Clinical trial NCT06541041: Nerve Transfers Plus Electrical Stimulation to Improve Hand Function in Cervical Spinal Cord Injury
Official title: Evaluation of Electrical Stimulation During Nerve Transfer Surgery for Cervical Spinal Cord Injury
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Cervical Spinal Cord Injury
Cervical Spinal Cord Paralysis
Tetraplegia
Tetraplegia/Tetraparesis
Tetraplegic Spinal Paralysis
Keywords: Cervical Spinal Cord Injury
Nerve Transfer
Brief Intraoperative Electrical Stimulation
Peripheral Nerve Stimulation
Tetraplegia
Lead sponsor: Stanford University
Sponsor class: OTHER
Collaborators: name: United States Department of Defense
First posted: 2024-08-07
Enrollment: 10
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: OTHER
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Cervical spinal cord injury patients aged 18-65 years with neurological level of injury C6 or C7 and limited or no hand function

Brief summary: The goal of this prospective observational study is to determine whether brief intraoperative electrical stimulation and temporary postoperative electrical stimulation improve motor and/or pain outcomes for patients with cervical spinal cord injury undergoing standard of care nerve transfer surgery to improve hand function.

The main hypotheses include:

Hypothesis #1: Brief intraoperative electrical stimulation of the donor nerves will result in improved motor outcomes (hand function) compared to standard nerve transfer surgery in patients with cervical spinal cord injuries.

Hypothesis #2: Placement of a temporary peripheral nerve stimulator for 60 days of postoperative electrical stimulation will result in improved pain outcomes compared to standard nerve transfer surgery in patients with cervical spinal cord injuries.

Researchers will prospectively enroll patients with cervical spinal cord injury and no hand function who will undergo standard of care nerve transfer surgery combined with standard of care brief intraoperative electrical stimulation and temporary postoperative electrical stimulation. Motor and pain outcomes will be compared to a retrospective group of patients who underwent nerve transfer surgery without intraoperative or postoperative electrical stimulation.

Participants will receive standard medical care (nothing experimental) as part of this study. Participants will:

* Have a preoperative assessment including physical examination, electrodiagnostic studies, functional electrical stimulation, and will complete questionnaires assessing function and quality of life
* Agree upon a surgical plan, including the specific nerve transfers to be performed and whether to include brief intraoperative electrical stimulation and/or temporary postoperative electrical stimulation before being considered for enrollment in the study
* Will undergo standard of care nerve transfer surgery, with at least one nerve transfer targeting improvement in hand function and will receive brief intraoperative electrical stimulation of the donor nerves and placement of a temporary peripheral nerve stimulator
* Will follow-up with the surgeon 3, 6, 12, 24, and 36 months after the surgery
* Will have a physical examination and will complete questionnaires at the postoperative visits
* Will participate in hand therapy following the operation
* Will be eligible for placement of a permanent peripheral nerve stimulator, depending on response to the temporary peripheral nerve stimulator.

Detailed description: Background:

Spinal cord injury (SCI) is a major problem facing the general public, with particular relevance for military personnel, given the high frequency of SCI in combat-related injuries. Nerve transfer surgery is one option for restoring function in cervical SCI patients that shows great promise. A nerve transfer involves sacrificing a working nerve that arises from a spinal cord segment above the zone of injury and connecting it to a non-working nerve to reinnervate a target muscle. Restoring hand function is consistently rated by SCI patients, including our lived experience consultants, as most important, even more important than walking or bowel/bladder control. Nerve transfer surgery has been shown to be effective in restoring hand function, but additional improvements are needed, especially for restoring grasp. Furthermore, pain is a significant problem in patients with cervical SCI, with an unmet need for options for treating pain in these patients. Peripheral nerve electrical stimulation has been shown to improve axonal regeneration, muscle reinnervation, and motor recovery and has been used to treat neuropathic pain. Thus, the use of peripheral nerve electrical stimulation has the potential to simultaneously improve motor and pain outcomes in cervical SCI patients undergoing nerve transfer surgery but has never been studied.

Objectives/Hypotheses:

The investigators hypothesize that brief intraoperative electrical stimulation of the donor nerves will result in improved motor outcomes compared to standard nerve transfer. We also hypothesize that placement of a temporary peripheral nerve stimulator for 60 days of postoperative electrical stimulation will result in improved pain outcomes compared to standard nerve transfer.

