Improving SCI Rehabilitation Interventions by Retraining the Brain

The Long-term goal of this project is to develop upper limb rehabilitation interventions that can be utilized for cervical Spinal Cord Injury survivors.

This Study will utilize a novel method of non-invasive brain stimulation in conjunction with upper limb training given for 15 sessions over several weeks up to 8 weeks.

The Study will include the following site visits:

• Eligibility Screening and Informed Consent Visit.
• Four testing visit in which motor function of the upper limb and neurophysiology will be measured
• Fifteen intervention visits during which patients will receive upper limb training in conjunction with non-invasive brain stimulation
• Repeat testing of motor function and neurophysiology of the upper limb following completion of intervention visits
• a Follow-up visit completed 3 months after the completion of interventions

Study Overview

• Status: Completed
• Conditions: Cervical Spinal Cord Injruy
• Intervention / Treatment: Device: Active tDCS + task oriented practice; Device: Sham tDCS + task oriented practice

Detailed Description

This is a phase I/II Multi-site Clinical Trial. In this phase I/II randomized controlled study, 49(up to 54) cervical spinal patients with upper limb impairments will receive non-invasive brain stimulation tDCS (Transcranial Direct Current Stimulation) to the area in the brain controlling the weaker muscle of the weakest upper limb while receiving training for 15 sessions over several weeks up to 8 weeks. The primary outcome will be motor limb impairment, and secondary outcomes will be tests of functional ability, spinal excitability, and strength and dexterity. Safety and feasibility of pairing tDCS with rehabilitation will also be explored and include adverse effects, subject/investigator blinding, and attrition to 3 month follow-up.

• Study Type: Interventional
• Enrollment (Actual): 47
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • New Jersey
    • West Orange, New Jersey, United States, 07052
      • Kessler Foundation
  • Ohio
    • Cleveland, Ohio, United States, 44109
      • The MetroHealth System
    • Cleveland, Ohio, United States, 44106
      • Louis B. Stokes Cleveland VA Medical Center
    • Cleveland, Ohio, United States, 44195
      • Lerner Research Institute; Cleveland Clinid Foundation

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Patients with incomplete (having sparing to muscles in the upper extremities below the level of injury) C1-C8 SCI
• at least 1 year post injury
• weakness of the triceps or biceps muscle in the weaker upper limb, defined as a clinically detectable difference in power compared to the power of the spared antagonist(biceps and triceps respectively) muscle, i.e., at least one muscle grade lower on the MRC scale.

Exclusion Criteria:

• contraindications to tDCS and TMS including: pacemaker, metal in the skull, seizure history, pregnancy.
• pressure ulcers
• traumatic brain injury (TBI), diagnosed based upon acute injury Rancho scale <5 or positive MRI/CT findings at the time of injury will also be excluded to prevent confounding of TMS metrics.
• excessive tone/spasticity and severe contractures or soft tissue shortening at the elbow/wrist
• participating in ongoing upper-limb therapies

