Nerve Transfer After Spinal Cord Injury- Multi-center

Nerve Transfers to Improve Upper Extremity Function and Quality of Life in Tetraplegic Patients

Current treatment strategies of acute cervical spinal cord injuries remain limited. Treatment options that provide meaningful improvements in patient quality of like and long-term functional independence will provide a significant public health impact. Specific aim: Measure the efficacy of nerve transfer surgery in the treatment of patients with complete spinal cord injuries with no hand function. Optimize the efficiency of nerve transfer surgery by evaluating patient outcomes in relation to patient selection and quality of life and functional independence.

Study Overview

• Status: Recruiting
• Conditions: Spinal Cord Injuries; Tetraplegia; Quadriplegia Flaccid
• Intervention / Treatment: Procedure: Surgery/Occupational Therapy

Detailed Description

Study Design and Feasibility: A prospective multi-institutional non-randomized single arm design will be utilized. Seventy subjects with cervical ASIA A-B (International Standards for Neurological Classification of Spinal Cord Injury) SCI and hand function impairment that fit the International Classification for Surgery of the Hand 0-4 will be identified. Only patients with stable ASIA scores and no evidence of functional improvement in motor or sensory examination for at least 3 months will be recruited. All patients will undergo Electromyography (EMG) and nerve conduction studies (NCS) to verify intact innervation (normal compound muscle action potentials (CMAPs)) to the paralyzed target muscles below the level of injury. Functional electrical stimulation (FES) will be used to verify loss of lower motor neuron function in key muscle groups in the zone of injury and help differentiate those muscle with intact connections to preserve anterior horn cells. Only those patients with clinically normal, Medical Research Council (MRC) muscle grade 5/5 donor (axonal donor) function will be enrolled.

Outcome Measures Primary Outcome Measures: Pre- and Post-operative upper motor strength. (Manual motor testing & Hand Held Dynamometry) Secondary Outcome Measures: Disabilities of the Arm, Shoulder, and Hand (DASH), Michigan Hand Questionnaire (MHQ), Spinal Cord Injury Quality of Life (SCIQOL), GRASSP test (pre-operative, post-operatively - 6 months, 12 months, and 24 months, 36 months and 48 months), rates of intraoperative and post-operative complications, and rates of reoperation.

Rehabilitation and hand therapy are critical components of motor re-education following nerve transfers. Cortical plasticity and motor remapping occurs following nerve transfers allowing independent functional control of the recipient muscles. All patients will begin rehabilitation and hand therapy beginning 2 weeks after surgery. They undergo one hour of hand therapy and occupational therapy for motor re-education once to twice a week for 48 months following surgery. Rehabilitation will be phased to early and late - added exercises focusing on co-contraction, repetition, and range of motion will be included as home therapy.

• Study Type: Observational
• Enrollment (Estimated): 70

Contacts and Locations

• Study Contact: Name: Linda A Koester, BS; Phone Number: 314-362-7368; Email: koesterl@wustl.edu

