Restoring Hand Function Utilizing Nerve Transfers in Persons With Cervical Spinal Cord Injuries

Study Overview
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Brief Summary
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The primary objective of this study is to evaluate the safety and efficacy of nerve transfer surgery for restoring hand function as a therapy for patients with cervical spinal cord injury.

Official Title
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Restoring Hand Function Utilizing Nerve Transfers in Persons With Cervical Spinal Cord Injuries

Conditions
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Cervical Spinal Cord Injury, Spinal Cord Injuries, Traumatic Spinal Cord Compression

Intervention / Treatment
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* Procedure: Upper extremity nerve transfer surgery


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: American Spinal Injury Association (ASIA) grade of A, B, or C, or with a diagnosis of central cord syndrome, showing minimal to no evidence of functional improvement in motor examination after at least 6 months of non-operative therapy post-injury >6 months post-injury International Classification of Surgery of the Hand in Tetraplegia (ICSHT) category 0-4 Cervical spinal cord injury resulting in arm & hand functional impairment, with at least preserved elbow flexion Physically and mentally willing and able to comply with study protocol Lives in the immediate area and has no plans to relocate Provides informed consent and HIPAA release of medical information Exclusion Criteria: Active infection Any return or ongoing clinical recovery of distal motor function within 6 months after injury Physically/mentally compromised Systemic disease that would affect the patient's welfare or the research study Immunologically suppressed or immunocompromised Currently undergoing long-term steroid therapy Active malignancy Pending litigation or receiving Workers Compensation related to injury or accident Pregnancy Significant contractures and/or limitations in passive range of motion in the arm or hand Poorly controlled upper extremity spasticity Uncontrolled pain or hypersensitivity Previous or current injury preventing use of tendon transfers to restore upper extremity function History of brachial plexus injury or systemic neuropathic process In the opinion of the Principal Investigator the subject would not be a candidate for the procedure

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Upper extremity nerve transfer surgery<br>Upper extremity nerve transfer surgery is a surgical procedure where axons from an intact, functioning upper extremity peripheral nerve are moved to a target muscle that demonstrates significant weakness or paralysis as a result of spinal cord injury. After allowing time for recovery from surgery and for nerve growth to occur, the patient undergoes hand/occupational therapy in order to retrain motor skills. | Procedure: Upper extremity nerve transfer surgery<br>* Upper extremity nerve transfer surgery is a surgical procedure where axons from an intact, functioning upper extremity peripheral nerve are moved to a target muscle that demonstrates significant weakness or paralysis as a result of spinal cord injury. After allowing time for recovery from surgery and for nerve growth to occur, the patient undergoes hand/occupational therapy in order to retrain motor skills.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Upper extremity muscle strength of right arm as assessed by the Graded Redefined Assessment of Strength, Sensibility, and Prehension (GRASSP) strength subscale | The GRASSP is a measure of upper extremity strength, sensation, and grip that is specific to patients with tetraplegia. It consists of 5 subscales for each upper extremity, and this measure will report the strength subscale (manual muscle testing of 10 muscles in right arm - subscale total score encompasses all 10 muscles). The strength subscale total score ranges from 0 to 50. The GRASSP will be administered by the nurses or physical therapist involved in the study. | Pre-operative | 
| Upper extremity muscle strength of right arm as assessed by the Graded Redefined Assessment of Strength, Sensibility, and Prehension (GRASSP) strength subscale | The GRASSP is a measure of upper extremity strength, sensation, and grip that is specific to patients with tetraplegia. It consists of 5 subscales for each upper extremity, and this measure will report the strength subscale (manual muscle testing of 10 muscles in right arm - subscale total score encompasses all 10 muscles). The strength subscale total score ranges from 0 to 50. The GRASSP will be administered by the nurses or physical therapist involved in the study. | post-operative at 2 weeks | 
