Minocycline in Acute Spinal Cord Injury (MASC)

Spinal Cord Injuries Clinical Trial

Official title:

Phase III Study of Minocycline in Acute Spinal Cord Injury

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT01828203
• Other study ID #: RHI-1005
• Status: Recruiting
• Phase: Phase 3
• First received: April 5, 2013
• Last updated: October 29, 2014
• Start date: June 2013
• Est. completion date: June 2018

Study information

• Verified date: October 2014
• Source: Rick Hansen Institute
• Contact: Steve Casha, MD PhD FRCSC
• Phone: 1-403-944-3405
• Email: scasha[@]ucalgary.ca
• Is FDA regulated: No
• Health authority: Canada: Health Canada
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 248
• Est. completion date: June 2018
• Est. primary completion date: June 2018
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 16 Years and older

Eligibility

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 Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Spinal Cord Injuries

Intervention

Drug:
• Minocycline

• 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.
• 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.

Locations

Country	Name	City	State
Australia	Princess Alexandra Hospital	Brisbane	Queensland
Canada	Foothills Medical Centre	Calgary	Alberta
Canada	University of Alberta & Royal Alexandra Hospitals	Edmonton	Alberta
Canada	Queen Elizabeth II Health Sciences Centre	Halifax	Nova Scotia
Canada	London Health Sciences Centre - Victoria Hospital	London	Ontario
Canada	Hôpital Du Sacré-Cœur de Montréal	Montreal	Quebec
Canada	The Ottawa Hospital - Civic Campus	Ottawa	Ontario

Sponsors (3)

Lead Sponsor	Collaborator
Rick Hansen Institute	Alberta Paraplegic foundation, University of Calgary

Countries where clinical trial is conducted

Australia,  Canada, 

References & 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	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	No
Primary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No