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Active tDCS + task oriented practice	Device: Active tDCS + task oriented practice; Participants in this arm will receive active tDCS (2mA) to the motor cortex (targeting the triceps) of the weaker upper limb for 2, 30-minute cycles during each 2-hour upper limb training session. While receiving tDCS, the participant will be performing task-oriented practice for the weaker upper limb. Participants will receive these interventions for 15 sessions over several weeks up to 8 weeks.
Sham Comparator: Sham tDCS + task oriented practice	Device: Sham tDCS + task oriented practice; Participants in this arm will receive sham tDCS (0mA) to the motor cortex (targeting the triceps) of the weaker upper limb for 2, 30-minute cycles during each 2-hour upper limb training session. While receiving tDCS, the participant will be performing task-oriented practice for the weaker upper limb. Participants will receive these interventions for 15 sessions over several weeks up to 8 weeks.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Upper Extremity Motor Score (UEMS) With Manual Muscle Testing	UEMS is used in Spinal Cord injury to identify strength (muscle power) in patients with spinal cord injury. It involves a manual muscle test of five key muscles in each arm graded from 0 (no contraction) to 5 (normal strength). Each Arm can have a max score of 25 and the total score for the test is 50 points. The higher the value the more muscle strength the participant has and a higher change score means more improvement. The sum of scores for both arms is reported here.	Baseline (0 weeks), after intervention (up to 8 weeks)
Change in Graded and Redefined Assessment of Strength, Sensibility and Prehension (GRASSP)	Graded and Redefined Assessment of Strength, Sensibility and Prehension (GRASSP) is a functional measure which identifies the functional ability of the upper limbs and is widely used in studies recruiting Spinal Cord Injury patients. It has subsets including strength (100 points total, 50 per arm), palmar and dorsal sensation (48 points total, 24 per arm), prehension ability (24 points total, 12 per arm), and prehension performance (60 points total, 30 per arm). The higher the score the better the performance. The greater the change in score the more the participant improved. The sum of scores for both arms is reported here.	Baseline (0 weeks), after intervention (up to 8 weeks)
Change in Canadian Occupational Performance Measure (COPM) Performance	The Canadian Occupational Performance Measure (COPM) is an evidence-based outcome measure designed to capture the participants self-perception of everyday issues that restrict their participation in everyday living, measuring both their performance in completing the identified task and their satisfaction in their performance of the task. Here we report the performance scale of the assessment. The score range is from minimum 1 (not able to do it at all) and maximum 10 (able to do it extremely well). A larger change score indicates more subjective improvement in performance of activies of daily living.	Baseline (0 weeks), after intervention (up to 8 weeks)
Change in Canadian Occupational Performance Measure (COPM) Satisfaction	The Canadian Occupational Performance Measure (COPM) is an evidence-based outcome measure designed to capture the participants self-perception of everyday issues that restrict their participation in everyday living, measuring both their performance in completing the identified task and their satisfaction in their performance of the task. Here we report the satisfaction scale of the assessment. The score range is from minimum 1 (not satisfied at all) and maximum 10 (extremely satisfied). A larger change score indicates more subjective improvement in satisfaction of completing activies of daily living.	Baseline (0 weeks), after intervention (up to 8 weeks)
Change in Spinal Cord Independence Measure (SCIM), Self-care Subscore	The Spinal Cord Indepence Measure (SCIM) is a participant subjective spinal cord injury measure that identifies daily acitivity indepence. The Self-care subscore of the SCIM looks at independence in performing daily activies and ranges from minimum 0 (total dependence in self-care) to maximum 20 (complete independence in self-care). A higher change score indicates improved levels of independece for the participant.	Baseline (0 weeks), after intervention (up to 8 weeks)
Change in Capabilities of Upper Extremity Test (CUE-T)	The Capabilities of Upper Extremity Test (CUE-T) is a performance based functional measure that evaluates upper extremity function in poeple with cervical spinal cord injury. It consists of 32 items, each item is scored from 0 (unable to complete task) to 4 (no difficulty to complete task). The minimum score of the scale is 0 (unable to performe any of the tasks) to maximum 128 (able to complete every task with no difficulty). A higher change score indicates and improvement in ability to complete upper limb functional tasks.	Baseline (0 weeks), after intervention (up to 8 weeks)
Change in Excitability (Active Motor Threshold) of Cortical and Corticospinal Physiology (TMS), Weaker Arm-Biceps	Transcranial magnetic stimulation was used to test cortical and corticospinal physiology. The active motor threshold (AMT) is the lowest intensity of stimulation needed to produce a motor evoked potential during a voluntary contraction in the biceps muscle. The criteria for defining a motor evoked potential is 6 out of 10 trials in which the response signal is larger peak-to-peak than the background muscle activity by 100µV. The AMT can have a value ranging from 0-100, an indicator of the percentage of the maximum stimulator output (MSO). The higher the value the more stimulation intensity needed to get a criterion motor evoked potential in the target muscle; lower AMT values indicate higher excitability in the muscle. A change score that is negative indicates increased excitability in the biceps muscle.	Baseline (0 weeks) and after intervention (up to 8 weeks)
Change in Excitability (Active Motor Threshold) of Cortical and Corticospinal Physiology (TMS), Weaker Arm Triceps	Transcranial magnetic stimulation was used to test cortical and corticospinal physiology. The active motor threshold (AMT) is the lowest intensity of stimulation needed to produce a motor evoked potential during a voluntary contraction in the triceps muscle. The criteria for defining a motor evoked potential is 6 out of 10 trials in which the response signal is larger peak-to-peak than the background muscle activity by 100µV. The AMT can have a value ranging from 0-100, an indicator of the percentage of the maximum stimulator output (MSO). The higher the value, the more stimulation intensity needed to get a criterion motor evoked potential in the target muscle; lower AMT values indicate higher excitability in the muscle. A change score that is negative indicates increased excitability in the triceps muscle.	Baseline (0 weeks) and after intervention (up to 8 weeks)
Change in Excitability of Spinal Physiology of the Flexor Carpi Radialis Muslce in the Weaker Arm.	Spinal pathways were tested using peripheral nerve stimulation to median nerve to collect responses in the Flexor Carpi Radialis muscle of the weaker arm. This stimulation stimulates both the sensory and motor nerves to produce a evoked potential for each pathway. The evoked potential produced for the sensory pathway is considered the Hoffman reflex (H-reflex) and the evoked potential produced for the motor pathway is considered the muscle compund action potential (M-wave). To get an understanding of the motor neuron pool of exitability we use the H/M ratio which compares the peak amplitude of the maximum H-reflex to the maximum M-wave (H-reflex/M-wave). This ratio reflects the proportion of the motor neruon pool activated by the reflex or motor neuron excitability. A lower H/M ratio generally indicates lower excitability while a higher ratio indicates higher excitability.	Baseline (0 weeks) and after intervention (up to 8 weeks)

