Clinical Trial Details
— Status: Recruiting
Administrative data
| NCT number |
NCT06243211 |
| Other study ID # |
91630 |
| Secondary ID |
|
| Status |
Recruiting |
| Phase |
N/A
|
| First received |
|
| Last updated |
|
| Start date |
April 19, 2024 |
| Est. completion date |
December 31, 2026 |
Study information
| Verified date |
May 2024 |
| Source |
University of Kentucky |
| Contact |
Francis H Farhadi, MD, PhD |
| Phone |
859-323-5661 |
| Email |
francis.farhadi[@]uky.edu |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial Summary
This is a single-blinded (with outcome assessors blinded to treatment allocation), 12-month
pilot study to evaluate of the safety, feasibility, and preliminary efficacy of dorsal
myelotomy and expansive duraplasty performed either without or with autologous nerve graft
implantation after acute traumatic spinal cord injury.
Ten participants will be allocated to receive either DMED (n=5) or DMED + ANGI (n=5) based on
a block design. Participants and assessors will be blinded to group allocation. Excess sural
nerve samples will be collected for banking/analysis (may include proteomic, culturing,
genomic, cellular analysis).
Description:
Spinal cord injury (SCI) is associated with devastating personal burdens including paralysis,
sensory changes, autonomic dysfunction, and chronic debilitating pain. Few effective
treatments have been developed with standard of care consisting of state-of-the-art
neurocritical care, timely surgical decompression, and rehabilitation. While a variety of
novel neuroprotective and neuroregenerative approaches have been posited, clinical trials to
date have failed to demonstrate associated clinical benefits.
Current therapies are primarily aimed at reducing secondary injury processes, which are
related to inflammation and ischemia, that persist over days-to-weeks following the primary
mechanical insult. Intraparenchymal progressive hemorrhagic necrosis and swelling within the
restrictive physical barrier of the pial and dural layers leads to further compression and
ischemia, propagating the secondary injury cascade.
Early surgical bony decompression following SCI is thought to improve clinical outcomes,
specifically after cervical-level injuries.
While few developments have been made in actual surgical techniques beyond bony
decompression, early reports suggest that reduction of intraspinal pressure (ISP) could
reduce secondary injury. Long-recognized but not clinically employed techniques to reduce ISP
involve fashioning a dorsal midline myelotomy to allow for intramedullary decompression of
hematoma and necrotic tissue and expansion of the dural compartment by opening the dura and
sewing in of an expansive patch.
Corollary techniques have long been standard-of-care following cranial trauma: removal of the
calvarial bone, evacuation of hematoma, expansive dural closure, and treatment of
intra-cranial pressure have been proven effective in several randomized clinical trials.
Each of these steps are also at times used in other domains of spinal surgery, specifically
oncologic resections. Despite having been demonstrated as an option to manage spinal trauma
by Allen over a century ago, these techniques have not been widely studied or applied in
modern spinal surgery.
The data obtained from this study will be used to inform and advance the practice of spinal
cord decompression and cell-based therapies following acute SCI. Information on microsurgical
technique adjustments, neurocritical nursing care standards, medical management, and ISP
metrics may prove invaluable in advancing the feasible and safe aspects of these
interventions.
SCI is a severely disabling neurological condition leading to impaired mobility, pain, and
autonomic dysfunction. As potentially neuroprotective strategies, dorsal myelotomy and
expansive duraplasty (DMED) along with cell-based therapies (e.g., autologous nerve tissue
graft implantation, ANGI) are recognized as promising candidates to promote functional
recovery. However, no trials of these therapies in patients have yet provided reproducible
evidence of clinical efficacy, challenged by small effect sizes, low immune suppression, and
low sensitivity study designs.
This pilot study design represents the first stage of a systematic evaluation of DMED +/-
ANGI performed in the early/acute phase after SCI. Performance of DMED at early timepoints is
expected to have the greatest impact on minimizing the deleterious effect of increased ISP
and secondary injury due to PHN, which is known to be ongoing over the first hours and days
after SCI. Assessment of the feasibility and safety of performing DMED +/- ANGI represent a
critical first step prior to engaging in any larger-scale multicenter evaluations of
efficacy.
Future larger-scale phases of the study will focus on elucidating the efficacy of these
interventions in protecting against secondary neuronal injury processes and in improving
function after SCI. The pilot data generated from this study will prove crucial in seeking a
larger award from the National Institutes of Health (NIH) and other funding sources.
While refinements and combined therapies may prove useful, widespread clinical translation of
currently employed cell transplantation protocols will likely face critical logistic and
safety-related obstacles, particularly in the most opportune acute phase after SCI. The need
for cell culturing and concomitant immunosuppression are fraught with potential
complications, especially considering the relative immune compromised state and elevated risk
of infections in the acute phase after SCI that can independently negatively impact
neurological outcomes.