Specific Aim:

Compare motor and pain outcomes for nerve transfers in cervical spinal cord injury patients with and without peripheral nerve stimulation.

Study Design:

A single center, unblinded, single arm, non-randomized, observational design will be utilized. A total of 10 patients with cervical spinal cord injury classified as ASIA A or B, with International Standards for Neurological Classification of Spinal Cord Injury neurological level of injury C6 or C7 will be recruited and will undergo standard end-to-end nerve transfer surgery targeting restoration of finger extension (posterior interosseous nerve recipient) and finger flexion (anterior interosseous nerve recipient) according to standard clinical care. The test intervention will consist of intraoperative brief electrical stimulation of the donor nerves and postoperative electrical stimulation via a temporary, implantable peripheral nerve stimulator. Intraoperative brief electrical stimulation (BES) will be performed using a handheld nerve stimulator to stimulate the donor nerves at 2 mA with a 200 µs pulse duration for 10 minutes. The implantable peripheral nerve stimulator will be programmed to optimize postoperative pain control on an individualized basis. The peripheral nerve stimulator will be explanted after 60 days, as is intended for this device. The primary outcomes will be manual motor testing graded on the Medical Research Council (MRC) scale (0-5) for the extensor digitorum communis (EDC) and flexor pollicis longus (FPL) and the Numeric Rating Scale (NRS) for pain in the treated extremity (0-10). Patients will have a baseline preoperative electrodiagnostic study and functional electrical stimulation performed, with the decision for surgery occurring as part of standard clinical care. Assessments will occur preoperatively and postoperatively at 3, 6, 12, 24, and 36 months. The researchers will compare these data to a retrospective group of patients who underwent similar nerve transfer surgery without intraoperative or postoperative electrical stimulation.

Eligibility criteria: Inclusion Criteria:

1. Cervical spinal cord injury, ASIA A or ASIA B
2. International Standards for Neurological Classification of Spinal Cord Injury neurological level of injury C6 or C7
3. Agreed upon surgical plan includes at least 1 nerve transfer targeting finger flexion with the anterior interosseous nerve as the recipient and at least 1 nerve transfer targeting finger extension with the posterior interosseous nerve as the recipient
4. Age 18-65 years
5. Mentally and physically able to comply with evaluations and assessments
6. Upper motor neuron pattern of injury in the recipient nerve with planned surgery 36 months or less from the time of injury OR lower motor neuron pattern of injury in the recipient nerve with planned surgery 9 months or less from the time of injury
7. Muscle grade at least 4+/5 on the Medical Research Council (MRC) scale in the territory of the donor nerve(s)
8. Stable function for at least 3 months (i.e., no ongoing recovery)
9. Non-operative rehabilitation for at least 3 months
10. Able to read and write in English at a level necessary to complete the questionnaires

Exclusion Criteria:

1. Contraindication to electrical stimulation, including any implanted electronic device such as a pacemaker or intrathecal drug delivery pump
2. Active infection at the operative site or systemic infection
3. Active malignancy
4. Pregnancy
5. Joint contractures or limited passive range of motion that would limit recovery of function
6. Lack of appropriate social support and/or infrastructure to commit to scheduled follow-up visits
7. Previous tendon transfer or other surgery for restoration of function following cervical spinal cord injury
8. Planned tendon transfer surgery or other surgery for restoration of function following cervical spinal cord injury

Primary outcomes:
measure: Composite Motor Score
timeFrame: 36 Months Postoperative
measure: Percentage of Baseline Pain
timeFrame: 6 Months Postoperative
Secondary outcomes:
measure: Manual Motor Testing
timeFrame: 6, 12, and 24 Months Postoperative
measure: Percentage of Baseline Pain
timeFrame: 3 Weeks, 12, 24, and 36 Months Postoperative
measure: DASH Score
timeFrame: 6, 12, 24, and 36 Months Postoperative
measure: MHQ Score
timeFrame: 6, 12, 24, and 36 Months Postoperative
measure: SCIM III Score
timeFrame: 6, 12, 24, and 36 Months Postoperative
measure: Zung SDS
timeFrame: 6, 12, 24, and 36 Months Postoperative
Other outcomes:
Locations:
city: Palo Alto
country: United States
facility: Stanford University/Stanford Health Care
state: California
Study officials:
affiliation: Stanford University
name: Thomas J Wilson, MD, MPH
role: PRINCIPAL_INVESTIGATOR
References: