Minocycline and Perfusion Pressure Augmentation in Acute Spinal Cord Injury

This study has been completed.
Sponsor:
Collaborators:
Paralyzed Veterans of America
American Association of Neurological Surgeons
Hotchkiss Brain Institute, University of Calgary
Information provided by (Responsible Party):
Steve Casha, University of Calgary
ClinicalTrials.gov Identifier:
NCT00559494
First received: November 14, 2007
Last updated: March 15, 2013
Last verified: March 2013

November 14, 2007
March 15, 2013
June 2004
August 2010   (final data collection date for primary outcome measure)
Protocol compliance, feasibility and adverse events [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
Protocol compliance, feasibility and adverse events [ Time Frame: 2 years ]
Complete list of historical versions of study NCT00559494 on ClinicalTrials.gov Archive Site
  • American Spinal Injury Association - motor score (primary clinical outcome) and sensory scores [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  • Short Form 36 - Quality of Life Assessment [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  • Functional Independence Measure [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  • London Handicap Scale [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  • Spinal Cord Injury Measure [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  • CSF collection (6/day) and biochemical assays [ Time Frame: 7 days ] [ Designated as safety issue: No ]
  • Sequential Anatomical MRI [ Time Frame: 1 year ] [ Designated as safety issue: No ]
  • American Spinal Injury Association - motor score (primary clinical outcome) and sensory scores [ Time Frame: 2 years ]
  • Short Form 36 - Quality of Life Assessment [ Time Frame: 2 years ]
  • Functional Independence Measure [ Time Frame: 2 years ]
  • London Handicap Scale [ Time Frame: 2 years ]
  • Spinal Cord Injury Measure [ Time Frame: 2 years ]
  • CSF collection (6/day) and biochemical assays [ Time Frame: 7 days ]
  • Sequential Anatomical MRI [ Time Frame: 1 year ]
Not Provided
Not Provided
 
Minocycline and Perfusion Pressure Augmentation in Acute Spinal Cord Injury
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.

Not Provided
Interventional
Phase 1
Phase 2
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Spinal Cord Injuries
  • 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)
    Other Name: Minocin
  • Drug: placebo
    Normal saline 250cc via central line similar to minocycline arm administration protocol
    Other Names:
    • control
    • saline
  • 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
  • Experimental: Minocycline
    Intervention: Drug: Minocycline
  • Placebo Comparator: Placebo
    Intervention: Drug: placebo
  • Experimental: SCPP augmentation
    Intervention: Procedure: SCPP augmentation
  • Sham Comparator: SCPP control
    Intervention: Procedure: SCPP control

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
52
August 2010
August 2010   (final data collection date for primary outcome measure)

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
Both
16 Years and older
No
Contact information is only displayed when the study is recruiting subjects
Canada
 
NCT00559494
17007, PVA2414
Yes
Steve Casha, University of Calgary
University of Calgary
  • Paralyzed Veterans of America
  • American Association of Neurological Surgeons
  • Hotchkiss Brain Institute, University of Calgary
Principal Investigator: Steven Casha, MD PhD FRCSC University of Calgary
Principal Investigator: R. John Hurlbert, MD PhD FRCSC University of Calgary
Principal Investigator: David Zygun, MD MSc University of Calgary
University of Calgary
March 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP