Robots Paired With tDCS in Stroke Recovery

• Sponsor: Northwell Health (Other)
• Overall Status: Completed
• CT.gov ID: NCT01726673
• Collaborator: (none)
• Enrollment: 54
• Location: 1
• Arms: 2
• Actual Duration (Months): 69
• Patients Per Site Per Month: 0.8

Study Details

Study Description

Brief Summary

The purpose of this study is to evaluate if multiple therapy sessions of Transcranial Direct Current Stimulation (tDCS non-invasive brain stimulation) combined with robotic arm therapy lead to a greater functional recovery in upper limb mobility after stroke than that provided by robotic arm therapy alone.

Condition or Disease	Intervention/Treatment	Phase
Stroke	Device: Transcranial Direct Current Stimulation (tDCS); Device: Placebo sham	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 54 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Effects of Transcranial Direct Current Stimulation Paired With Robotic Arm Therapy on Recovery of Upper Extremity Motor Function in Stroke Patients
• Actual Study Start Date: Sep 1, 2012
• Actual Primary Completion Date: Jan 1, 2018
• Actual Study Completion Date: Jun 1, 2018

Arms and Interventions

Arm	Intervention/Treatment
Experimental: tDCS + robotic arm therapy Transcranial Direct Current Stimulation (tDCS) 2mA for 20 minutes over the primary motor cortex (M1) in the affected hemisphere immediately followed by robotic arm therapy for 60 minutes, 3x per week for 12 weeks (36 sessions total)	Device: Transcranial Direct Current Stimulation (tDCS); Other Names: tDCS Low intensity transcranial DC stimulator Soterix 1x1
Placebo Comparator: tDCS sham + robotic arm therapy Transcranial Direct Current Stimulation sham condition (0 mA) for 20 minutes over the primary motor cortex (M1) in the affected hemisphere immediately followed by robotic arm therapy for 60 minutes, 3x per week for 12 weeks (36 sessions total)	Device: Placebo sham; Other Names: tDCS sham

Outcome Measures

Primary Outcome Measures

1. Median Change in Upper Extremity Fugl Meyer Assessment Score [baseline, discharge at 12 weeks (immediately following the intervention), and follow-up at 36 weeks (6 months after the intervention)]

   The median change in Upper Extremity Fugl-Meyer Score was calculated from baseline to discharge at 12 weeks (immediately following the intervention) and again at 36 weeks (6 months follow-up from the intervention) in each training condition (sham tDCS + robotics arm training vs. active tDCS + robotic arm training). The total Upper Extremity Fugl Meyer score is reported, with a range 0-66 points, and with higher values indicating better functional status.

Secondary Outcome Measures

1. Median Change in WOLF Motor Function Test (WMFT) [baseline, discharge at 12 weeks (immediately following the intervention), and follow-up at 36 weeks (6 months after the intervention)]

   The median change in performance time for the WOLF motor function test was calculated from baseline to discharge at 12 weeks (immediately following the intervention) and again at 36 weeks (6 months follow-up from the intervention) in each training condition (sham tDCS + robotics arm training vs. active tDCS + robotic arm training). The total WOLF motor function timed score is reported here in seconds, with a range 0-1800 seconds, and with lower values indicating faster completion of task and better functional status.

2. Median Change in Motor Power Manual Muscle Test Score for the Upper Extremity (MRC) [12 weeks (immediately following the intervention) and 36 weeks (6 months after the intervention)]

   The median change in Motor Power Manual Muscle Test Score for the upper extremity was calculated from baseline to discharge at 12 weeks (immediately following the intervention) and again at 36 weeks (6 months follow-up from the intervention) in each training condition (sham tDCS + robotics arm training vs. active tDCS + robotic arm training). The total Motor Power Manual Muscle Test Score is reported here, with a range 0-100 points, and with higher values indicating better functional status.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• 18 years of age or older

• First single focal unilateral lesion with diagnosis verified by brain imaging, which occurred at least 6 months prior

• Cognitive function sufficient enough to understand experiments and follow instructions

