Nerve Transfer Surgery to Restore Upper-limb Function After Cervical Spinal Cord Injury

University of British Columbia

Status: Enrolling

Conditions: Upper Extremity Paralysis; Tetraplegia; Upper Extremity Paresis; SCI - Spinal Cord Injury; Upper Extremity Dysfunction; Cervical Spinal Cord Injury; Spinal Cord Injury at C5-C7 Level; Spinal Cord Injury

Study type: Observational

Funder types: Other

Identifiers

NCT05638191

H20-03350

Details and patient eligibility

About

The goal of this prospective, open label cohort study is to assess functional and motor outcomes in individuals with cervical spinal cord injury who have undergone nerve transfer surgery, with the goal of increasing upper limb function. We will also compare these outcomes to a cohort of similarly matched individuals who have not undergone nerve transfer surgery, using robust outcome measures, rigorous pre-operative clinical and neurophysiological assessments, and standardized rehabilitation. At the end of this project we aim to develop a model for predicting nerve transfer outcomes using pre-operative clinical and neurophysiological characteristics.

Full description

The purposes of this study are:

1. To quantify functional and motor outcomes of NT in patients with SCI, using robust outcome measures, rigorous pre-operative clinical and neurophysiological assessments, and standardized rehabilitation, and to compare these outcomes against individuals who did not undergo nerve transfer surgery.
2. To develop a model for predicting NT outcomes using pre-operative clinical and neurophysiological characteristics.

Outcome measures:

Purpose 1: The primary study outcome is the Graded Redefined Assessment of Strength, Sensibility and Prehension (GRASSP Ver. 1). Secondary outcomes are the Spinal Cord Independence Measure (SCIM) and motor outcomes in recipient muscles following NT, including muscle strength and neurophysiological assessments at 3 months intervals post-operatively, to final outcome measurement at 24 months.

Purpose 2: Relevant demographic, clinical variables and neurophysiological variables (including joint range of motion, muscle spasticity, pain, depression motor unit number estimation in recipient muscles and ultrasound evaluation of recipient muscle quality), are a priori variables that will be collected at baseline, in order to develop a clinical prediction tool to inform prognosis.

Research Design:

All SCI individuals referred to an interdisciplinary clinic for potential nerve transfer will undergo a standardized clinical examination, according to the International Standards for Neurological Classification of Spinal Cord Injury (ISNCSCI), to classify neurological level of injury. As well, electrodiagnostic test which will be performed by one of our highly qualified physicians. Individuals who are deemed candidates for nerve transfer surgery will be screened and invited to participate in the study. Participation in the study will not, in any way, influence clinical care.

After receiving written consent, outcome measurement will take place pre-operatively, then at 3-month intervals post operatively; final analysis will occur at 24 months after surgery. As well, a control group consisting of those SCI individuals who chose to not undergo or are not candidates for surgery will be recruited. This "control group" will undergo assessments at 24 months following their injuries, in line with the anticipated functional plateau in spontaneous recovery expected . Outcome measurement will be performed at GF Strong Rehabilitation Hospital (Primary site), the International Collaboration on Repair Discoveries (ICORD), Sunnybrook Hospital in Toronto, and Kingston Health Science Centre. Rehabilitation will be administered by highly qualified hand therapists with standardized frequency, and duration for all individuals. All study data will be stored in a REDCap database which will be shared between all participating institutions.

Outcome measurement & information collected include:

Graded Redefined Assessment of Strength, Sensibility and Prehension (GRASSP), which is a validated upper limb functional measure, specifically designed for use in SCI (Kalsi-Ryan et al. 2012). It incorporates three domains vital to upper limb function: sensation, strength, and prehension. It is a multimodal test comprising 5 subtests for each upper limb: dorsal sensation, palmar sensation, strength, prehension ability and prehension performance. The GRASSP results in 5 numerical scores that provide a comprehensive profile of upper-limb function and will be administered by GRASSP certified research personnel. As well, individuals will be asked to complete the Spinal Cord Independence Measure (SCIM) questionnaire (Catz A, et al. 1997) on the same day of their visit.

At Baseline, a validated technique called motor unit number estimation (MUNE) counts the number of MN's and can be essential in evaluating MN health. We aim to carry out this technique towards measuring the health of MN's in functionally relevant muscles in patients with SCI and comparing this with healthy controls. The purpose of this study is to provide a quantitative measure of the size of MN pool in clinically relevant muscles below the level of SCI using MPS and MScan MUNE. We will also supplement information about MNs with ultrasound-derived measures of muscle quality.

Ultrasound sonography recording will be taken to analyze the structural health of recipient muscles and to quantify muscle fibrosis and atrophy. The muscles of interest will be anatomically identified and marked, and ultrasound gel will be applied to skin surface of the upper limb prior to placing the ultrasound probe. Individuals will be asked to lie in a dimly lit room for this portion of the study.

Demographic information will be collected for each participant, including

• age;
• sex;
• medical comorbidities; and
• medications

Clinical factors influencing functional and motor recovery in SCI will be measured:

• spasticity with modified Ashworth scores;
• depression with Beck's depression inventory (Beck, A. T., et al. 1996);
• passive ranges of motion in joints targeted by NT; and
• brief pain inventory (Ullrich PM, et al. 2008).

Enrollment: 60 estimated patients

Sex: All

Ages: 18 to 70 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Motor complete (AIS A or B) between neurological level of injury C5 and C8
• Able to provide informed written consent
• Able to attend and comply with the testing protocols
• Able to understand and speak English or have access to an appropriate interpreter as judged by the investigator.

Exclusion criteria

• An uncontrolled medical condition (e.g. uncontrolled cardiovascular disease, diabetes, kidney or liver disease)
• Have ever received botulinum toxin injections (Botox) for tone management in the upper limb
• An unmanaged secondary complication of SCI including but not limited to uncontrolled neuropathic pain or spasticity, syringomyelia, fracture, urinary tract infection or significant pressure ulcer, preventing participation in testing

Trial design

60 participants in 2 patient groups

Experiemental: Surgical Arm

Description:

Individuals in this group will receive nerve transfer surgery 6 - 9 months post cervical spine injury and be observed for two years post-operatively.

Control: Non-surgical

Description:

Individuals in this group will not have undergone nerve transfer surgery. They will be observed for two years post injury while receiving standard of care including medical and rehabilitation. We want to reinforce that individuals are not being randomized to surgery versus non-surgery. Rather individuals this group will either have made the decision not to undergo surgery, independent their participation in this study.