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

The goal of this prospective, open-label cohort study is to assess functional outcomes in individuals with cervical spinal cord injury who have undergone nerve transfer surgery to restore upper limb function. The main questions it aims to answer are:

• Does nerve transfer improve hand function in individuals with cervical spinal cord injury?
• What factors are associated with functional improvement following nerve transfer? Researchers will compare functional outcomes at 24 months post-surgery to 1) baseline outcomes and 2) individuals with cervical spinal cord injury who did not undergo nerve transfer.

Participants who have received nerve transfer surgery as part of their regular medical care will complete functional hand tests, electrodiagnostic assessments, and questionnaires on independence and mood every 3 months for 24 months after surgery.

Study Overview

• Status: Recruiting
• Conditions: Upper Extremity Dysfunction; Cervical Spinal Cord Injury; Spinal Cord Injury; Spinal Cord Injury at C5-C7 Level; SCI - Spinal Cord Injury; Upper Extremity Paralysis; Tetraplegia; Upper Extremity Paresis
• Intervention / Treatment: Procedure: Nerve transfer surgery

Detailed Description

All individuals with spinal cord injury (SCI) referred to an interdisciplinary clinic for potential nerve transfer undergo a standardized clinical examination, according to the International Standards for Neurological Classification of Spinal Cord Injury (ISNCSCI), to classify the neurological level of injury. Additionally, individuals receive detailed sensorimotor and electrodiagnostic evaluations, and their upper-limb goals are carefully explored. They are then monitored for spontaneous upper limb motor recovery over the next 2.5-3 months, at which point they are re-evaluated with electrodiagnostic testing. 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 (approximately 5-6 after injury) and at 3-month intervals post-operatively through 24 months after surgery. Primary and secondary outcomes are measured for each limb undergoing nerve transfer, so participants can be included in the study even if they receive double nerve transfer on only one limb. Outcome measurement will be performed at GF Strong Rehabilitation Hospital (Primary site; Vancouver), the International Collaboration on Repair Discoveries (ICORD; Vancouver), Sunnybrook Hospital (Toronto), Kingston Health Science Centre (Kingston), and Dalhousie University (Halifax). All study data will be stored in a REDCap database, which will be shared between all participating institutions. We will carefully document any adverse events during the peri-operative and post-operative rehabilitation phases. Adverse events will be classified according to the CTCAE Grading System.

Study outcomes in the surgical (experimental) group will be compared with those of a historical control group derived from a multicenter cohort study (PMID: 35652348). Participants in the surgical cohort will be matched 1:1 with historical controls based on age, sex, and injury characteristics. Given the invasiveness of the intervention, randomization and blinding are not possible. Therefore, our team used a non-blinded, non-randomized design - features that reduce the level of evidence provided by the data. Every attempt has been made to minimize bias, including using an objectively measured primary outcome and adding a control group to facilitate comparison to those without nerve transfer. There are biases and potential confounding effects of using historical controls, including differences in measurement techniques and sociocultural and health system factors.

A linear mixed-effects model will be used to determine whether nerve transfer improves functional hand outcomes from baseline to 24 months post-surgery. Analyses will be conducted at the limb level, with fixed effects for time (baseline, 24 months) and a random intercept for participant to account for any correlation between limbs contributed by the same participant. To quantify the within-participant improvement in our primary outcome, the adjusted mean change in the surgical group from pre-operative to 24 months post-surgery will be estimated. We will also compare the mean change in GRASSP in the surgical group to the change in GRASSP of the historical control cohort between 6 and 12 months post-injury. We believe this comparison is justified as individuals with motor complete injuries reach neurological stability around 1 year post-injury. 95% confidence intervals and two-sided p-values will be reported for both analyses (α = 0.05).

