Minocycline in Acute Spinal Cord Injury (MASC)

NCT01828203 | Unknown Phase 3 DMC

• 1 other identifier: RHI-1005
• Study Type: interventional
• Target: 248
• Locations: 2 countries
• Sites: 7

Brief Summary

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.

Conditions

Spinal Cord Injuries

Keywords

minocycline; randomized control trial; phase 3; spinal cord injury

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (4)

• ASIA sensory recovery

  assessed at time points: day 1,3,7 week 3,6, months 3,6,12

• Spinal cord Independence measure (SCIM)

  assessed at time points: week 6, month 3,6,12

• Short Form 36 (SF-36)

  assessed at time points: week 6, month 3,6,12

• ASIA impairment grade

  assessed at time points: day 1,3,7 week 3,6 month 3,6,12

Other Outcomes (1)

• effect of injury severity

  as per primary and secondary outcomes

Study Arms (2)

Minocycline

EXPERIMENTAL

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; Procedure: Maintenance of minimum mean arterial pressure (MAP)

Placebo

PLACEBO COMPARATOR

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; Procedure: Maintenance of minimum mean arterial pressure (MAP)

Interventions

Minocycline DRUG

Minocycline

Placebo DRUG

Placebo

Surgical spinal cord decompression PROCEDURE

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.

Minocycline; Placebo

Maintenance of minimum mean arterial pressure (MAP) PROCEDURE

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.

Minocycline; Placebo

Eligibility Criteria

• Age: 16 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Rick Hansen Institute: lead
• University of Calgary: collaborator
• Alberta Paraplegic foundation: collaborator

Study Sites (7)

Princess Alexandra Hospital

Brisbane, Queensland, Australia

RECRUITING

Foothills Medical Centre

Calgary, Alberta, T2N 2T9, Canada

RECRUITING

University of Alberta & Royal Alexandra Hospitals

Edmonton, Alberta, Canada

RECRUITING

Queen Elizabeth II Health Sciences Centre

Halifax, Nova Scotia, Canada

NOT YET RECRUITING

London Health Sciences Centre - Victoria Hospital

London, Ontario, Canada

RECRUITING

The Ottawa Hospital - Civic Campus

Ottawa, Ontario, Canada

NOT YET RECRUITING

Hôpital Du Sacré-Cœur de Montréal

Montreal, Quebec, Canada

NOT YET RECRUITING

Related Publications (1)

• 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.

  PMID: 22505632 BACKGROUND

MeSH Terms

Conditions

Spinal Cord Injuries; cyclopia sequence

Interventions

Minocycline

Condition Hierarchy (Ancestors)

Spinal Cord Diseases; Central Nervous System Diseases; Nervous System Diseases; Trauma, Nervous System; Wounds and Injuries

Intervention Hierarchy (Ancestors)

Tetracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds

Study Officials

• Steve Casha, MD PhD FRCSC

  University of Calgary

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Steve Casha, MD PhD FRCSC

CONTACT

1-403-944-3405; scasha@ucalgary.ca

John Hurlbert, MD PhD FRCSC FACS

CONTACT

1-403-944-4496; jhurlber@ucalgary.ca

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Study Record Dates

• First Submitted: April 5, 2013
• First Posted: April 10, 2013
• Study Start: June 1, 2013
• Primary Completion: June 1, 2018
• Study Completion: June 1, 2018
• Last Updated: October 30, 2014

Record last verified: 2014-10

Locations

CA (6); AU (1)