Study Locations

• Canada
  • Alberta
    • Calgary, Alberta, Canada, T2N 2T9
      • Recruiting
      • Alberta Health Services - Foothills Medical Center
      • Contact: Ish Bains; Phone Number: 403-944-4334; Email: Ish.Bains@albertahealthservices.ca
      • Principal Investigator: Rajiv Midha, MD
    • Edmonton, Alberta, Canada, T6G 2E1
      • Not yet recruiting
      • University of Alberta
      • Contact: Mithun Rajshekar, PhD; Email: rajsheka@ualberta.ca
      • Principal Investigator: Andrew Jack, MD
• United States
  • California
    • Stanford, California, United States, 94305
      • Recruiting
      • Stanford University
      • Contact: Anthony Bet, BS; Phone Number: 650-683-5823; Email: abet0915@stanford.edu
      • Contact: Thomas Wilson, MD; Email: wilsontj@stanford.edu
      • Principal Investigator: Thomas J Wilson, MD
  • Florida
    • Miami, Florida, United States, 33136
      • Recruiting
      • University of Miami
      • Contact: George Jimsheleishvili, MD; Phone Number: 305-243-4781; Email: gxi150@med.miami.edu
      • Contact: Patricia Graham, MS; Phone Number: 305-243-5119; Email: pgraham1@med.miami.edu
      • Principal Investigator: Stephen S Burks, MD
      • Sub-Investigator: Allan D. Levi, MD
  • Maryland
    • Baltimore, Maryland, United States, 21287
      • Recruiting
      • Johns Hopkins University
      • Contact: Aston King; Phone Number: 667-306-8862; Email: aking64@jhu.edu
      • Principal Investigator: Sami Tuffaha, MD
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • Recruiting
      • University of Michigan
      • Principal Investigator: Yamaan Saadeh, MD
      • Contact: Savannah Solomon; Phone Number: 734-936-7010; Email: ssavanna@med.umich.edu
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Recruiting
      • Washington University
      • Contact: Linda Koester, BS; Phone Number: 314-362-7368; Email: koesterl@wustl.edu
      • Sub-Investigator: Neringa Juknis, MD
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Recruiting
      • University of Pennsylvania
      • Contact: Leah Coghlan, BSN; Phone Number: 215-615-5436; Email: ncrdneuroicu@uphs.upenn.edu
      • Principal Investigator: Eric Zager, MD
      • Contact: Lora Assi; Phone Number: 215-595-4584; Email: lora.assi@pennmedicine.upenn.edu
  • Texas
    • Houston, Texas, United States, 77030
      • Recruiting
      • Houston Methodist
      • Contact: Amber Behne, CCRP; Phone Number: 346-238-6424; Email: abehne@houstonmethodist.org
      • Contact: Rachel Markley, MPH; Phone Number: 713-441-3770; Email: rmarkley@houstonmethodist.org
      • Principal Investigator: Amir Faraji, MD
    • Houston, Texas, United States, 77030
      • Terminated
      • The University of Texas Houston Health Science Center
  • Utah
    • Salt Lake City, Utah, United States, 84132
      • Recruiting
      • University of Utah
      • Contact: Kirstianna Lombardi, BA/MA; Phone Number: 801-585-9821; Email: u6039943@utah.edu
      • Contact: Mark Mahan, MD; Email: mark.mahan@hsc.utah.edu
      • Principal Investigator: Mark Mahan, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Participants with a traumatic cervical spine injury with little to no use of his/her arms/hands.

Description

Inclusion Criteria

1. Age 18-65, inclusive
2. At least 3 months of non-operative rehab therapy
3. Mentally and physically willing and able to comply with evaluations
4. Less than 36 months post-injury
5. Stable ASIA scores with no evidence of functional improvement in motor or sensory examination for at least 3 months
6. ASIA A or B determined by the International Standards for Neurological Classification of Spinal Cord Injury (ISNCSCI)
7. EMG/NCS verifies intact innervation (normal CMAPs) to the paralyzed target muscles below the level of injury
8. Functional electrical stimulation (FES) will be performed. Subject must have clinically normal MRC grade 5/5 donor (axonal) function
9. Injury Level C4-C8

Exclusion Criteria

1. Active infection at the operative site or systemic infection
2. Any return or ongoing clinical recovery of distal motor function
3. Mentally or physically compromised that will prevent them from complying with evaluations.
4. Immunologically suppressed
5. Currently undergoing long-term steroid therapy
6. Active malignancy
7. Pregnant
8. Significant joint contractures and/or limitations in passive range of motion in the arm or hand, per treating surgeon's discretion
9. Lack of appropriate social support and/or infrastructure to commit to scheduled follow-up visits.
10. Patients who are planning on undergoing a tendon transfer during the study period or who have had a tendon transfer in the past.

Study Plan

How is the study designed?