| Upper extremity muscle strength of right arm as assessed by the Graded Redefined Assessment of Strength, Sensibility, and Prehension (GRASSP) strength subscale | The GRASSP is a measure of upper extremity strength, sensation, and grip that is specific to patients with tetraplegia. It consists of 5 subscales for each upper extremity, and this measure will report the strength subscale (manual muscle testing of 10 muscles in right arm - subscale total score encompasses all 10 muscles). The strength subscale total score ranges from 0 to 50. The GRASSP will be administered by the nurses or physical therapist involved in the study. | post-operative at 3 months | 
| Upper extremity muscle strength of right arm as assessed by the Graded Redefined Assessment of Strength, Sensibility, and Prehension (GRASSP) strength subscale | The GRASSP is a measure of upper extremity strength, sensation, and grip that is specific to patients with tetraplegia. It consists of 5 subscales for each upper extremity, and this measure will report the strength subscale (manual muscle testing of 10 muscles in right arm - subscale total score encompasses all 10 muscles). The strength subscale total score ranges from 0 to 50. The GRASSP will be administered by the nurses or physical therapist involved in the study. | post-operative at 6 months | 
| Upper extremity muscle strength of right arm as assessed by the Graded Redefined Assessment of Strength, Sensibility, and Prehension (GRASSP) strength subscale | The GRASSP is a measure of upper extremity strength, sensation, and grip that is specific to patients with tetraplegia. It consists of 5 subscales for each upper extremity, and this measure will report the strength subscale (manual muscle testing of 10 muscles in right arm - subscale total score encompasses all 10 muscles). The strength subscale total score ranges from 0 to 50. The GRASSP will be administered by the nurses or physical therapist involved in the study. | post-operative at 12 months | 
| Upper extremity muscle strength of right arm as assessed by the Graded Redefined Assessment of Strength, Sensibility, and Prehension (GRASSP) strength subscale | e GRASSP is a measure of upper extremity strength, sensation, and grip that is specific to patients with tetraplegia. It consists of 5 subscales for each upper extremity, and this measure will report the strength subscale (manual muscle testing of 10 muscles in right arm - subscale total score encompasses all 10 muscles). The strength subscale total score ranges from 0 to 50. The GRASSP will be administered by the nurses or physical therapist involved in the study. | post-operative at 24 months | 
| Upper extremity muscle strength of left arm as assessed by the Graded Redefined Assessment of Strength, Sensibility, and Prehension (GRASSP) strength subscale | The GRASSP is a measure of upper extremity strength, sensation, and grip that is specific to patients with tetraplegia. It consists of 5 subscales for each upper extremity, and this measure will report the strength subscale (manual muscle testing of 10 muscles in left arm - subscale total score encompasses all 10 muscles). The strength subscale total score ranges from 0 to 50. The GRASSP will be administered by the nurses or physical therapist involved in the study. | Pre-operative | 
| Upper extremity muscle strength of left arm as assessed by the Graded Redefined Assessment of Strength, Sensibility, and Prehension (GRASSP) strength subscale | The GRASSP is a measure of upper extremity strength, sensation, and grip that is specific to patients with tetraplegia. It consists of 5 subscales for each upper extremity, and this measure will report the strength subscale (manual muscle testing of 10 muscles in right arm - subscale total score encompasses all 10 muscles). The strength subscale total score ranges from 0 to 50. The GRASSP will be administered by the nurses or physical therapist involved in the study. | post-operative at 2 weeks | 
| Upper extremity muscle strength of left arm as assessed by the Graded Redefined Assessment of Strength, Sensibility, and Prehension (GRASSP) strength subscale | The GRASSP is a measure of upper extremity strength, sensation, and grip that is specific to patients with tetraplegia. It consists of 5 subscales for each upper extremity, and this measure will report the strength subscale (manual muscle testing of 10 muscles in right arm - subscale total score encompasses all 10 muscles). The strength subscale total score ranges from 0 to 50. The GRASSP will be administered by the nurses or physical therapist involved in the study. | post-operative at 3 months | 
