Nerve Graft Surgery for Spinal Cord Injury

Overseen By Kris P Dyer, MPH, BS

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: University of Kentucky

Disqualifiers: Unconsciousness, ASIA grade C-E, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

Duration: 12 months

10 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests two surgical approaches for treating spinal cord injuries. One group will undergo spinal decompression surgery alone, while the other will receive the same surgery plus a nerve graft. The nerve graft involves adding a piece of nerve from the leg to aid spine repair. The trial aims to determine if the nerve graft enhances the safety and effectiveness of the surgery. Individuals with a recent neck or upper back spinal cord injury who can undergo surgery within 48 hours may be suitable candidates for this trial. As an unphased trial, it offers participants the chance to contribute to groundbreaking research that could improve surgical outcomes for future patients.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that a surgical procedure called dorsal myelotomy and expansive duraplasty (DMED), with or without autologous nerve graft implantation (ANGI), is under careful study for safety. In earlier studies, this surgery showed promise in treating spinal cord injuries. Most patients tolerated the procedure well, but all surgeries carry risks. Some patients might experience discomfort or complications, which are usually monitored closely.

For the nerve graft component, studies have shown that using a person's own nerve tissue is generally safe. This method avoids the need for immune-suppressing drugs, which are often required when using donor tissue. This type of transplant has shown positive results in aiding nerve recovery.

While researchers continue to study the treatment, these findings offer a hopeful outlook for safety. Prospective trial participants should discuss any concerns with their doctor. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the nerve graft surgery for spinal cord injury because it introduces a new approach by combining dorsal myelotomy and expansive duraplasty (DMED) with supplemental autologous nerve graft implantation (ANGI). Unlike traditional spinal decompression techniques, which primarily aim to relieve pressure on the spinal cord, this innovative method actively seeks to repair nerve damage by implanting the patient's own nerve tissue. This approach has the potential to enhance nerve regeneration and improve functional recovery, offering hope for more effective treatment outcomes in spinal cord injuries.

What evidence suggests that this trial's treatments could be effective for spinal cord injury?

Research has shown that dorsal myelotomy and expansive duraplasty (DMED), a procedure participants in this trial may receive, can enhance recovery after spinal cord injuries. Studies have found that early pressure relief on the spinal cord aids recovery. Myelotomy procedures have succeeded in 80% of animal studies and have shown positive results in human studies, improving movement and sensation.

The trial also explores combining DMED with autologous nerve graft implantation (ANGI). This approach uses a person's own nerve tissue to facilitate nerve growth across injury sites. It has successfully bridged gaps in the spinal cord and supported nerve regrowth. Overall, these treatments show promise in aiding recovery from spinal cord injuries. ^{1 6 7 8 9}

Who Is on the Research Team?

Francis H Farhadi, MD, PhD

Principal Investigator

University of Kentucky Neurosurgery

Are You a Good Fit for This Trial?

This trial is for adults aged 18-80 with acute traumatic spinal cord injury (SCI) at certain levels of the spine, who can consent and have surgery within 48 hours post-injury. Excluded are those with mild SCI, other serious conditions or mental impairments, substance abuse issues, pregnancy, involvement in another SCI study or if anterior-only spinal surgery is suitable.

Inclusion Criteria

I do not have any other life-threatening conditions.

I do not have sepsis.

My spinal cord injury is between my neck and mid-back without piercing the cord.

Exclusion Criteria

Other illness (including mental disorder) that could preclude accurate medical and neurological evaluation (at discretion of the principal investigator)

Unable to commit to the follow-up schedule

My spinal cord injury is moderate to mild, allowing some movement or sensation.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants undergo dorsal myelotomy and expansive duraplasty (DMED) with or without autologous nerve graft implantation (ANGI)

12 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 months

What Are the Treatments Tested in This Trial?

Interventions

• Nerve Graft Implantation
• Spinal Decompression

Trial Overview The study tests two surgical methods for treating acute SCI: DMED alone versus DMED combined with ANGI. It's a small-scale test to see if adding nerve grafts helps recovery. Participants won't know which treatment they get and neither will the assessors evaluating them.

How Is the Trial Designed?