• Fugl-Meyer assessment of 7 to 58 out of 66 (neither hemiplegic nor fully recovered motor function in the muscles of the shoulder, elbow, and wrist)

Exclusion Criteria:

• Botox treatment within 6 weeks of enrollment

• Fixed contraction of the affected limb

• Complete flaccid paralysis of the affected limb

• History of hemorrhagic stroke

• Ongoing use of CNS active medications

• Ongoing use of psychoactive medications

• Presence of additional potential tDCS/TMS risk factors including damaged skin at site of stimulation, presence of a magnetically/mechanically active implant, metal in the head, family history of epilepsy, and personal history of seizures

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Feinstein Institute for Medical Research	Manhasset	New York	United States	11030

Sponsors and Collaborators

• Northwell Health

Investigators

• Principal Investigator: Bruce T Volpe, MD, Feinstein Institute for Medical Research

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Jan 26, 2016

More Information

Publications

• Edwards DJ, Krebs HI, Rykman A, Zipse J, Thickbroom GW, Mastaglia FL, Pascual-Leone A, Volpe BT. Raised corticomotor excitability of M1 forearm area following anodal tDCS is sustained during robotic wrist therapy in chronic stroke. Restor Neurol Neurosci. 2009;27(3):199-207. doi: 10.3233/RNN-2009-0470.

• Responsible Party: Bruce Volpe, Principal Investigator, Northwell Health
• ClinicalTrials.gov Identifier: NCT01726673
• Other Study ID Numbers: 12-102B
• First Posted: Nov 15, 2012
• Last Update Posted: May 14, 2021
• Last Verified: May 1, 2021

• Keywords provided by Bruce Volpe, Principal Investigator, Northwell Health: Stroke; Cerebrovascular Accident; Cerebral Stroke; CVA; Robotic therapy; Upper extremity recovery; tDCS; Non-invasive brain stimulation
• Additional relevant MeSH terms: Stroke

Study Results

Participant Flow

Pre-assignment Detail	Subjects were randomized to receive 36 sessions of either active tDCS immediately followed by robotic arm therapy or sham tDCS immediately followed by robotic arm therapy.

Arm/Group Title	tDCS + Robotic Arm Therapy	tDCS Sham + Robotic Arm Therapy
Arm/Group Description	Transcranial Direct Current Stimulation (tDCS) 2mA for 20 minutes over the primary motor cortex (M1) in the affected hemisphere immediately followed by robotic arm therapy for 60 minutes, 3x per week for 12 weeks (36 sessions total) Transcranial Direct Current Stimulation (tDCS)	Transcranial Direct Current Stimulation sham condition (0 mA) for 20 minutes over the primary motor cortex (M1) in the affected hemisphere immediately followed by robotic arm therapy for 60 minutes, 3x per week for 12 weeks (36 sessions total). Placebo sham
Period Title: Overall Study
STARTED	30	24
COMPLETED	24	21
NOT COMPLETED	6	3

Baseline Characteristics

Arm/Group Title	tDCS + Robotic Arm Therapy	tDCS Sham + Robotic Arm Therapy	Total
Arm/Group Description	Transcranial Direct Current Stimulation (tDCS) 2mA for 20 minutes over the primary motor cortex (M1) in the affected hemisphere immediately followed by robotic arm therapy for 60 minutes, 3x per week for 12 weeks (36 sessions total) Transcranial Direct Current Stimulation (tDCS)	Transcranial Direct Current Stimulation sham condition (0 mA) for 20 minutes over the primary motor cortex (M1) in the affected hemisphere immediately followed by robotic arm therapy for 60 minutes, 3x per week for 12 weeks (36 sessions total) Placebo sham	Total of all reporting groups
Overall Participants	30	24	54
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	20 66.7%	10 41.7%	30 55.6%
>=65 years	10 33.3%	14 58.3%	24 44.4%
Sex: Female, Male (Count of Participants)
Female	11 36.7%	9 37.5%	20 37%
Male	19 63.3%	15 62.5%	34 63%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	3 10%	3 12.5%	6 11.1%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	7 23.3%	3 12.5%	10 18.5%
White	20 66.7%	13 54.2%	33 61.1%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	5 20.8%	5 9.3%