| Upper extremity muscle strength of left arm as assessed by the Graded Redefined Assessment of Strength, Sensibility, and Prehension (GRASSP) strength subscale | The GRASSP is a measure of upper extremity strength, sensation, and grip that is specific to patients with tetraplegia. It consists of 5 subscales for each upper extremity, and this measure will report the strength subscale (manual muscle testing of 10 muscles in right arm - subscale total score encompasses all 10 muscles). The strength subscale total score ranges from 0 to 50. The GRASSP will be administered by the nurses or physical therapist involved in the study. | post-operative at 6 months | 
| Upper extremity muscle strength of left arm as assessed by the Graded Redefined Assessment of Strength, Sensibility, and Prehension (GRASSP) strength subscale | The GRASSP is a measure of upper extremity strength, sensation, and grip that is specific to patients with tetraplegia. It consists of 5 subscales for each upper extremity, and this measure will report the strength subscale (manual muscle testing of 10 muscles in right arm - subscale total score encompasses all 10 muscles). The strength subscale total score ranges from 0 to 50. The GRASSP will be administered by the nurses or physical therapist involved in the study. | post-operative at 12 months | 
| Upper extremity muscle strength of left arm as assessed by the Graded Redefined Assessment of Strength, Sensibility, and Prehension (GRASSP) strength subscale | The GRASSP is a measure of upper extremity strength, sensation, and grip that is specific to patients with tetraplegia. It consists of 5 subscales for each upper extremity, and this measure will report the strength subscale (manual muscle testing of 10 muscles in right arm - subscale total score encompasses all 10 muscles). The strength subscale total score ranges from 0 to 50. The GRASSP will be administered by the nurses or physical therapist involved in the study. | post-operative at 24 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Motor neuron signaling as assessed by electromyography (EMG) | Quantitative assessment of motor neuron signalling | Pre-operative, post-operative at 6 months, 1 year, and 2 years | 
| Strength as assessed by Manual Muscle Testing (MMT) | MMT will be assessed by the physicians, nurses, or physical therapist involved in the study. | Pre-operative (5 repeated measurements over 2 months), post-operative at 2 weeks, 3 months, 6 months, 12 months, and 24 months | 
| Strength as assessed by Hand Held Dynamometry (HHD) | Hand held dynamometry (via a make test) will be used to assess strength. | Pre-operative (5 repeated measurements over 2 months), post-operative at 2 weeks, 3 months, 6 months, 12 months, and 24 months | 
| Strength as assessed by the American Spinal Injury Association (ASIA) Upper Extremity Motor Score (UEMS) | The ASIA UEMS is a sum of the motor scores for 5 key upper extremity muscles on both the right and left side (each key muscle is a functionally significant representation of a spinal cord segment). The strength of each key muscle on both the right and left side is graded from 0 to 5, with total scores ranging from 0 to 50.The UEMS will be determined in accordance with the International Standards for Neurological Classification of SCI examination guidelines by the physicians, nurses, or physical therapist. | Pre-operative (5 repeated measurements over 2 months), post-operative at 2 weeks, 3 months, 6 months, 12 months, and 24 months | 
| Dorsal sensation as assessed by the Graded Redefined Assessment of Strength, Sensibility, and Prehension (GRASSP) dorsal sensation subscale | The GRASSP is a measure of upper extremity strength, sensation, and grip that is specific to patients with tetraplegia. It consists of 5 subscales for each upper extremity: strength (manual muscle testing of 10 muscles in right and left arms - subscale total score encompasses all 10 muscles), dorsal sensation, palmar sensation (measured with Semmes-Weinstein monofilaments), qualitative grasp, and quantitative grasp. Total score (which includes all subscale scores) ranges from 0 to 116 for each upper extremity (right or left arm). The dorsal sensation subscale total score ranges from 0 to 12. The GRASSP will be administered by the nurses or physical therapist involved in the study. | Pre-operative (5 repeated measurements over 2 months), post-operative at 2 weeks, 3 months, 6 months, 12 months, and 24 months | 
