Improving SCI Rehabilitation Interventions by Retraining the Brain

NCT03892746 | Completed Phase 1 Results DMC FDA Device

• 2 other identifiers: 18-972CDMRP-SC170311
• Study Type: interventional
• Target: 47
• Locations: 1 country
• Sites: 4

Brief Summary

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

Conditions

Cervical Spinal Cord Injruy

Keywords

Cervical Spinal Cord Injury; tDCS; Transcranial Direct Current Stimulation; Upper limb; Rehabilitation; Brain Stimulation

Outcome Measures

Primary Outcomes (9)

• 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 Outcomes (2)

• Safety and Feasibility

  Through study completion, an average of 7 months

• TMS Safety Questionnaire

  Baseline (0 weeks) and after intervention (up to 8 weeks)

Study Arms (2)

Active tDCS + task oriented practice

ACTIVE COMPARATOR

Device: Active tDCS + task oriented practice

Sham tDCS + task oriented practice

SHAM COMPARATOR

Device: Sham tDCS + task oriented practice

Interventions

Sham tDCS + task oriented practice DEVICE

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.

Sham tDCS + task oriented practice

Active tDCS + task oriented practice DEVICE

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.

Active tDCS + task oriented practice

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• The Cleveland Clinic: lead
• Congressionally Directed Medical Research Programs: collaborator
• United States Department of Defense: collaborator

Study Sites (4)

Kessler Foundation

West Orange, New Jersey, 07052, United States

Location

Louis B. Stokes Cleveland VA Medical Center

Cleveland, Ohio, 44106, United States

Location

The MetroHealth System

Cleveland, Ohio, 44109, United States

Location

Lerner Research Institute; Cleveland Clinid Foundation

Cleveland, Ohio, 44195, United States

Location

Related Publications (1)

• 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.

  PMID: 35246620 DERIVED

Results Point of Contact

• Title: Ela Plow, Associate Professor
• Organization: Cleveland Clinic

plowe2@ccf.org

216-445-4589

Study Officials

• Ela Plow, PhD

  The Cleveland Clinic

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Subjects will be randomly assigned by the Cleveland Clinic biostatistician to receive either active or sham tDCS. The tDCS will be pre-programmed with codes for active and sham stimulation. The code will be given to the intervention team by the biostatistician. Investigators analyzing functional outcome data and neurophysiology data will receive coded data that conceals the identity of the subject.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator, Staff, Neural Control Lab, Dept. of Biomedical Engineering

Model Details: In this phase I/II clinical trial, an anticipated 49(up to 54) subjects will receive 15 sessions of upper limb training while receiving either active tDCS or sham tDCS to the target in the brain devoted to the weaker triceps of the weaker upper limb.

Study Record Dates

• First Submitted: January 17, 2019
• First Posted: March 27, 2019
• Study Start: July 12, 2019
• Primary Completion: September 29, 2024
• Study Completion: October 9, 2024
• Last Updated: December 10, 2025
• Results First Posted: December 2, 2025

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (4)