Outcome Measures

1. Primary Outcome

Title	Median Change in Upper Extremity Fugl Meyer Assessment Score
Description	The median change in Upper Extremity Fugl-Meyer Score was calculated from baseline to discharge at 12 weeks (immediately following the intervention) and again at 36 weeks (6 months follow-up from the intervention) in each training condition (sham tDCS + robotics arm training vs. active tDCS + robotic arm training). The total Upper Extremity Fugl Meyer score is reported, with a range 0-66 points, and with higher values indicating better functional status.
Time Frame	baseline, discharge at 12 weeks (immediately following the intervention), and follow-up at 36 weeks (6 months after the intervention)

Outcome Measure Data

Analysis Population Description

45 patients completed 36 sessions (3x/week for 12 weeks) of robotic arm training + sham or active tDCS, and 6 month follow-up at 36 weeks. These 45 participants were consequently included in the efficacy analysis.

Arm/Group Title	tDCS + Robotic Arm Therapy	tDCS Sham + Robotic Arm Therapy
Arm/Group Description	Active Transcranial Direct Current Stimulation (tDCS) 2mA for 20 minutes over the primary motor cortex (M1) in the affected hemisphere immediately followed by robotic arm therapy for 60 minutes, 3x per week for 12 weeks (36 sessions total) Transcranial Direct Current Stimulation (tDCS)	Transcranial Direct Current Stimulation sham condition (0 mA) for 20 minutes over the primary motor cortex (M1) in the affected hemisphere immediately followed by robotic arm therapy for 60 minutes, 3x per week for 12 weeks (36 sessions total). Placebo sham
Measure Participants	24	21
Median change from baseline to discharge at 12 wks	4.5	6.0
Median change from baseline to 6 month follow-up	4	6

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	tDCS + Robotic Arm Therapy, tDCS Sham + Robotic Arm Therapy
	Comments
	Type of Statistical Test	Equivalence
	Comments	Statistical analysis of median change from baseline to DC immediately following 12 weeks of training was assessed with the upper extremity fugl meyer score in the active vs. sham tDCS conditions. Null hypothesis is that there is no difference in median change in upper extremity fugl meyer score between the active and sham tDCS conditions. A significance level of 0.05 was used (two-tailed).
Statistical Test of Hypothesis	p-Value	0.256
	Comments	The Mann-Whitney U test was performed to compare median change in upper extremity fugl meyer score from baseline to 12 weeks (discharge) across two separate study conditions (active vs. sham tDCS).
	Method	Mann-Whitney U test
	Comments
Method of Estimation	Estimation Parameter	U value
	Estimated Value	302
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	tDCS + Robotic Arm Therapy, tDCS Sham + Robotic Arm Therapy
	Comments
	Type of Statistical Test	Equivalence
	Comments	Statistical analysis of median change from baseline to week 36 (6 month follow-up) was assessed with upper extremity fugl meyer score for the active vs. sham tDCS conditions. Null hypothesis is that there is no difference in median change in upper extremity fugl meyer score between the active and sham tDCS conditions. A significance level of 0.05 was used (two-tailed).
Statistical Test of Hypothesis	p-Value	0.222
	Comments	The Mann-Whitney U test was performed to compare median change in upper extremity fugl meyer score from baseline to 36 weeks (follow-up) across two separate study conditions (active vs. sham tDCS).
	Method	Mann-Whitney U test
	Comments
Method of Estimation	Estimation Parameter	U value
	Estimated Value	222
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	Median Change in WOLF Motor Function Test (WMFT)
Description	The median change in performance time for the WOLF motor function test was calculated from baseline to discharge at 12 weeks (immediately following the intervention) and again at 36 weeks (6 months follow-up from the intervention) in each training condition (sham tDCS + robotics arm training vs. active tDCS + robotic arm training). The total WOLF motor function timed score is reported here in seconds, with a range 0-1800 seconds, and with lower values indicating faster completion of task and better functional status.
Time Frame	baseline, discharge at 12 weeks (immediately following the intervention), and follow-up at 36 weeks (6 months after the intervention)

Outcome Measure Data

Analysis Population Description

45 patients completed 36 sessions (3x/week for 12 weeks) of robotic arm training + sham or active tDCS, and 6 month follow-up at 36 weeks. These 45 participants were consequently included in the efficacy analysis.

