Clinical trial NCT05638191: Nerve Transfer Surgery to Restore Upper-limb Function After Cervical Spinal Cord Injury
Official title: Nerve Transfer Surgery to Restore Upper-limb Function After Ceervical Spinal Cord Injury
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Spinal Cord Injury
Spinal Cord Injury at C5-C7 Level
SCI - Spinal Cord Injury
Upper Extremity Paralysis
Upper Extremity Dysfunction
Tetraplegia
Upper Extremity Paresis
Cervical Spinal Cord Injury
Keywords: spinal cord injury
upper extremity nerve transfer
nerve transfer
SCI
nerve reconstruction
quadriplegia
paresis
Lead sponsor: University of British Columbia
Sponsor class: OTHER
Collaborators: name: Queen's University
name: Dalhousie University
name: University of Toronto
name: Wings for Life
First posted: 2022-12-06
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patient referrals are ensured through established care pathways for upper-limb rehabilitation in SCI, including nerve transfer. Research objectives will be facilitated through already available institutional clinical and rehabilitation resources at each study site. Potential participants will be informed of the study directly by their treating physicians. The research study will be introduced by the PI or one of the co-Is of the study, who are also responsible for clinical care of all prospective participants.

Brief summary: 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.

Detailed 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).

Eligibility criteria: 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

Primary outcomes:
measure: Graded Redefined Assessment of Strength, Sensibility and Prehension (GRASSP)
timeFrame: Baseline then every 3 months for 2 years
Secondary outcomes:
measure: Modified Ashworth scores (MAS)
timeFrame: Baseline then every 3 months for 2 years
measure: Range of Motion
timeFrame: Baseline then every 3 months for 2 years
measure: Ultrasound
timeFrame: Baseline then every 3 months for 2 years
measure: Spinal Cord Independence Measure (SCIM)
timeFrame: Baseline then every 3 months for 2 years
measure: Douleur Neuropathique 4 (DN-4)
timeFrame: Baseline then every 3 months for 2 years
measure: Beck's Depression Inventory (BDI)
timeFrame: Baseline then every 3 months for 2 years
Other outcomes:
Locations:
city: Vancouver
country: Canada
facility: GF Strong Rehabilitation Hospital
state: British Columbia
city: Halifax
country: Canada
facility: QEII Health Sciences Centre
state: Nova Scotia
city: Kingston
country: Canada
facility: Kingston Health Sciences Centre
state: Ontario
city: Toronto
country: Canada
facility: Sunnybrook Health Sciences Centre
state: Ontario
Study officials:
affiliation: University of British Columbia
name: Michael Berger, MD, PHD
role: PRINCIPAL_INVESTIGATOR
References: