint and secured in a sling. At the start of this training, subjects will undergo 40 minutes of tDCS at 1mA.	Each stimulation day will include up to six hours of training termed "shaping" in the non-dominant hand while the dominant hand is restrained in a resting hand splint and secured in a sling. At the start of this training, subjects will undergo 40 minutes of sham tDCS.	Subjects will receive 20 min of active then sham tACS over the primary motor cortex in a randomized order.	Subjects will receive 20 min of sham and then tACS over the primary motor cortex in a randomized order.
Period Title: Overall Study
STARTED	7	7	10	10	5	5
COMPLETED	7	7	10	10	4	3
NOT COMPLETED	0	0	0	0	1	2

Baseline Characteristics

Arm/Group Title	tDCS + CIMT - Stroke	Sham tDCS + CIMT - Stroke	tDCS Active + CIMT - Healthy	Sham tDCS + CIMT - Healthy	tACS Active&Sham - Healthy	Total
Arm/Group Description	Participants received active tDCS over the primary motor cortex (M1). We used the following stimulation parameters: intensity of 1mA and for the first 40 minutes of constraint induced movement therapy (CIMT- 10 consecutive sessions Monday- Friday). Transcranial Stimulation: Subjects were stimulated at 1 mA for 40 minutes.	Participants received sham tDCS over the primary motor cortex plus CIMT. The same site and parameters of stimulation were employed, but the stimulator was turned off after 30 seconds of stimulation. This ensured that patients could feel the initial itching sensation at the beginning of tDCS.	Participants received active (1mA - 40min) of the primary motor cortex (M1) bilaterally combined with unilateral motor training and contralateral hand restraint.	Participants received sham tDCS (1mA - 40min) of the primary motor cortex (M1) bilaterally combined with unilateral motor training and contralateral hand restraint.	active or sham 15Hz-tACS over of the primary motor cortex (M1) bilaterally.	Total of all reporting groups
Overall Participants	7	7	10	10	10	44
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Between 18 and 65 years	7 100%	6 85.7%	10 100%	10 100%	10 100%	43 97.7%
>=65 years	0 0%	1 14.3%	0 0%	0 0%	0 0%	1 2.3%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	42.5 (12.8)	50.8 (14.9)	20.4 (1.7)	20.4 (1.7)	35.83 (18.65)	35.75 (11.69)
Sex: Female, Male (Count of Participants)
Female	4 57.1%	5 71.4%	7 70%	7 70%	4 40%	27 61.4%
Male	3 42.9%	2 28.6%	3 30%	3 30%	6 60%	17 38.6%

Outcome Measures

1. Primary Outcome

Title	Jebsen Taylor Hand Function Test
Description	Jebsen Taylor Hand Function Test: measures hand function in real-life activities, by evaluating the time required to perform 7 different tasks. We used the non-cronstrained hand for the assessments. The sum of the different tasks was used for the analysis.
Time Frame	2 weeks

Outcome Measure Data

Analysis Population Description

The Jebsen Taylor Hand Function Test was only performed in the stroke study (Experiment 1).

Arm/Group Title	tDCS + CIMT	Sham tDCS + CIMT
Arm/Group Description	Participants will receive tDCS over the primary motor cortex (M1). We will use the following stimulation parameters: intensity of 1mA and for the first 40 minutes of constraint induced movement therapy (CIMT- 10 consecutive sessions Monday- Friday). Transcranial Stimulation: Subjects will be stimulated at 1 mA for 40 minutes.	Participants received sham tDCS over the primary motor cortex plus CIMT. The same site and parameters of stimulation were employed, but the stimulator was turned off after 30 seconds of stimulation. This ensured that patients could feel the initial itching sensation at the beginning of tDCS.
Measure Participants	7	7
Mean (Standard Error) [seconds]	68 (34)	80 (42)

2. Primary Outcome

Title	Cortical Excitability
Description	Motor evoked potential (MEP) Using Transcranial Magnetic Stimulation (TMS), MEP were recorded before and after tDCS (both active and sham). The percentage of change in MEP (post versus pre intervention) between the two groups (active and sham) were used for the comparison.
Time Frame	1 hour

Outcome Measure Data

Analysis Population Description

The cortical excitability measurement (MEP) was performed in healthy participants involved in the tDCS+CIMT study (Experiment 2).

