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
  Purpose

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.


Condition Intervention Phase
Spinal Cord Injuries
Drug: Minocycline
Drug: placebo
Procedure: SCPP augmentation
Procedure: SCPP control
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Pilot Study to Assess Clinical Safety and Tolerance of Minocycline and Spinal Perfusion Pressure Augmentation in Acute Spinal Cord Injury

Resource links provided by NLM:


Further study details as provided by University of Calgary:

Primary Outcome Measures:
  • Protocol compliance, feasibility and adverse events [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • 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 ]

Enrollment: 52
Study Start Date: June 2004
Study Completion Date: August 2010
Primary Completion Date: August 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Minocycline 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
Placebo Comparator: Placebo Drug: placebo
Normal saline 250cc via central line similar to minocycline arm administration protocol
Other Names:
  • control
  • saline
Experimental: SCPP augmentation Procedure: SCPP augmentation
maintenance of spinal cord perfusion pressure at 75 mmHg with fluids and inotrope protocol
Sham Comparator: SCPP control 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

  Eligibility

Ages Eligible for Study:   16 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00559494

Locations
Canada, Alberta
Foothills Medical Centre
Calgary, Alberta, Canada, T2N 2T9
Sponsors and Collaborators
University of Calgary
Paralyzed Veterans of America
American Association of Neurological Surgeons
Hotchkiss Brain Institute, University of Calgary
Investigators
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
  More Information

Publications:
Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Steve Casha, Assistant Professor, University of Calgary
ClinicalTrials.gov Identifier: NCT00559494     History of Changes
Other Study ID Numbers: 17007, PVA2414
Study First Received: November 14, 2007
Last Updated: March 15, 2013
Health Authority: Canada: Health Canada

Keywords provided by University of Calgary:
complete spinal cord injury
incomplete spinal cord injury
central cord spinal cord injury
traumatic

Additional relevant MeSH terms:
Spinal Cord Injuries
Wounds and Injuries
Spinal Cord Diseases
Central Nervous System Diseases
Nervous System Diseases
Trauma, Nervous System
Minocycline
Anti-Bacterial Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on April 17, 2014