Effects of Combined Spinal Direct Current Stimulation on Upper Limb Recovery in Acquired Brain Injury

Study Overview
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Brief Summary
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This study will compare different polarities of transcutaneous spinal direct current stimulation combined with robotic-assisted arm training (RAT) in adults with acquired brain injury (ABI). Participants will receive 20 minutes of 2.5 milliamps (mA) anodal, cathodal, and sham transpinal direct current stimulation (tsDCS) over cervical spine combined with high intensity robotic-assisted arm training, five days a week, for 2 consecutive weeks.

Detailed Description
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Acquired brain injury (ABI) is the leading cause of neurological disability in the United States and accounts for the poor physical health and the social dysfunction evident in survivors. Hemiparesis due to acquired brain injury is the primary cause of disability and arm paresis is perceived as the primary cause of disability by individuals who have suffered ABI because of the limitations it creates in performing activities of daily living (ADL). Rehabilitation of the impaired limb is essential for improving motor function after ABI, yet only 31% of ABI survivors receive outpatient rehabilitation. Therefore, effective therapy for upper-limb paresis must be addressed. Approximately 80% of all ABI survivors suffer from upper limb paresis and only 18% of these individuals gain full motor recovery with conventional treatments in the year following ABI. The study will use cross-over, randomized, sham controlled, double-blinded design. Participants with subacute or chronic ABI will each be assigned to receive active anodal spinal stimulation, active cathodal spinal stimulation, and sham spinal stimulation for the same duration, and the order that each participant will receive anodal, cathodal, and sham stimulation will be randomized. In all the experiments participants will receive robotic assisted training for duration of 1.5 hours. The first 20 minutes of training will be coupled with spinal stimulation. Treatment will be administered at an intensity of 5 sessions per week for 2 weeks.

Official Title
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Effects of Combined Spinal Direct Current Stimulation on Upper Limb Recovery in Acquired Brain Injury (ABI)

Conditions
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Acquired Brain Injury

Intervention / Treatment
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* Device: tsDCS-Anodal Stimulation
* Device: tsDCS-Cathodal Stimulation
* Device: tsDCS-Sham Stimulation
* Device: Robotic-assisted training of arm and hand functions


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Providing written informed consent prior to any study related procedures; Age above 18; Diagnosis of acquired brain injury at least for 6 month No neuropsychiatric comorbidities Not being involved in any specific exercise program (e.g., neuromuscular electrical stimulation (NMES), functional electrical stimulation (FES)) within the previous 3 months; No planned alteration in upper-extremity therapy or medication for muscle tone during the course of the study; Eligibility for standard upper-extremity rehabilitation at the time of enrollment (i.e., absence medical comorbidities that would prevent standard rehabilitation); No condition (e.g., severe arthritis, extreme shoulder pain) that would interfere with valid administration of the measures or with interpreting motor testing; No contraindications to tsDCS: metal in the head between stimulation area metal in the spine between stimulation area implanted brain medical devices No pregnancy; No contraindications for Transcranial Magnetic Stimulation (TMS) and magnetic resonance imaging (MRI) based on TMS and MRI screening forms Exclusion Criteria: Uncontrolled epilepsy; Any joint contracture or severe spasticity in the affected upper extremity, as measured by a Modified Ashworth Score > than 3 out of 4; History of substance abuse; Subject who cannot provide self-transportation to the study location

