Minocycline in Acute Spinal Cord Injury (MASC)

Study Overview
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Brief Summary
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The objective of this study is to assess the efficacy of IV minocycline in improving neurological and functional outcome after acute non-penetrating traumatic spinal cord injury (SCI). The primary hypothesis is that intravenous minocycline twice daily (800 mg initial dose tapered to 400 mg by 100 mg at each dose then administered to the end of day 7) administered to subjects with acute traumatic non-penetrating cervical SCI starting within 12 hours of injury will improve motor recovery as assessed by the International Standards for Neurologic Classification of Spinal Cord Injury - ISNCSCI (a.k.a. ASIA) neurological examination measured between 3 months and 1 year post-injury, compared to placebo. The secondary hypotheses are that the above minocycline treatment will also results in improvement in ASIA sensory improvement, in ASIA grade and in functional outcome as assessed by Spinal Cord Independence Measure (SCIM) and Short Form 36 (SF-36), compared to placebo. In addition the effect of minocycline on neurological and functional outcome after SCI is expected to be more pronounced in those subjects with motor incomplete SCI compared to those with motor compete SCI. A subgroup analysis will be undertaken to examine this hypothesis.

Official Title
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Phase III Study of Minocycline in Acute Spinal Cord Injury

Conditions
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Spinal Cord Injuries

Intervention / Treatment
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* Drug: Minocycline
* Drug: Placebo
* Procedure: Surgical spinal cord decompression
* Procedure: Maintenance of minimum mean arterial pressure (MAP)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 16 or over Acute traumatic non-penetrating cervical SCI involving neurological levels as defined by the ASIA neurological examination between C0 and C8 and resulting in a detectable change in the ASIA motor assessment Patient English speaking and able to provide informed consent Randomization and administration of first dose (drug or placebo) within 12 hours of injury. Exclusion Criteria: History of systemic lupus erythematosus (SLE) Pre-existing hepatic or renal disease Tetracycline hypersensitivity Pregnancy or breast feeding Isolated radicular motor deficit Significant leucopenia (white blood cell count < 1⁄2 times the lower limit of normal) at screening Elevated liver function tests (AST, ALT, alkaline phosphatase, or total bilirubin > 2 times the upper limit of normal) at screening Presence of systemic disease that might interfere with patient safety, compliance or evaluation of the condition under study (e.g. insulin-dependent diabetes, Lyme disease, clinically significant cardiac disease, HIV, HTLV-1) Associated traumatic conditions interfering with informed consent or outcome assessment (e.g. closed head injury, liver contusion) Known uncorrected severe coronary artery disease or evidence of active coronary ischemia (ECG changes, positive Troponin) will be excluded, as they may not tolerate the standardized protocol for hemodynamic management

Ages Eligible for Study
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Minimum Age: 16 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Minocycline<br>Minocycline twice daily infused over 30 minutes through central venous access as follows 800 mg + 700 mg on Day 1, 600 mg + 500 mg on Day 2, and 400 mg thereafter from Day 3 thru Day 7 | Drug: Minocycline<br> <br> Procedure: Surgical spinal cord decompression<br>* Surgical decompression by means at the discretion of the clinical management team will occur within 24 hours of injury in all subjects. Stabilization will occur at that time but may also include further interventions at a later time.<br>Procedure: Maintenance of minimum mean arterial pressure (MAP)<br>* Standardized hemodynamic management protocol aimed at maintaining MAP ≥ 85 mm Hg for 7 days using volume augmentation with isotonic crystalloid followed by inotropic support if needed will be applied to all subjects.<br>|
| Placebo Comparator: Placebo<br>250 ml normal saline and infused over 30 minutes through central venous access twice daily for 7 days | Drug: Placebo<br> <br> Procedure: Surgical spinal cord decompression<br>* Surgical decompression by means at the discretion of the clinical management team will occur within 24 hours of injury in all subjects. Stabilization will occur at that time but may also include further interventions at a later time.<br>Procedure: Maintenance of minimum mean arterial pressure (MAP)<br>* Standardized hemodynamic management protocol aimed at maintaining MAP ≥ 85 mm Hg for 7 days using volume augmentation with isotonic crystalloid followed by inotropic support if needed will be applied to all subjects.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| ASIA Motor Recovery | Motor recovery (improvement from baseline examination) as assessed by the International Standards for Neurologic Classification of Spinal Cord Injury - ISNCSCI (a.k.a. ASIA) neurological examination measured between 3 months and 1 year post-injury, compared to placebo. | assessed at time points: day 1,3,7, week 3,6, month 3,6,12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| ASIA sensory recovery | Sensory recovery (improvement from baseline) as assessed by the International Standards for Neurologic Classification of Spinal Cord Injury - ISNCSCI (a.k.a. ASIA) neurological examination measured between 3 months and 1 year post-injury, compared to placebo | assessed at time points: day 1,3,7 week 3,6, months 3,6,12 | 
| Spinal cord Independence measure (SCIM) | Functional outcome as assessed by the Spinal cord independence Measure assessment at specified time points. | assessed at time points: week 6, month 3,6,12 | 
| Short Form 36 (SF-36) | functional outcome as assessed by the short form 36 (SF-36) quality of Life assessment at specified time points. | assessed at time points: week 6, month 3,6,12 | 
| ASIA impairment grade | change in ASIA impairment grade at specified time points | assessed at time points: day 1,3,7 week 3,6 month 3,6,12 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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minocycline, randomized control trial, phase 3, spinal cord injury