We will also perform an exploratory analysis to identify baseline factors associated with upper-limb function at 24 months after nerve transfer surgery. This analysis will be restricted to the surgical cohort and will use the 24-month GRASSP score as the outcome. Prespecified predictors include participant age, neurological level of injury, and baseline donor nerve health. Donor nerve health will be summarized as the number of donor nerves demonstrating PSA on baseline needle EMG (range 0-2 per limb). These analyses are intended to identify candidate predictors to inform future multivariable clinical prediction model development.

The trial is powered based on the within-participant change in total GRASSP from the pre-operative baseline to 24 months post-surgery (two-sided α = 0.05). Because no paired data are available for this interval on the total GRASSP score, we based the calculation on external data from the GRASSP version II sensation subtest, which reported a paired effect size d = 0.69 on motor-complete SCI patients from baseline (~10 days post-injury) to 12 months post-injury (PMID: 31573454). Under these assumptions, the required number of participants with 24-month post-injury data to achieve 95% power is 29 (calculated using the pwr R package); assuming a 90% retention rate, the recruitment target increases to 33 participants. To account for the possibility that total GRASSP may be more variable than the sensation subtest, we inflated the target by 20%, resulting in a planned sample of 40 participants. Power was calculated at the participant level, allowing for the inclusion of up to 80 surgical limbs.

• Study Type: Observational
• Enrollment (Estimated): 40

Contacts and Locations

• Study Contact: Name: Michael Berger, MD, PhD; Phone Number: 778-990-7615; Email: michael.berger@vch.ca

Study Locations

• Canada
  • British Columbia
    • Vancouver, British Columbia, Canada, V5Z 2G9
      • Recruiting
      • GF Strong Rehabilitation Hospital
      • Contact: Harvey Wu, MD; Email: harvey.wu@ubc.ca
      • Principal Investigator: Michael Berger, MD, PhD
      • Sub-Investigator: Russell O'Connor, MD
      • Sub-Investigator: Erin Brown, MD
      • Sub-Investigator: Chris Doherty, MD
      • Sub-Investigator: Amy Hanlan, MD
  • Nova Scotia
    • Halifax, Nova Scotia, Canada, B3H 3A7
      • Recruiting
      • QEII Health Sciences Centre
      • Contact: Emily Krauss
      • Principal Investigator: Emily Krauss, MD, MSc
  • Ontario
    • Kingston, Ontario, Canada, K7L 5G2
      • Recruiting
      • Kingston Health Sciences Centre
      • Contact: Michael Hendry, MD, MSc
      • Principal Investigator: Michael Hendry, MD, MSc
    • Toronto, Ontario, Canada, M4N 3M5
      • Recruiting
      • Sunnybrook Health Sciences Centre
      • Contact: Jana Dengler, MD, MASc
      • Principal Investigator: Jana Dengler, MD, MASc

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• 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.

Description

Inclusion Criteria:

• Traumatic, motor-complete cervical SCI (AIS A or B)
• Male or female, ages 18-70
• Consent and plan to undergo nerve transfer to restore grasp function in at least one limb
• Motor grade 4-5 at C5
• Motor grade 0-1 at C8/T1
• Injury duration within 6 months at the time of surgery
• English-speaking and cognitively intact
• Able to provide informed written consent
• Able to attend and comply with the testing protocols

Exclusion Criteria:

• Inability or unwillingness to participate in post-operative rehabilitation (in person or virtual)
• Secondary complication of SCI (e.g., intractable neuropathic pain, edema, contracture) or major medical comorbidity (e.g., traumatic brain injury) that would independently influence response to surgery or ability to participate in rehabilitation

