Official Title: “A Pilot Study to Assess Clinical Safety and Tolerance of Minocycline and Spinal Perfusion Pressure Augmentation in Acute Spinal Cord Injury”

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.

Study Type: Interventional

Study Design: Treatment, Randomized, Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Placebo Control, Parallel Assignment, Safety/Efficacy Study

Study Primary Completion Date: November 2010

Intervention(s) in this Clinical Trial

• Drug: Minocycline
  • Minocycline IV BID x 7 days (first 10 patients 200 mg/dose, subsequent patients adjusted based on pharmacodynamic profiling to 800 mg loading dose, tapered 100 mg each dose to 400 mg then maintain at 400mg until day 7)
• Drug: placebo
  • Normal saline 250cc via central line similar to minocycline arm administration protocol
• Procedure: SCPP augmentation
  • maintenance of spinal cord perfusion pressure at 75 mmHg with fluids and inotrope protocol
• Procedure: SCPP control
  • maintenance of Mean arterial pressure of >65 mmHg with fluids and inotropes protocol without spinal cord perfusion pressure as target or guiding therapy

Arms, Groups and Cohorts in this Clinical Trial

• Experimental: Minocycline
• Placebo Comparator: Placebo
• Experimental: SCPP augmentation
• Sham Comparator: SCPP control

Primary Measures

• Protocol compliance, feasibility and adverse events
  • Time Frame: 2 years
    Safety Issue?: Yes

Secondary Measures

• American Spinal Injury Association - motor score (primary clinical outcome) and sensory scores
  • Time Frame: 2 years
    Safety Issue?: No
• Short Form 36 - Quality of Life Assessment
  • Time Frame: 2 years
    Safety Issue?: No
• Functional Independence Measure
  • Time Frame: 2 years
    Safety Issue?: No
• London Handicap Scale
  • Time Frame: 2 years
    Safety Issue?: No
• Spinal Cord Injury Measure
  • Time Frame: 2 years
    Safety Issue?: No
• CSF collection (6/day) and biochemical assays
  • Time Frame: 7 days
    Safety Issue?: No
• Sequential Anatomical MRI
  • Time Frame: 1 year
    Safety Issue?: No

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

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 16 Years

Maximum Age for this Clinical Trial: N/A

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: University of Calgary

Overall Clinical Trial Officials and Contacts

Steven Casha, MD PhD FRCSC Principal Investigator University of Calgary  

Overall Contact: Steven Casha, MD PhD 403 944 3405 scasha@ucalgary.ca

Information obtained from ClinicalTrials.gov on September 05, 2008

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00559494

Study ID Number: 17007

ClinicalTrials.gov Identifier: NCT00559494

Health Authority: Canada: Health Canada