Arm/Group Title	tDCS + Robotic Arm Therapy	tDCS Sham + Robotic Arm Therapy
Arm/Group Description	Active Transcranial Direct Current Stimulation (tDCS) 2mA for 20 minutes over the primary motor cortex (M1) in the affected hemisphere immediately followed by robotic arm therapy for 60 minutes, 3x per week for 12 weeks (36 sessions total) Transcranial Direct Current Stimulation (tDCS)	Transcranial Direct Current Stimulation sham condition (0 mA) for 20 minutes over the primary motor cortex (M1) in the affected hemisphere immediately followed by robotic arm therapy for 60 minutes, 3x per week for 12 weeks (36 sessions total). Placebo sham
Measure Participants	24	21
Median change from baseline to discharge at 12 wks	-34	-19
Median change from baseline to 6 month follow-up	-103	-81.5

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	tDCS + Robotic Arm Therapy, tDCS Sham + Robotic Arm Therapy
	Comments
	Type of Statistical Test	Equivalence
	Comments	Statistical analysis of median change from baseline to DC immediately following 12 weeks of training was assessed with the WOLF Motor Function test time score (out of 1800 seconds) in the active vs. sham tDCS conditions. Null hypothesis is that there is no difference in median change in WMFT time score between the active and sham tDCS conditions. A significance level of 0.05 was used (two-tailed).
Statistical Test of Hypothesis	p-Value	1.0
	Comments	The Mann-Whitney U test was performed to compare median change in the WMFT time score from baseline to 12 weeks (discharge) across two separate study conditions (active vs. sham tDCS).
	Method	Mann-Whitney U Test
	Comments
Method of Estimation	Estimation Parameter	U Value
	Estimated Value	251.5
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	tDCS + Robotic Arm Therapy, tDCS Sham + Robotic Arm Therapy
	Comments
	Type of Statistical Test	Equivalence
	Comments	Statistical analysis of median change from baseline to week 36 (6 month follow-up) was assessed with the WOLF Motor Function test time score (out of 1800 seconds) in the active vs. sham tDCS conditions. Null hypothesis is that there is no difference in median change in WMFT time score between the active and sham tDCS conditions. A significance level of 0.05 was used (two-tailed).
Statistical Test of Hypothesis	p-Value	0.592
	Comments	The Mann-Whitney U test was performed to compare median change in the WMFT time score from baseline to 36 weeks ( 6 month follow-up) across two separate study conditions (active vs. sham tDCS).
	Method	Mann-Whitney U Test
	Comments
Method of Estimation	Estimation Parameter	U value
	Estimated Value	208.5
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

3. Secondary Outcome

Title	Median Change in Motor Power Manual Muscle Test Score for the Upper Extremity (MRC)
Description	The median change in Motor Power Manual Muscle Test Score for the upper extremity was calculated from baseline to discharge at 12 weeks (immediately following the intervention) and again at 36 weeks (6 months follow-up from the intervention) in each training condition (sham tDCS + robotics arm training vs. active tDCS + robotic arm training). The total Motor Power Manual Muscle Test Score is reported here, with a range 0-100 points, and with higher values indicating better functional status.
Time Frame	12 weeks (immediately following the intervention) and 36 weeks (6 months after the intervention)

Outcome Measure Data

Analysis Population Description

45 patients completed 36 sessions (3x/week for 12 weeks) of robotic arm training + sham or active tDCS, and 6 month follow-up at 36 weeks. These 45 participants were consequently included in the efficacy analysis.