Group I: DMED Active Control 1 Intervention

Dorsal myelotomy and expansive duraplasty (DMED) only.

Group II: DMED + ANGI Active Control 2 Interventions

Dorsal myelotomy and expansive duraplasty (DMED) and supplemental autologous nerve graft implantation (ANGI).

Who Is Running the Clinical Trial?

University of Kentucky

Lead Sponsor

Trials

198

Recruited

224,000+

H. Francis Farhadi

Lead Sponsor

Trials

4

Recruited

410+

Francis Farhadi

Lead Sponsor

Trials

2

Recruited

330+

Spinal Cord and Brain Injury Research Center (SCOBIRC)

Collaborator

Trials

1

Recruited

10+

Published Research Related to This Trial

In a study involving two patients with complete cervical spinal cord injury, the addition of durotomy and expansile duraplasty to standard decompression and fixation procedures resulted in significant clinical improvement, with both patients improving from ASIA A to ASIA D.

This suggests that durotomy and duraplasty may be beneficial interventions for patients with complete spinal cord injuries undergoing surgical treatment, potentially preventing further injury and promoting recovery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Expansive Duraplasty - Simple Technique with Promising Results in Complete Cervical Spinal Cord Injury: A Preliminary Study. Garg, K., Agrawal, D., Hurlbert, RJ.[2022]

In a study involving 72 rats with acute cervical spinal cord injury, the combination of decompressive durotomy and dural allograft placement led to better functional recovery compared to decompression alone.

Histological analysis showed that the group receiving the dural allograft had significantly reduced scar formation and inflammation, as well as smaller cavitation sizes, indicating that this approach may enhance healing after spinal cord injuries.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Role of early surgical decompression of the intradural space after cervical spinal cord injury in an animal model. Smith, JS., Anderson, R., Pham, T., et al.[2022]

This case report describes a rare instance of dorsal herniation of the spinal cord in a 57-year-old male following surgery for a benign cyst, marking only the fifth reported case in the thoracolumbar spine.

Surgical reduction of the herniated cord and direct closure of the defect led to a full recovery, suggesting that effective management can be achieved without the need for a dural patch.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Posterior spinal cord herniation: a novel occurrence following surgery for an intramedullary cyst at the thoracolumbar junction. Zakaria, R., Ellenbogen, JR., Grewal, IS., et al.[2021]

In a study of 21 patients with acute severe traumatic spinal cord injury, the combination of laminectomy and duroplasty resulted in significantly better spinal cord decompression and improved physiological parameters compared to laminectomy alone.

The laminectomy+duroplasty group showed lower intraspinal pressure and higher spinal cord perfusion pressure, indicating better blood flow and pressure reactivity, although there were some complications like cerebrospinal fluid leaks that were manageable.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Expansion duroplasty improves intraspinal pressure, spinal cord perfusion pressure, and vascular pressure reactivity index in patients with traumatic spinal cord injury: injured spinal cord pressure evaluation study. Phang, I., Werndle, MC., Saadoun, S., et al.[2022]

Transplanting autoperipheral nerve tissues into chronic spinal cord injury sites in rats led to significant survival and integration of the grafts, promoting nerve regeneration and repair of the spinal cord.

Rats that received the nerve grafts showed improved motor function in their hind legs compared to the control group, indicating that this method could be an effective approach for treating chronic spinal cord injuries.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Experimental study of peripheral nerve grafts for repairing of chronic spinal cord injury in adult rats]. Ma, WQ., Zhang, SC., Li, M., et al.[2008]

Durotomy, a surgical procedure to relieve spinal cord compression, has shown positive effects on neurological function in 92.3% of human studies and 83.3% of animal studies, suggesting it may be a safer and more effective option than myelotomy.

In contrast, myelotomy has only shown effectiveness in 80% of animal studies and has had limited positive results in humans, with only one clinical study reporting improvements in motor and sensory function. More randomized controlled trials are needed to clarify the effectiveness of both procedures.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of durotomy versus myelotomy in the repair of spinal cord injury. Telemacque, D., Zhu, FZ., Ren, ZW., et al.[2023]

Two cases of 35-year-old males with traumatic paraplegia developed Sub-acute Post-Traumatic Ascending Myelopathy (SPAM) after surgical decompression, showing that this is a potential complication following such procedures.

