Clinical trial NCT00559494: Minocycline and Perfusion Pressure Augmentation in Acute Spinal Cord Injury
Official title: A Pilot Study to Assess Clinical Safety and Tolerance of Minocycline and Spinal Perfusion Pressure Augmentation in Acute Spinal Cord Injury
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Spinal Cord Injuries
Keywords: complete spinal cord injury
incomplete spinal cord injury
central cord spinal cord injury
traumatic
Lead sponsor: University of Calgary
Sponsor class: OTHER
Collaborators: name: Paralyzed Veterans of America
name: American Association of Neurological Surgeons
name: Hotchkiss Brain Institute, University of Calgary
First posted: 2007-11-16
Enrollment: 52
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: While research in animal models of spinal cord injury have provided many promising insights, human studies have failed to produce effective therapies. We propose to investigate the drug Minocycline (a metalloproteinase inhibitor) for the treatment of spinal cord injured patients aiming to limit neurological injury and improve neurological outcome. This drug influences several secondary injury mechanisms implicated in spinal cord injury and has been effective in improving outcome after spinal cord injury in animal models. We also propose to examine the safety and feasibility of spinal cord perfusion pressure augmentation with a protocol of IV fluids and inotrope medications versus standard maintenance of mean arterial pressure in subjects who exhibit a decrease in perfusion pressure to less than 75 mmHg. The purpose of this pilot study is 1) to evaluate the feasibility of a clinical trial protocol for Minocycline in patients with acute spinal cord injury, and 2) to ensure adequate drug dosing and metabolic effect. After undergoing a process of informed consent, patients agreeing to participate in the study will be randomized to placebo or treatment groups in a double-blind fashion. Clinical neurological examinations, patient-reported quality of life, and functional independence categorization will be combined with serum and cerebrospinal fluid laboratory investigations to establish some of the pharmacological properties and the safety profile of this medication in this group of patients. In addition, patient tolerance to the dosing regimen will be assessed. The results of this study will provide the preliminary data necessary to plan for a larger prospective, randomized, controlled, double-blind clinical trial to assess efficacy and to further assess safety.


Eligibility criteria: Inclusion Criteria:

* Age 16 or over
* Motor complete or motor incomplete acute spinal cord injury involving bony spinal levels between C0 and T11
* Patient able to provide informed consent
* Randomization and commencement of administration of first drug dose within 12 hours of injury
* surgical decompression if needed to be performed within 24 hours of the injury
* subjects exhibiting spinal cord perfusion pressure (lumbar drain transduced pressure - mean arterial pressure)\> 75 mmHg will be randomized to active augmentation protocol versus maintenance of mean arterial pressure

Exclusion Criteria:

* Acute spinal cord injury \>12 hours old
* Isolated sensory deficit, motor intact
* Isolated cauda equina injury or injury at bony level T12 or below
* History of systemic lupus erythematosus (SLE)
* Pre-existing hepatic or renal disease
* Tetracycline hypersensitivity
* Pregnancy or breast feeding
* Isolated sensory deficit
* Isolated radicular motor deficit
* Significant leukopenia (white blood cell count \< ½ 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 from SCPP randomization

Primary outcomes:
measure: Protocol compliance, feasibility and adverse events
timeFrame: 2 years
Secondary outcomes:
measure: American Spinal Injury Association - motor score (primary clinical outcome) and sensory scores
timeFrame: 2 years
measure: Short Form 36 - Quality of Life Assessment
timeFrame: 2 years
measure: Functional Independence Measure
timeFrame: 2 years
measure: London Handicap Scale
timeFrame: 2 years
measure: Spinal Cord Injury Measure
timeFrame: 2 years
measure: CSF collection (6/day) and biochemical assays
timeFrame: 7 days
measure: Sequential Anatomical MRI
timeFrame: 1 year
Other outcomes:
Locations:
city: Calgary
country: Canada
facility: Foothills Medical Centre
state: Alberta
Study officials:
affiliation: University of Calgary
name: Steven Casha, MD PhD FRCSC
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Calgary
name: R. John Hurlbert, MD PhD FRCSC
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Calgary
name: David Zygun, MD MSc
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.
citation: Carnini A, Casha S, Yong VW, Hurlbert RJ, Braun JE. Reduction of PrP(C) in human cerebrospinal fluid after spinal cord injury. Prion. 2010 Apr-Jun;4(2):80-6. doi: 10.4161/pri.4.2.11756. Epub 2010 Apr 10.