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Interventional Model Description: Each participant will receive active anodal spinal stimulation, active cathodal spinal stimulation, and sham spinal stimulation. The order that each participant receives anodal, cathodal, and sham stimulation will be randomized.
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: tsDCS-Anodal & robotic arm training (RAT), then tsDCS-Cathodal & RAT, then tsDCS-Sham & RAT<br>anodal tsDCS over cervical spine, 2.5mA for 20 minutes | Device: tsDCS-Anodal Stimulation<br>* 2.5mA anodal tsDCS over cervical spine for 20 minutes, five days a week, for two weeks. tsDCS electrodes will be placed over cervical spine and shoulder.<br>* Other names: Transcutaneous Spinal Direct Current Stimulation;Device: tsDCS-Cathodal Stimulation<br>* 2.5mA cathodal tsDCS over cervical spine for 20 minutes, five days a week, for two weeks. tsDCS electrodes will be placed over cervical spine and shoulder.<br>* Other names: Transcutaneous Spinal Direct Current Stimulation;Device: tsDCS-Sham Stimulation<br>* 2.5mA sham tsDCS over cervical spine for 20 minutes, five days a week, for two weeks. tsDCS electrodes will be placed over cervical spine and shoulder.<br>* Other names: Transcutaneous Spinal Direct Current Stimulation;Device: Robotic-assisted training of arm and hand functions<br>* 70 minutes of robotic-assisted training (RAT) of arm and hand functions will follow each of the tsDCS sessions, five days a week, for two weeks. Robotic-assisted training will be provided by using the MAHI Exo-II device.<br>|
| Experimental: tsDCS-Anodal & robotic arm training (RAT), then tsDCS-Sham & RAT, then tsDCS-Cathodal & RAT<br>cathodal tsDCS over cervical spine, 2.5mA for 20 minutes | Device: tsDCS-Anodal Stimulation<br>* 2.5mA anodal tsDCS over cervical spine for 20 minutes, five days a week, for two weeks. tsDCS electrodes will be placed over cervical spine and shoulder.<br>* Other names: Transcutaneous Spinal Direct Current Stimulation;Device: tsDCS-Cathodal Stimulation<br>* 2.5mA cathodal tsDCS over cervical spine for 20 minutes, five days a week, for two weeks. tsDCS electrodes will be placed over cervical spine and shoulder.<br>* Other names: Transcutaneous Spinal Direct Current Stimulation;Device: tsDCS-Sham Stimulation<br>* 2.5mA sham tsDCS over cervical spine for 20 minutes, five days a week, for two weeks. tsDCS electrodes will be placed over cervical spine and shoulder.<br>* Other names: Transcutaneous Spinal Direct Current Stimulation;Device: Robotic-assisted training of arm and hand functions<br>* 70 minutes of robotic-assisted training (RAT) of arm and hand functions will follow each of the tsDCS sessions, five days a week, for two weeks. Robotic-assisted training will be provided by using the MAHI Exo-II device.<br>|
| Experimental: tsDCS-Cathodal & robotic arm training (RAT), then tsDCS-Anodal & RAT, then tsDCS-Sham & RAT<br>sham tsDCS over cervical spine, 2.5mA for 20 minutes | Device: tsDCS-Anodal Stimulation<br>* 2.5mA anodal tsDCS over cervical spine for 20 minutes, five days a week, for two weeks. tsDCS electrodes will be placed over cervical spine and shoulder.<br>* Other names: Transcutaneous Spinal Direct Current Stimulation;Device: tsDCS-Cathodal Stimulation<br>* 2.5mA cathodal tsDCS over cervical spine for 20 minutes, five days a week, for two weeks. tsDCS electrodes will be placed over cervical spine and shoulder.<br>* Other names: Transcutaneous Spinal Direct Current Stimulation;Device: tsDCS-Sham Stimulation<br>* 2.5mA sham tsDCS over cervical spine for 20 minutes, five days a week, for two weeks. tsDCS electrodes will be placed over cervical spine and shoulder.<br>* Other names: Transcutaneous Spinal Direct Current Stimulation;Device: Robotic-assisted training of arm and hand functions<br>* 70 minutes of robotic-assisted training (RAT) of arm and hand functions will follow each of the tsDCS sessions, five days a week, for two weeks. Robotic-assisted training will be provided by using the MAHI Exo-II device.<br>|
| Experimental: tsDCS-Cathodal & robotic arm training (RAT), then tsDCS-Sham & RAT, then tsDCS-Anodal & RAT<br> | Device: tsDCS-Anodal Stimulation<br>* 2.5mA anodal tsDCS over cervical spine for 20 minutes, five days a week, for two weeks. tsDCS electrodes will be placed over cervical spine and shoulder.<br>* Other names: Transcutaneous Spinal Direct Current Stimulation;Device: tsDCS-Cathodal Stimulation<br>* 2.5mA cathodal tsDCS over cervical spine for 20 minutes, five days a week, for two weeks. tsDCS electrodes will be placed over cervical spine and shoulder.<br>* Other names: Transcutaneous Spinal Direct Current Stimulation;Device: tsDCS-Sham Stimulation<br>* 2.5mA sham tsDCS over cervical spine for 20 minutes, five days a week, for two weeks. tsDCS electrodes will be placed over cervical spine and shoulder.<br>* Other names: Transcutaneous Spinal Direct Current Stimulation;Device: Robotic-assisted training of arm and hand functions<br>* 70 minutes of robotic-assisted training (RAT) of arm and hand functions will follow each of the tsDCS sessions, five days a week, for two weeks. Robotic-assisted training will be provided by using the MAHI Exo-II device.<br>|
