Metformin in Preventing Secondary Gliosis Following Acute Thoraco-Lumbar Spinal Cord Injury

Safety and Efficacy of Metformin in Preventing Secondary Gliosis Following Acute Thoraco-Lumbar Spinal Cord Injury: A Randomized, Double-Blinded, Placebo-Controlled Study.

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

Study Overview

• Status: Not yet recruiting
• Conditions: Spinal Cord Injury (SCI)
• Intervention / Treatment: Drug: Metformin; Drug: Placebo

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.

• Study Type: Interventional
• Enrollment (Estimated): 34
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Eman Swan, PHD; Phone Number: +201090111013; Email: eman.said@buc.edu.eg
• Study Contact Backup: Name: Saeed Alemam, PHD; Phone Number: +201027345368; Email: Said.elemam@med.menofia.edu.eg

Study Locations

• Egypt
  • Menoufia
    • Shibīn al Kawm, Menoufia, Egypt, 32817
      • Neurosurgery department at Menoufia University hospitals at Menoufia University.
      • Contact: Said Elemam, PHD; Phone Number: +201027345368; Email: Said.elemam@med.menofia.edu.eg

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Metformin; The metformin group will receive 1,000 mg of immediate-release metformin orally, twice daily	Drug: Metformin; Participants assigned to the metformin group will receive 1,000 mg of immediate-release metformin orally, twice daily; Other Names: Glucophage 1000 mg tablets
Placebo Comparator: Placebo; Participants in the placebo group will receive an identical-appearing placebo, administered orally, twice daily	Drug: Placebo; Participants in the placebo group will receive an identical-appearing placebo, administered orally, twice daily; Other Names: Metformin free tablets

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Neurological recovery	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	2 weeks, and 3-months postoperatively.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pain intensity	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	at 2 weeks, and 3-months postoperatively
Neuropathic Pain character	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	at 2 weeks, and 3-months postoperatively

Collaborators and Investigators

• Sponsor: Badr University

Study record dates

Study Major Dates

• Study Start (Estimated): January 1, 2026
• Primary Completion (Estimated): January 1, 2026
• Study Completion (Estimated): February 1, 2026

Study Registration Dates

• First Submitted: November 19, 2025
• First Submitted That Met QC Criteria: November 26, 2025
• First Posted (Estimated): December 9, 2025

Study Record Updates

• Last Update Posted (Estimated): December 9, 2025
• Last Update Submitted That Met QC Criteria: November 26, 2025
• Last Verified: November 1, 2025

More Information

Terms related to this study

• Keywords: Metformin; neuroprotection; gliosis; spinal cord injury,; , randomized controlled trial
• Additional Relevant MeSH Terms: Central Nervous System Diseases; Nervous System Diseases; Wounds and Injuries; Pathologic Processes; Trauma, Nervous System; Spinal Cord Diseases; Pathological Conditions, Signs and Symptoms; Spinal Cord Injuries; Gliosis; Organic Chemicals; Biguanides; Guanidines; Amidines; Metformin
• Other Study ID Numbers: 9/2025NEUS6

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Data is available with corresponding author on reasonable request

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No