Both patients showed significant neurological improvement after receiving steroid treatment, highlighting the importance of prompt intervention and careful surgical techniques to minimize spinal cord handling during decompression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Subacute post-traumatic ascending myelopathy (SPAM): two cases of SPAM following surgical treatment of thoracolumbar fractures. Farooque, K., Kandwal, P., Gupta, A.[2014]

Monitoring intraspinal pressure through surgically implanted probes can provide critical information about spinal cord health and may improve management of acute spinal cord injuries.

Expansion duraplasty is being tested in a randomized controlled trial (DISCUS) as a potential effective treatment for severe traumatic cervical spinal cord injuries, addressing the limitations of traditional decompression methods.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Acute, Severe Traumatic Spinal Cord Injury: Monitoring from the Injury Site and Expansion Duraplasty. Saadoun, S., Papadopoulos, MC.[2022]

Acute surgical decompression, stabilization, and fusion for spinal cord injury is a safe procedure, with no patients experiencing worsened conditions post-surgery.

Patients with some preserved function and myelographic defects showed better recovery outcomes compared to those with normal myelograms who did not undergo surgery, indicating that surgery is beneficial for certain candidates.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Early surgical management of acute spinal cord injury. Ransohoff, J., Benjamin, V., Flamm, ES.[2004]

In a study of 23 patients with traumatic spinal injuries, a combined technique of spinal shortening and interbody fusion effectively decompressed the spinal cord and achieved significant correction of spinal deformities, with the Cobb angle improving from 26 to 4 degrees post-surgery.

The procedure resulted in solid fusion and anatomical reconstruction in all patients, demonstrating its efficacy in managing unstable dorsal and lumbar injuries while minimizing loss of correction.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Spinal shortening and monosegmental posterior spondylodesis in the management of dorsal and lumbar unstable injuries. Aly, TA.[2021]

Citations

1. sciencedirect.com sciencedirect.com/science/article/pii/S187874792301543X

Peripheral Nerve Grafts Support Regeneration after Spinal ... This review focuses on results obtained from grafting peripheral nerve segments into the injured spinal cord, but it would be remiss not to mention that ...

2. inflammregen.biomedcentral.com inflammregen.biomedcentral.com/articles/10.1186/s41232-024-00319-4

Novel artificial nerve transplantation of human iPSC-derived ... After transplantation, the neurite bundle-derived artificial nerves exerted significant therapeutic effects, both functionally and histologically.

3. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0014488620302570

The evolution of nerve transfers for spinal cord injury Advancements in autologous peripheral nerve transplantation care: a review of strategies and practices to facilitate recovery. 2024, Frontiers in Neurology ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10959128/

Advancements in autologous peripheral nerve transplantation ... Autologous peripheral nerve transplantation, a pioneering technique in nerve injury treatment, has demonstrated remarkable progress.

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9097274/

Advancing Peripheral Nerve Graft Transplantation for ... A PNG can thus be suited to bridge axons long distances across an injury site and restore long tracts in incomplete SCI.

6. acta.tums.ac.ir acta.tums.ac.ir/index.php/acta/article/download/4335/4535

Safety of Intramedullary Autologous Peripheral Nerve ... Abstract- Many experimental studies have reported behavioral improvement after transplantation of peripheral nerve tissue into the contused spinal cord, ...

7. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/24442538/

Safety of intramedullary autologous peripheral nerve grafts ... Many experimental studies have reported behavioral improvement after transplantation of peripheral nerve tissue into the contused spinal cord, even in large ...

8. sciencedirect.com sciencedirect.com/science/article/abs/pii/S1465324924008272

Challenges in advancing Schwann cell transplantation for ... Numerous studies have tested their repair capabilities after spinal cord injury (SCI) [8], and the ability of transplanted cultured SCs to support regeneration ...

9. journals.lww.com journals.lww.com/co-transplantation/fulltext/2013/12000/clinical_translation_of_autologous_schwann_cell.10.aspx

Clinical translation of autologous Schwann cell... A few clinical studies have reported that Schwann cell transplantation appears safe. Compared with allogeneic cell transplants, autologous cells do not require ...