Spinal Cord Injury (SCI)
Conditions
Keywords
Metformin, spinal cord injury,, gliosis, , randomized controlled trial, neuroprotection
Brief summary
Background: Spinal cord injury (SCI) is a major global health problem, with thoraco-lumbar injuries often leading to paraplegia and incomplete neurological recovery. The glial scar, resulting from astrocyte activation at the injury site, constitutes a major barrier to axon regeneration. Given the limitations of current treatments, there is an urgent need for new interventions to improve outcomes. Metformin, a common drug for diabetes, shows promising potential as a neuroprotective agent in preclinical SCI models, where it improves motor function and reduces pain and glial scar formation. Its safety in acute neurological injury has also been supported in a recent human trial for severe traumatic brain injury. Objective: To test the safety and efficacy of metformin in acute thoraco-lumbar SCI, focusing on neurological and functional outcomes as well as DTI metrics of spinal cord integrity. Methods. Study Design. Randomized, double-blinded, placebo-controlled study. Population: Participants that will be admitted during the time of the study to Neurosurgery department at Menoufia University hospitals at Menoufia University. Setting: Neurosurgery department at Menoufia University hospitals at Menoufia University. Keywords: Metformin, spinal cord injury, gliosis, randomized controlled trial, neuroprotection
Detailed description
Study Design. Randomized, double-blinded, placebo-controlled study. Randomization and Blinding. Participants will be randomly assigned to either the metformin or placebo group in a 1:1 ratio using block randomization. A computer-generated randomization sequence will be created with the R software (version 4.4.1) and the blockrand package(7). This sequence will be securely stored and accessible only to the study statistician. Treatment packets will be pre-labeled with unique numbers matching the randomization sequence. When a patient qualifies for the study, they will receive a numbered packet corresponding to their assignment. To ensure objectivity, neither participants nor study staff will know which number corresponds to metformin or placebo-only the statistician will have access to this information. Setting: Neurosurgery department at Menoufia University hospitals at Menoufia University. Instruments: We will assess the patient using AISA grade, Visual Analog Scale (VAS) and the Neuropathic Pain Symptom Inventory (NPSI) (8-10). Data collection: It will be done by data collaborators under the leadership of the investigators in: Neurosurgery department at Menoufia University hospitals at Menoufia University.
Interventions
DRUGMetformin
Participants assigned to the metformin group will receive 1,000 mg of immediate-release metformin orally, twice daily
DRUGPlacebo
Participants in the placebo group will receive an identical-appearing placebo, administered orally, twice daily
Sponsors
Badr University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Caregiver)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* Adults aged 18-65 years, who had acute, non-penetrating thoraco-lumbar SCI (T1-conus medullaris), with new neurological deficits. * Injury occurred within the past 24 hours before enrollment. * American Spinal Injury Association (ASIA) Impairment Scale grade B-D. * Able to undergo MRI of the spine. * Informed consent provided by patient or legal representative.
Exclusion criteria
* Major spinal transaction or cervical spinal cord injury. * Prior spinal surgery or pre-existing spinal pathology (e.g., kyphosis, tumors). * Concomitant severe traumatic brain injury (Glasgow Coma Scale \< 13) or other CNS injury that would confound neurological assessment. * Known diabetes mellitus (type 1 or 2) or current use of metformin. * Penetrating spinal injury (e.g. gunshot, stab wound). * Implanted metallic devices or conditions precluding MRI. * Pregnancy or breastfeeding. * Severe comorbidities (e.g. end-stage liver disease, renal failure with eGFR\<30 mL/min). * Known allergy to metformin. * Uncontrolled infection or sepsis at presentation.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Neurological recovery | 2 weeks, and 3-months postoperatively. | Comparison of postoperative American Spinal Injury Association (ASIA) Impairment Scale grade ranging from A to E where Grade A= Complete spinal cord injury and Grade E=Normal function |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Pain intensity | at 2 weeks, and 3-months postoperatively | Comparison of postoperative patient-reported pain using Visual Analog Scale (VAS) that is ranging from 0-10 score where 0=no pain and10= the worst possible pain |
| Neuropathic Pain character | at 2 weeks, and 3-months postoperatively | Comparison of postoperative Neuropathic character of pain using Neuropathic Pain Symptom Inventory (NPSI) scale ranging from 0-10 score where 0=no pain and 10= the worst possible pain |
Countries
Egypt
Contacts
Primary ContactEman Swan, PHD
Backup ContactSaeed Alemam, PHD
Outcome results
None listed