Minocycline in Acute Spinal Cord Injury (MASC)

Phase III Study of Minocycline in Acute Spinal Cord Injury

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.

Study Overview

• Status: Unknown
• Conditions: Spinal Cord Injuries
• Intervention / Treatment: Drug: Placebo; Drug: Minocycline; Procedure: Surgical spinal cord decompression; Procedure: Maintenance of minimum mean arterial pressure (MAP)

• Study Type: Interventional
• Enrollment (Anticipated): 248
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Steve Casha, MD PhD FRCSC; Phone Number: 1-403-944-3405; Email: scasha@ucalgary.ca
• Study Contact Backup: Name: John Hurlbert, MD PhD FRCSC FACS; Phone Number: 1-403-944-4496; Email: jhurlber@ucalgary.ca

Study Locations

• Australia
  • Queensland
    • Brisbane, Queensland, Australia
      • Recruiting
      • Princess Alexandra Hospital
      • Contact: Michael Schuetz, MD
• Canada
  • Alberta
    • Calgary, Alberta, Canada, T2N 2T9
      • Recruiting
      • Foothills Medical Centre
      • Contact: Steve Casha, MD PhD FRCSC; Phone Number: 1-403-944-3405; Email: scasha@ucalgary.ca
      • Contact: John Hurlbert, MD PhD FRCSC FACS; Phone Number: 1-403-944-4496; Email: jhurlber@ucalgary.ca
      • Principal Investigator: Steve Casha, MD PhD FRCSC
      • Sub-Investigator: John Hurlbert, MD PhD FRCSC FACS
      • Sub-Investigator: Bradley Jacobs, MD FRCSC
    • Edmonton, Alberta, Canada
      • Recruiting
      • University of Alberta & Royal Alexandra Hospitals
      • Contact: Andrew Nataraj, MD
  • Nova Scotia
    • Halifax, Nova Scotia, Canada
      • Not yet recruiting
      • Queen Elizabeth Ii Health Sciences Centre
      • Contact: Sean Christie, MD
  • Ontario
    • London, Ontario, Canada
      • Recruiting
      • London Health Sciences Centre - Victoria Hospital
      • Contact: Chris Bailey, MD
    • Ottawa, Ontario, Canada
      • Not yet recruiting
      • The Ottawa Hospital - Civic Campus
      • Contact: Eve Tsai, MD
  • Quebec
    • Montreal, Quebec, Canada
      • Not yet recruiting
      • Hôpital du Sacré-Coeur de Montreal

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Minocycline; 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; Procedure: Surgical spinal cord decompression; 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.; Procedure: Maintenance of minimum mean arterial pressure (MAP); 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.
Placebo Comparator: Placebo; 250 ml normal saline and infused over 30 minutes through central venous access twice daily for 7 days	Drug: Placebo; Procedure: Surgical spinal cord decompression; 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.; Procedure: Maintenance of minimum mean arterial pressure (MAP); 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.

What is the study measuring?

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
effect of injury severity	the sub groups of motor complete (ASIA A and B) and motor incomplete (ASIA C and D) will be examines for each of the primary and secondary outcomes in order to examine the relative efficacy of minocycline in these groups	as per primary and secondary outcomes

Collaborators and Investigators

• Sponsor: Rick Hansen Institute
• Collaborators: University of Calgary; Alberta Paraplegic foundation
• Investigators: Principal Investigator: Steve Casha, MD PhD FRCSC, University of Calgary

Publications and helpful links

General Publications

• Casha S, Zygun D, McGowan MD, Bains I, Yong VW, Hurlbert RJ. Results of a phase II placebo-controlled randomized trial of minocycline in acute spinal cord injury. Brain. 2012 Apr;135(Pt 4):1224-36. doi: 10.1093/brain/aws072.

Study record dates

Study Major Dates

• Study Start: June 1, 2013
• Primary Completion (Anticipated): June 1, 2018
• Study Completion (Anticipated): June 1, 2018

Study Registration Dates

• First Submitted: April 5, 2013
• First Submitted That Met QC Criteria: April 5, 2013
• First Posted (Estimate): April 10, 2013

Study Record Updates

• Last Update Posted (Estimate): October 30, 2014
• Last Update Submitted That Met QC Criteria: October 29, 2014
• Last Verified: October 1, 2014

More Information

Terms related to this study

• Keywords: spinal cord injury; randomized control trial; minocycline; phase 3
• Additional Relevant MeSH Terms: Central Nervous System Diseases; Nervous System Diseases; Trauma, Nervous System; Spinal Cord Diseases; Wounds and Injuries; Spinal Cord Injuries; Anti-Infective Agents; Anti-Bacterial Agents; Minocycline
• Other Study ID Numbers: RHI-1005