Clinical trial NCT01828203: Minocycline in Acute Spinal Cord Injury (MASC)
Official title: Phase III Study of Minocycline in Acute Spinal Cord Injury
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE3
Conditions: Spinal Cord Injuries
Keywords: minocycline
randomized control trial
phase 3
spinal cord injury
Lead sponsor: Rick Hansen Institute
Sponsor class: OTHER
Collaborators: name: University of Calgary
name: Alberta Paraplegic foundation
First posted: 2013-04-10
Enrollment: 248
Sex: ALL
Minimum age (years): 16
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

Primary outcomes:
measure: ASIA Motor Recovery
timeFrame: assessed at time points: day 1,3,7, week 3,6, month 3,6,12
Secondary outcomes:
measure: ASIA sensory recovery
timeFrame: assessed at time points: day 1,3,7 week 3,6, months 3,6,12
measure: Spinal cord Independence measure (SCIM)
timeFrame: assessed at time points: week 6, month 3,6,12
measure: Short Form 36 (SF-36)
timeFrame: assessed at time points: week 6, month 3,6,12
measure: ASIA impairment grade
timeFrame: assessed at time points: day 1,3,7 week 3,6 month 3,6,12
Other outcomes:
measure: effect of injury severity
timeFrame: as per primary and secondary outcomes
Locations:
city: Brisbane
country: Australia
facility: Princess Alexandra Hospital
state: Queensland
city: Calgary
country: Canada
facility: Foothills Medical Centre
state: Alberta
city: Edmonton
country: Canada
facility: University of Alberta & Royal Alexandra Hospitals
state: Alberta
city: Halifax
country: Canada
facility: Queen Elizabeth II Health Sciences Centre
state: Nova Scotia
city: London
country: Canada
facility: London Health Sciences Centre - Victoria Hospital
state: Ontario
city: Ottawa
country: Canada
facility: The Ottawa Hospital - Civic Campus
state: Ontario
city: Montreal
country: Canada
facility: Hôpital Du Sacré-Cœur de Montréal
state: Quebec
Study officials:
affiliation: University of Calgary
name: Steve Casha, MD PhD FRCSC
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.