| Palmar sensation as assessed by the Graded Redefined Assessment of Strength, Sensibility, and Prehension (GRASSP) palmar sensation subscale | The GRASSP is a measure of upper extremity strength, sensation, and grip that is specific to patients with tetraplegia. It consists of 5 subscales for each upper extremity: strength (manual muscle testing of 10 muscles in right and left arms - subscale total score encompasses all 10 muscles), dorsal sensation, palmar sensation (measured with Semmes-Weinstein monofilaments), qualitative grasp, and quantitative grasp. Total score (which includes all subscale scores) ranges from 0 to 116 for each upper extremity (right or left arm). The palmar sensation subscale total score ranges from 0 to 12. The GRASSP will be administered by the nurses or physical therapist involved in the study. | Pre-operative (5 repeated measurements over 2 months), post-operative at 2 weeks, 3 months, 6 months, 12 months, and 24 months | 
| Qualitative grasp as assessed by the Graded Redefined Assessment of Strength, Sensibility, and Prehension (GRASSP) qualitative grasp subscale | The GRASSP is a measure of upper extremity strength, sensation, and grip that is specific to patients with tetraplegia. It consists of 5 subscales for each upper extremity: strength (manual muscle testing of 10 muscles in right and left arms - subscale total score encompasses all 10 muscles), dorsal sensation, palmar sensation (measured with Semmes-Weinstein monofilaments), qualitative grasp, and quantitative grasp. Total score (which includes all subscale scores) ranges from 0 to 116 for each upper extremity (right or left arm). The qualitative grasp subscale total score ranges from 0 to 12. The GRASSP will be administered by the nurses or physical therapist involved in the study. | Pre-operative (5 repeated measurements over 2 months), post-operative at 2 weeks, 3 months, 6 months, 12 months, and 24 months | 
| Quantitative grasp as assessed by the Graded Redefined Assessment of Strength, Sensibility, and Prehension (GRASSP) quantitative grasp subscale | The GRASSP is a measure of upper extremity strength, sensation, and grip that is specific to patients with tetraplegia. It consists of 5 subscales for each upper extremity: strength (manual muscle testing of 10 muscles in right and left arms - subscale total score encompasses all 10 muscles), dorsal sensation, palmar sensation (measured with Semmes-Weinstein monofilaments), qualitative grasp, and quantitative grasp. Total score (which includes all subscale scores) ranges from 0 to 116 for each upper extremity (right or left arm). The quantitative grasp subscale total score ranges from 0 to 30. The GRASSP will be administered by the nurses or physical therapist involved in the study. | Pre-operative (5 repeated measurements over 2 months), post-operative at 2 weeks, 3 months, 6 months, 12 months, and 24 months | 
| Total Score on the Graded Redefined Assessment of Strength, Sensibility, and Prehension (GRASSP) scale | The GRASSP is a measure of upper extremity strength, sensation, and grip that is specific to patients with tetraplegia. It consists of 5 subscales for each upper extremity: strength (manual muscle testing of 10 muscles in right and left arms - subscale total score encompasses all 10 muscles), dorsal sensation, palmar sensation (measured with Semmes-Weinstein monofilaments), qualitative grasp, and quantitative grasp. Total score (which includes all subscale scores) ranges from 0 to 116 for each upper extremity (right or left arm). The GRASSP will be administered by the nurses or physical therapist involved in the study. | Pre-operative (5 repeated measurements over 2 months), post-operative at 2 weeks, 3 months, 6 months, 12 months, and 24 months | 
| Function (self-care) as assessed by the Spinal Cord Independence Measure III Self Report (SCIM III SR) questionnaire | The SCIM III SR is a measure of independence with activities across 3 subscales: self-care, respiration and sphincter management, and mobility. The self-care subscale ranges from 0 to 20. | Pre-operative (5 repeated measurements over 2 months), post-operative at 2 weeks, 3 months, 6 months, 12 months, and 24 months | 
| Function (respiration and sphincter management) as assessed by the Spinal Cord Independence Measure III Self Report (SCIM III SR) questionnaire | The SCIM III SR is a measure of independence with activities across 3 subscales: self-care, respiration and sphincter management, and mobility. The respiration and sphincter management subscale ranges from 0 to 40. | Pre-operative (5 repeated measurements over 2 months), post-operative at 2 weeks, 3 months, 6 months, 12 months, and 24 months | 
| Function (mobility) as assessed by the Spinal Cord Independence Measure III Self Report (SCIM III SR) questionnaire | The SCIM III SR is a measure of independence with activities across 3 subscales: self-care, respiration and sphincter management, and mobility. The mobility subscale ranges from 0 to 40. | Pre-operative (5 repeated measurements over 2 months), post-operative at 2 weeks, 3 months, 6 months, 12 months, and 24 months | 
