Safety and Efficacy of Metformin in Preventing Secondary Gliosis Following Acute Thoraco-Lumbar Spinal Cord Injury: A Randomized, Double-Blinded, Placebo-Controlled Study.
试验速览
- 阶段
- 4 期
- 状态
- 尚未招募
- 发起方
- 入组人数
- 34
- 试验地点
- 1
- 主要终点
- Neurological recovery
研究概览
简要总结
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
详细描述
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).
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Double (Participant, Care Provider)
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •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.
研究组 & 干预措施
Metformin
The metformin group will receive 1,000 mg of immediate-release metformin orally, twice daily
干预措施: Metformin (Drug)
Placebo
Participants in the placebo group will receive an identical-appearing placebo, administered orally, twice daily
干预措施: Placebo (Drug)
结局指标
主要结局
Neurological recovery
时间窗: 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
次要结局
- Pain intensity(at 2 weeks, and 3-months postoperatively)
- Neuropathic Pain character(at 2 weeks, and 3-months postoperatively)
研究者
Eman Said Sawan
Lecturer of Clinical Pharmacy, Faculty of Pharmacy
Badr University