Arm/Group Title	tDCS + Robotic Arm Therapy	tDCS Sham + Robotic Arm Therapy
Arm/Group Description	Active Transcranial Direct Current Stimulation (tDCS) 2mA for 20 minutes over the primary motor cortex (M1) in the affected hemisphere immediately followed by robotic arm therapy for 60 minutes, 3x per week for 12 weeks (36 sessions total) Transcranial Direct Current Stimulation (tDCS)	Transcranial Direct Current Stimulation sham condition (0 mA) for 20 minutes over the primary motor cortex (M1) in the affected hemisphere immediately followed by robotic arm therapy for 60 minutes, 3x per week for 12 weeks (36 sessions total). Placebo sham
Measure Participants	24	21
Median change from baseline to discharge at 12 wks	7	7
Median change from baseline to 6 month follow-up	6	6

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	tDCS + Robotic Arm Therapy, tDCS Sham + Robotic Arm Therapy
	Comments
	Type of Statistical Test	Equivalence
	Comments	Statistical analysis of median change from baseline to DC immediately following 12 weeks of training was assessed with the Motor Power Manual Muscle Test Score for the upper extremity (out of 100 points) in the active vs. sham tDCS conditions. Null hypothesis is that there is no difference in median change in MRC score between the active and sham tDCS conditions. A significance level of 0.05 was used (two-tailed).
Statistical Test of Hypothesis	p-Value	0.680
	Comments	The Mann-Whitney U test was performed to compare median change in the MRC score from baseline to 12 weeks (discharge) across two separate study conditions (active vs. sham tDCS).
	Method	Mann-Whitney U test
	Comments
Method of Estimation	Estimation Parameter	U value
	Estimated Value	270.5
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	tDCS + Robotic Arm Therapy, tDCS Sham + Robotic Arm Therapy
	Comments
	Type of Statistical Test	Equivalence
	Comments	Statistical analysis of median change from baseline to week 36 (6 month FU) was assessed with the Motor Power Manual Muscle Test Score for the upper extremity (out of 100 points) in the active vs. sham tDCS conditions. Null hypothesis is that there is no difference in median change in MRC score between the active and sham tDCS conditions. A significance level of 0.05 was used (two-tailed).
Statistical Test of Hypothesis	p-Value	0.837
	Comments	The Mann-Whitney U test was performed to compare median change in the MRC score from baseline to 6 month FU across two separate study conditions (active vs. sham tDCS).
	Method	Mann-Whitney U Test
	Comments
Method of Estimation	Estimation Parameter	U value
	Estimated Value	187.5
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Adverse Events

Time Frame	Patients were followed for a total of 36 weeks, including the 12 weeks of the study intervention, and the 6 month follow-up period.
Arm/Group Title	tDCS + Robotic Arm Therapy		tDCS Sham + Robotic Arm Therapy
Arm/Group Description	Active Transcranial Direct Current Stimulation (tDCS) 2mA for 20 minutes over the primary motor cortex (M1) in the affected hemisphere immediately followed by robotic arm therapy for 60 minutes, 3x per week for 12 weeks (36 sessions total) Transcranial Direct Current Stimulation (tDCS)		Transcranial Direct Current Stimulation sham condition (0 mA) for 20 minutes over the primary motor cortex (M1) in the affected hemisphere immediately followed by robotic arm therapy for 60 minutes, 3x per week for 12 weeks (36 sessions total). Placebo sham
All Cause Mortality
	tDCS + Robotic Arm Therapy		tDCS Sham + Robotic Arm Therapy
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/30 (0%)		0/24 (0%)
Serious Adverse Events
	tDCS + Robotic Arm Therapy		tDCS Sham + Robotic Arm Therapy
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/30 (0%)		0/24 (0%)
Other (Not Including Serious) Adverse Events
	tDCS + Robotic Arm Therapy		tDCS Sham + Robotic Arm Therapy
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/30 (6.7%)		1/24 (4.2%)
Musculoskeletal and connective tissue disorders
back pain flair up	1/30 (3.3%)	1	0/24 (0%)	0
Nervous system disorders
Myasthenia Gravis	1/30 (3.3%)	1	0/24 (0%)	0
seizure	0/30 (0%)	0	1/24 (4.2%)	1

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.