Arm/Group Title	Healthy Participants: Active tDCS + Motor Training	Healthy Participants: Sham tDCS + Motor Training
Arm/Group Description	Each stimulation day will include up to six hours of training termed "shaping" in the non-dominant hand while the dominant hand is restrained in a resting hand splint and secured in a sling. At the start of this training, subjects will undergo 40 minutes of tDCS at 1mA.	Each stimulation day will include up to six hours of training termed "shaping" in the non-dominant hand while the dominant hand is restrained in a resting hand splint and secured in a sling. At the start of this training, subjects will undergo 40 minutes of sham tDCS.
Measure Participants	20	20
Mean (Standard Deviation) [percent change]	19.8 (21.4)	0.8 (8.3)

3. Primary Outcome

Title	Cortical Oscillations - EEG
Description	Recording took place in a dim-lighted room set up with acoustic and electric isolation. EEG was acquired from 64-channels HydroCel Geodesic Sensor Net (Electrical Geodesic Inc., Eugene, OH) and recorded using Net Station running on a MacIntosh G4 computer. Alpha power were used as the main outcome measure. The difference values (e.g., post minus pre tACS) were used for the analysis. The alpha frequency is a brain oscillation that takes place especially when subjects are in a relaxed state, especially eyes closed. In the motor cortex, a decrease in alpha power has been seen during motor performance. Therefore, it could be speculated that a decrease in power in this study would indicate more engagement in motor cortex during the motor performance.
Time Frame	15 minutes

Outcome Measure Data

Analysis Population Description

The brain oscillations measurements were only performed in the tACS study (Experiment 3).

Arm/Group Title	Healthy Participants - Active tACS	Healthy Participants - Sham tACS
Arm/Group Description	Subjects will receive 20 min of active tACS	Subjects will receive 20 min of sham tACS
Measure Participants	7	7
Mean (Standard Deviation) [microVolt^2]	-0.03 (0.24)	0.07 (0.16)

Adverse Events

Arm/Group Title	tDCS + CIMT - Stroke		Sham tDCS + CIMT - Stroke		Active tDCS + CIMT - Healthy		Sham tDCS + CIMT - Healthy		Active tACS - Healthy		Sham tACS - Healthy
Arm/Group Description	Participants will receive tDCS over the primary motor cortex (M1). We will use the following stimulation parameters: intensity of 1mA and for the first 40 minutes of constraint induced movement therapy (CIMT- 10 consecutive sessions Monday- Friday). Transcranial Stimulation: Subjects will be stimulated at 1 mA for 40 minutes.		Participants received sham tDCS over the primary motor cortex plus CIMT. The same site and parameters of stimulation were employed, but the stimulator was turned off after 30 seconds of stimulation. This ensured that patients could feel the initial itching sensation at the beginning of tDCS.		subjects will undergo 40 minutes of tDCS at 1mA.		subjects will undergo 40 minutes of sham tDCS.		Subjects will undergo 20 minutes of active tACS.		Subjects will undergo 20 minutes of sham tACS.
All Cause Mortality
	tDCS + CIMT - Stroke		Sham tDCS + CIMT - Stroke		Active tDCS + CIMT - Healthy		Sham tDCS + CIMT - Healthy		Active tACS - Healthy		Sham tACS - Healthy
	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	/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	tDCS + CIMT - Stroke		Sham tDCS + CIMT - Stroke		Active tDCS + CIMT - Healthy		Sham tDCS + CIMT - Healthy		Active tACS - Healthy		Sham tACS - Healthy
	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	0/7 (0%)		0/7 (0%)		0/10 (0%)		0/10 (0%)		0/10 (0%)		0/10 (0%)
Other (Not Including Serious) Adverse Events
	tDCS + CIMT - Stroke		Sham tDCS + CIMT - Stroke		Active tDCS + CIMT - Healthy		Sham tDCS + CIMT - Healthy		Active tACS - Healthy		Sham tACS - Healthy
	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	0/7 (0%)		0/7 (0%)		0/10 (0%)		0/10 (0%)		0/10 (0%)		0/10 (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.