| Function as assessed total score on the Spinal Cord Independence Measure III Self Report (SCIM III SR) questionnaire | The SCIM III SR is a measure of independence with activities across 3 subscales: self-care, respiration and sphincter management, and mobility. Total score ranges from 0 to 100( that is, the total score is the sum of scores on the three subscales). | Pre-operative (5 repeated measurements over 2 months), post-operative at 2 weeks, 3 months, 6 months, 12 months, and 24 months | 
| Hand function as assessed by the Michigan Hand Questionnaire (MHQ) total score | The MHQ instrument is a 37 core questions, self-report questionnaire used to assess changes in hand function. The MHQ requires subjects to rate their overall hand function, activities of daily living (ADLs), pain, work performance, aesthetics, and patient satisfaction with hand function. Scores on each of the 6 subscales range from 0 to 100, and an overall MHQ score is calculated by averaging the scores of the 6 subscales. The MHQ will be administered by the physicians or nurses involved in the study. | Pre-operative, post-operative at 2 weeks, 3 months, 6 months, 12 months, and 24 months | 
| Hand function as assessed by the Sollerman Hand Function Test total score | The Sollerman Hand Function Test is a standardized performance test designed to measure handgrips needed for certain activities of daily living (ADLs), such as eating, driving, personal hygiene, and writing. It includes multiple subtests that represent common handgrips and activities, completed using the hands both bilaterally and separately. Scoring of each subtest takes into account the time taken to complete the task, level of difficulty displayed, and quality of performance using correct grips. Scores range from 0 (task cannot be completed) - 4; a total score (0 - 80) is obtained from the sum of scores of all subtests. | Pre-operative, post-operative at 2 weeks, 3 months, 6 months, 12 months, and 24 months | 
| Disability as assessed by the Disabilities of the Arm, Shoulder, and Hand (DASH) instrument total score | The DASH instrument is a 30-item, self-report questionnaire used to assess overall upper extremity function. The DASH requires subjects to rate their ability to perform tasks using the upper extremities. Individuals are instructed to report their ability to perform the tasks, regardless of which arm they use or what strategies they employ. A single disability/symptom score is produced. Scores range from 0-100, where a greater score indicates greater disability. The DASH will be administered by the physicians, nurses, or physical therapist involved in the study. | Pre-operative, post-operative at 2 weeks, 3 months, 6 months, 12 months, and 24 months | 
| Health-related Quality of Life as assessed by the Short Form 36 (SF-36) questionnaire total score | The SF-36 is a questionnaire designed to measure general health and quality of life across eight, scaled scores (vitality, physical functioning, bodily pain, general health perceptions, physical role functioning, emotional role functioning, social role functioning, and mental health)--a total score will be reported. The eight subscales are each given scores, which are the weighted sums of the questions in each subscale section, and each subscale score is directly transformed into a total score of 0-100 scale. The lower the score the more disability,a and the higher the score the less disability (that is, a score of zero is equivalent to maximum disability, and a score of 100 is equivalent to no disability). The SF-36 will be administered by the physicians, nurses, or physical therapist involved in the study. | Pre-operative, post-operative at 2 weeks, 3 months, 6 months, 12 months, and 24 months | 
| Number of participants with intraoperative complications |  | 24 months | 
| Number of participants with post-operative complications |  | 24 months | 
| Number of participants who require reoperation |  | 24 months | 
| Number of participants who receive the nerve transfer intervention soon after their spinal cord injury | The nerve transfer intervention will be considered soon or early if it is less than 12 months after the spinal cord injury that the nerve transfer intervention is intended to treat. This will be assessed at the time of the nerve transfer intervention. | at the time of the nerve transfer intervention | 
| Number of participants with an improvement in hand function as determined by qualitative video analysis |  | Pre-operative, post-operative at 6, 12, and 24 months |