| Experimental: tsDCS-Sham & robotic arm training (RAT), then tsDCS-Anodal & RAT, then tsDCS- Cathodal & RAT<br> | Device: tsDCS-Anodal Stimulation<br>* 2.5mA anodal tsDCS over cervical spine for 20 minutes, five days a week, for two weeks. tsDCS electrodes will be placed over cervical spine and shoulder.<br>* Other names: Transcutaneous Spinal Direct Current Stimulation;Device: tsDCS-Cathodal Stimulation<br>* 2.5mA cathodal tsDCS over cervical spine for 20 minutes, five days a week, for two weeks. tsDCS electrodes will be placed over cervical spine and shoulder.<br>* Other names: Transcutaneous Spinal Direct Current Stimulation;Device: tsDCS-Sham Stimulation<br>* 2.5mA sham tsDCS over cervical spine for 20 minutes, five days a week, for two weeks. tsDCS electrodes will be placed over cervical spine and shoulder.<br>* Other names: Transcutaneous Spinal Direct Current Stimulation;Device: Robotic-assisted training of arm and hand functions<br>* 70 minutes of robotic-assisted training (RAT) of arm and hand functions will follow each of the tsDCS sessions, five days a week, for two weeks. Robotic-assisted training will be provided by using the MAHI Exo-II device.<br>|
| Experimental: tsDCS-Sham & robotic arm training (RAT), then tsDCS-Cathodal & RAT, then tsDCS-Anodal & RAT<br> | Device: tsDCS-Anodal Stimulation<br>* 2.5mA anodal tsDCS over cervical spine for 20 minutes, five days a week, for two weeks. tsDCS electrodes will be placed over cervical spine and shoulder.<br>* Other names: Transcutaneous Spinal Direct Current Stimulation;Device: tsDCS-Cathodal Stimulation<br>* 2.5mA cathodal tsDCS over cervical spine for 20 minutes, five days a week, for two weeks. tsDCS electrodes will be placed over cervical spine and shoulder.<br>* Other names: Transcutaneous Spinal Direct Current Stimulation;Device: tsDCS-Sham Stimulation<br>* 2.5mA sham tsDCS over cervical spine for 20 minutes, five days a week, for two weeks. tsDCS electrodes will be placed over cervical spine and shoulder.<br>* Other names: Transcutaneous Spinal Direct Current Stimulation;Device: Robotic-assisted training of arm and hand functions<br>* 70 minutes of robotic-assisted training (RAT) of arm and hand functions will follow each of the tsDCS sessions, five days a week, for two weeks. Robotic-assisted training will be provided by using the MAHI Exo-II device.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Fugl-Meyer Arm (FMA) Motor Score | FMA is a stroke-specific, performance based impairment index. It quantitatively measures impairment based on Twitchell and Brunnstrom's concept of sequential stages of motor return in hemiplegic stroke patients. It uses an ordinal scale for scoring of 33 items for the upper limb component of the F-M scale (0:can not perform; 1:can perform partially; 2:can perform fully). Total range is 0-66, 0 being poor and 66 normal. | baseline | 
| Fugl-Meyer Arm (FMA) Motor Score | FMA is a stroke-specific, performance based impairment index. It quantitatively measures impairment based on Twitchell and Brunnstrom's concept of sequential stages of motor return in hemiplegic stroke patients. It uses an ordinal scale for scoring of 33 items for the upper limb component of the F-M scale (0:can not perform; 1:can perform partially; 2:can perform fully). Total range is 0-66, 0 being poor and 66 normal. | 2 weeks | 
| Fugl-Meyer Arm (FMA) Motor Score | FMA is a stroke-specific, performance based impairment index. It quantitatively measures impairment based on Twitchell and Brunnstrom's concept of sequential stages of motor return in hemiplegic stroke patients. It uses an ordinal scale for scoring of 33 items for the upper limb component of the F-M scale (0:can not perform; 1:can perform partially; 2:can perform fully). Total range is 0-66, 0 being poor and 66 normal. | 1 month | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Jebsen Taylor Hand Function Test (JTHFT) | The JTHFT is a motor performance test and assesses the time needed to perform 7 everyday activities (for example, flipping cards and feeding). Score is reported as items completed per second. | Baseline | 
| Action Research Arm Test (ARAT) | The ARAT is used to assess subject's ability to manipulate-lift-release objects horizontally and vertically, which differs in size, weight and shape. The test consists of 19 items divided into 4 sub-tests (grasp, grip, pinch, gross arm movement) and each item is rated on a 4-point scale. The possible total score ranges between 0-57. Higher scores indicate better performance. | Baseline | 