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Experimental: Surgical Arm; Individuals in this group will receive nerve transfer surgery 6 - 9 months post cervical spine injury and be observed for two years post-operatively.	Procedure: Nerve transfer surgery; The intervention in this study, which follows our clinical approach, is the "double nerve transfer" to restore grasp function (i.e., hand opening and hand closing). Finger and thumb extension (hand opening) is restored via the supinator-posterior interosseous nerve (PIN) transfer. Finger and thumb flexion (hand closing) is restored via a nerve transfer to the anterior interosseous nerve (AIN). There are two donor nerve options available to restore function to the muscles supplied by the AIN: the nerve to the brachialis and the nerve to the extensor carpi radialis longus (ECRL) or extensor carpi radialis brevis (ECRB).
Control: Non-surgical; Historical control data will be drawn from a published multi-center longitudinal trial that assessed outcomes in individuals with acute traumatic cervical SCI within ten days of injury (baseline), and again at one, three, six, and 12 months post-injury (PMID: 35652348). The general inclusion criteria for this study was traumatic tetraplegia, at least 1/5 strength in the C5 myotome, age 16 years or older, and the ability to provide informed consent. Exclusion criteria included brain injury or other neurological impairments affecting upper limb function. Participants in the surgical cohort will be matched 1:1 with historical controls based on age, sex, and injury characteristics (i.e., NLI and AIS grade).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
GRASSP (within-participant)	Change in Graded Redefined Assessment of Strength, Sensibility and Prehension (GRASSP) score from baseline to 24 months post-surgery. GRASSP is a validated upper limb functional measure and previously is used in SCI (Kalsi-Ryan et al. 2012) incorporates three domains vital to upper limb function: sensation, strength, and prehension.	Baseline then every 3 months for 2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
GRASSP (between-participant)	Difference in longitudinal change in mean total GRASSP score between the surgical cohort and matched historical controls with cervical SCI who did not receive nerve transfer	From enrollment to the study endpoint

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Modified Ashworth scores (MAS)	Modified Ashworth Scale (MAS) have been utilized in spinal cord injury patient population to assess spasticity by examining muscle tones.	Baseline then every 3 months for 2 years
Range of Motion	A Goniometer is used to measure range of motion of the joint angles (degrees) from the axis of the joint. The measurement of joint movements is compared to its full potential.	Baseline then every 3 months for 2 years
Douleur Neuropathique 4 (DN-4)	A questionnaire consisting of 10 items and can be useful in assessment of neuropathic pain. The items related to pain quality are based on an interview and examination of the patient.	Baseline then every 3 months for 2 years
Beck's Depression Inventory (BDI)	The questionnaire is a 21-item, self-report rating inventory that measures characteristic attitudes and symptoms of depression.	Baseline then every 3 months for 2 years
Donor nerve health	The presence (or absence) of pathological spontaneous activity will be determined in donor muscles using needle electromyography.	Baseline
Spinal Cord Independence Measure Version III (SCIM-III)	The SCIM-III has been developed to address three specific areas of function in patients with spinal cord injuries such as activities of daily living, respiration and sphincter management, and a patient's mobility abilities.	Baseline then every 3 months for 2 years

Collaborators and Investigators

• Sponsor: University of British Columbia
• Collaborators: University of Toronto; Queen's University; Dalhousie University; Wings for Life
• Investigators: Principal Investigator: Michael Berger, MD, PHD, University of British Columbia

Study record dates

Study Major Dates

• Study Start (Actual): June 3, 2021
• Primary Completion (Estimated): January 1, 2028
• Study Completion (Estimated): January 1, 2028

Study Registration Dates

• First Submitted: November 1, 2022
• First Submitted That Met QC Criteria: December 1, 2022
• First Posted (Actual): December 6, 2022

Study Record Updates

• Last Update Posted (Actual): May 29, 2026
• Last Update Submitted That Met QC Criteria: May 27, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: spinal cord injury; upper extremity nerve transfer; nerve transfer; SCI; nerve reconstruction; quadriplegia; paresis
• Additional Relevant MeSH Terms: Neurologic Manifestations; Central Nervous System Diseases; Nervous System Diseases; Wounds and Injuries; Trauma, Nervous System; Spinal Cord Diseases; Paralysis; Pathological Conditions, Signs and Symptoms; Signs and Symptoms; Paresis; Spinal Cord Injuries; Quadriplegia
• Other Study ID Numbers: H20-03350

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED
• IPD Plan Description: The IPD sharing plan is under discussion.

Drug and device information, study documents

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