Design Details

• Observational Models: Case-Only
• Time Perspectives: Prospective

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Surgery; Surgery/ Occupational Therapy	Procedure: Surgery/Occupational Therapy; Surgery based on function and injury/ Occupational therapy for 48 months post-surgery

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Manual Motor Testing	Change from baseline testing strength of upper extremities at 48 months post-operatively	48 months
Handheld Dynamometry	Change from baseline grip strength at 48 months post-operatively	48 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Disabilities of Arm, Shoulder and Hand (DASH) scores	Change from baseline DASH scores at 48 months post-operatively. Scores range from 0-100 with 0 being the most positive score representing no arm, shoulder or hand disability and 100 being the lowest score indicating the most severe arm, shoulder and hand disability.	48 months
Change in Spinal Cord Injury Quality of Life (SCIQOL) scores	Change in baseline SCIQOL scores at 48 months post-operatively. Five scores of 0-30 (0=less satisfied and 30=most satisfied) are calculated: 1. Total Quality of Life; 2. Health and Functioning Subscale; 3. Social and Economic Subscale; 4. Psychological/Spiritual Subscale; 5 Family Subscale. Calculation of scores weighs satisfaction scores according to level of importance assigned to each item. An overall score can be obtained by summing the scores for all six scales after reversing the pain scale and dividing by six.	48 months
Rates of Intra-operative and post-operative complications	The number of complications within and after the operation	48 months
Hand Function, measured by the GRASSP test	Change in baseline GRASSP Test results for hand function at 48 months post-operatively	48 months
Changes in the Graded Redefined Assessment of Strength, Sensation and Prehension scores (GRASSP)	Change in baseline GRASSP results for strength, sensation and prehension at 48 months post-operatively. Five subtests: 1. Dorsal sensation (3 locations) each scored 0-4 (sum =subtest score, 0-12, with 0 being no sensation and 12 being normal sensation); 2. Palmar sensation (same as above); 3. Strength (10 muscles of arms and hand), motor grad 0-5 for each (sum = subtest total 0-50 with 0 being worst score and 50 being full motor function in all muscles); 4. Prehension ability - 3 grasps (cylindrical, lateral key, tip to tip) - each scored 0-4 (sum=subtest score, 0-12 with 0 being worst function and 12 being no dysfunction); 5 Prehension performance - 6 prehension tasks (pour water, open jars, pick up and turn key, transfer 9 pegs from board, pick up four coins and place in slot and screw 4 nuts on bolt - each scored 0-5 (sum=subtest score 0-30 with 0 being worst score to 30 being best possible score.	48 months
Neuro Quality of Life - Depression Short Form (NQOL-Dep)	Changes in baseline NQOL-Dep scores at 48 months post-operatively. Scores range from 8-40 with 8 being best outcome and 40 being the worst outcome	48 months
Neuro Quality of Life - Upper Extremity Short Form (NQOL-UEF)	Changes in baseline NQOL-UEF scores at 48 months post-operatively. Scores range from 8-40 with 40 being the best outcome and 8 being the worst possible outcome.	48 Months

Collaborators and Investigators

• Sponsor: Washington University School of Medicine
• Collaborators: Johns Hopkins University; University of Pennsylvania; University of Miami; United States Department of Defense; University of Michigan; University of Alberta; Stanford University; University of Calgary; University of Utah; The Methodist Hospital Research Institute
• Investigators: Principal Investigator: Wilson Z Ray, MD, Washington University School of Medicine

Publications and helpful links

Helpful Links

• Washington University Neurosurgery Website

Study record dates

Study Major Dates

• Study Start (Actual): April 13, 2020
• Primary Completion (Estimated): March 1, 2026
• Study Completion (Estimated): December 1, 2026

Study Registration Dates

• First Submitted: July 11, 2019
• First Submitted That Met QC Criteria: July 15, 2019
• First Posted (Actual): July 17, 2019

Study Record Updates

• Last Update Posted (Actual): April 2, 2024
• Last Update Submitted That Met QC Criteria: April 1, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: spinal cord injury; nerve transfer; quadriplegia; tetraplegia
• Additional Relevant MeSH Terms: Central Nervous System Diseases; Nervous System Diseases; Neurologic Manifestations; Wounds and Injuries; Trauma, Nervous System; Spinal Cord Diseases; Paralysis; Spinal Cord Injuries; Quadriplegia
• Other Study ID Numbers: SC180063

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: No plan to share individual participant data. Only aggregate data will be published.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No