| Motor Activity Log (MAL) | The MAL ranges from 0 to 5, with a higher score indicating greater ability to use the affected arm. | Baseline | 
| Pinch Strength | A pinch gauge will be used to measure maximum pinch force. | Baseline | 
| Quantitative Movement Measurement | Robotic movement data will be used to quantitatively measure changes in movement smoothness | Change from baseline at 2 weeks and at 1 month | 
| Number of Participants With Adverse Effects Related to tsDCS | Safety will be measured by questioning and observing participants at each treatment session. Adverse effects, such as skin redness etc. will be recorded. | Baseline | 
| Jebsen Taylor Hand Function Test (JTHFT) | The JTHFT is a motor performance test and assesses the time needed to perform 7 everyday activities (for example, flipping cards and feeding). Score is reported as items completed per second. | 2 weeks | 
| Jebsen Taylor Hand Function Test (JTHFT) | The JTHFT is a motor performance test and assesses the time needed to perform 7 everyday activities (for example, flipping cards and feeding). Score is reported as items completed per second. | 1 month | 
| Action Research Arm Test (ARAT) | The ARAT is used to assess subject's ability to manipulate-lift-release objects horizontally and vertically, which differs in size, weight and shape. The test consists of 19 items divided into 4 sub-tests (grasp, grip, pinch, gross arm movement) and each item is rated on a 4-point scale. The possible total score ranges between 0-57. Higher scores indicate better performance. | 2 weeks | 
| Action Research Arm Test (ARAT) | The ARAT is used to assess subject's ability to manipulate-lift-release objects horizontally and vertically, which differs in size, weight and shape. The test consists of 19 items divided into 4 sub-tests (grasp, grip, pinch, gross arm movement) and each item is rated on a 4-point scale. The possible total score ranges between 0-57. Higher scores indicate better performance. | 1 month | 
| Motor Activity Log (MAL) | The MAL ranges from 0 to 5, with a higher score indicating greater ability to use the affected arm. | 2 weeks | 
| Motor Activity Log (MAL) | The MAL ranges from 0 to 5, with a higher score indicating greater ability to use the affected arm. | 1 month | 
| Number of Participants With Adverse Effects Related to tsDCS | Safety will be measured by questioning and observing participants at each treatment session. Adverse effects, such as skin redness etc. will be recorded. | 2 weeks | 
| Number of Participants With Adverse Effects Related to tsDCS | Safety will be measured by questioning and observing participants at each treatment session. Adverse effects, such as skin redness etc. will be recorded. | 1 month | 
| Pinch Strength | A pinch gauge will be used to measure maximum pinch force. | 2 weeks | 
| Pinch Strength | A pinch gauge will be used to measure maximum pinch force. | 1 month | 
| Grip Strength | A grip dynamometer will be used to measure maximum gross grasp force. | baseline | 
| Grip Strength | A grip dynamometer will be used to measure maximum gross grasp force. | 2 weeks | 
| Grip Strength | A grip dynamometer will be used to measure maximum gross grasp force. | 1 month | 
| Spasticity as Assessed by the Modified Ashworth Scale (MAS) | This test measures spasticity in patients with lesions of the Central Nervous System by testing resistance to passive movement about a joint with varying degrees of velocity. Scores range from 0-4, with 0 indicating normal muscle tone and 4 indicating very high spasticity. The investigators will measure spasticity in the trained upper limb. | baseline | 
| Spasticity as Assessed by the Modified Ashworth Scale (MAS) | This test measures spasticity in patients with lesions of the Central Nervous System by testing resistance to passive movement about a joint with varying degrees of velocity. Scores range from 0-4, with 0 indicating normal muscle tone and 4 indicating very high spasticity. The investigators will measure spasticity in the trained upper limb. | 2 weeks | 
| Spasticity as Assessed by the Modified Ashworth Scale (MAS) | This test measures spasticity in patients with lesions of the Central Nervous System by testing resistance to passive movement about a joint with varying degrees of velocity. Scores range from 0-4, with 0 indicating normal muscle tone and 4 indicating very high spasticity. The investigators will measure spasticity in the trained upper limb. | 1 month | 
| Spinal Reflexes |  | Change from baseline at 2 weeks and at 1 month | 
| Change in Strength of Selective Muscle Groups |  | Change from baseline at 2 weeks and at 1 month | 
| Neurophysiologic Testing for Spinal Conductivity (SSEP) |  | Change from baseline at 2 weeks and at 1 month |