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety and Feasibility	In line with this phase I/II clinical trial, safety and feasibility will be tested throughout this study. Vital signs (blood pressure, heart rate, respirations, blood oxygen saturation) will be recorded for each study session. During Intervention sessions we will ask a tDCS adverse effects questionnaire at the end of each session.	Through study completion, an average of 7 months
TMS Safety Questionnaire	A TMS safety questionnaire will be asked at the end of the preintervention tests and the post intervention testing visit.	Baseline (0 weeks) and after intervention (up to 8 weeks)

Collaborators and Investigators

• Sponsor: The Cleveland Clinic
• Collaborators: United States Department of Defense; Congressionally Directed Medical Research Programs
• Investigators: Principal Investigator: Ela Plow, PhD, The Cleveland Clinic

Publications and helpful links

General Publications

• Arora T, O'Laughlin K, Potter-Baker K, Kirshblum S, Kilgore K, Forrest GF, Bryden AM, Wang X, Henzel MK, Li M, Perlic K, Richmond MA, Pundik S, Bethoux F, Frost F, Plow EB. Safety and efficacy of transcranial direct current stimulation in upper extremity rehabilitation after tetraplegia: protocol of a multicenter randomized, clinical trial. Spinal Cord. 2022 Sep;60(9):774-778. doi: 10.1038/s41393-022-00768-z. Epub 2022 Mar 5.

Study record dates

Study Major Dates

• Study Start (Actual): July 12, 2019
• Primary Completion (Actual): September 29, 2024
• Study Completion (Actual): October 9, 2024

Study Registration Dates

• First Submitted: January 17, 2019
• First Submitted That Met QC Criteria: March 26, 2019
• First Posted (Actual): March 27, 2019

Study Record Updates

• Last Update Posted (Estimated): December 10, 2025
• Last Update Submitted That Met QC Criteria: December 3, 2025
• Last Verified: December 1, 2025

More Information

Terms related to this study

• Keywords: Rehabilitation; tDCS; Transcranial Direct Current Stimulation; Upper limb; Cervical Spinal Cord Injury; Brain Stimulation
• Other Study ID Numbers: 18-972; CDMRP-SC170311 (Other Grant/Funding Number: Congressionally Directed Medical Research Program Program (CDMRP), DoD)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes
• product manufactured in and exported from the U.S.: No