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Minocycline and Perfusion Pressure Augmentation in Acute Spinal Cord Injury

Primary Purpose

Spinal Cord Injuries

Status
Completed
Phase
Phase 1
Locations
Canada
Study Type
Interventional
Intervention
Minocycline
placebo
SCPP augmentation
SCPP control
Sponsored by
University of Calgary
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Spinal Cord Injuries focused on measuring complete spinal cord injury, incomplete spinal cord injury, central cord spinal cord injury, traumatic

Eligibility Criteria

16 Years - undefined (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Foothills Medical Centre

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Experimental

Placebo Comparator

Experimental

Sham Comparator

Arm Label

Minocycline

Placebo

SCPP augmentation

SCPP control

Arm Description

Outcomes

Primary Outcome Measures

Protocol compliance, feasibility and adverse events

Secondary Outcome Measures

American Spinal Injury Association - motor score (primary clinical outcome) and sensory scores
Short Form 36 - Quality of Life Assessment
Functional Independence Measure
London Handicap Scale
Spinal Cord Injury Measure
CSF collection (6/day) and biochemical assays
Sequential Anatomical MRI

Full Information

First Posted
November 14, 2007
Last Updated
March 15, 2013
Sponsor
University of Calgary
Collaborators
Paralyzed Veterans of America, American Association of Neurological Surgeons, Hotchkiss Brain Institute, University of Calgary
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1. Study Identification

Unique Protocol Identification Number
NCT00559494
Brief Title
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

2. Study Status

Record Verification Date
March 2013
Overall Recruitment Status
Completed
Study Start Date
June 2004 (undefined)
Primary Completion Date
August 2010 (Actual)
Study Completion Date
August 2010 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University of Calgary
Collaborators
Paralyzed Veterans of America, American Association of Neurological Surgeons, Hotchkiss Brain Institute, University of Calgary

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Spinal Cord Injuries
Keywords
complete spinal cord injury, incomplete spinal cord injury, central cord spinal cord injury, traumatic

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
52 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Minocycline
Arm Type
Experimental
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Title
SCPP augmentation
Arm Type
Experimental
Arm Title
SCPP control
Arm Type
Sham Comparator
Intervention Type
Drug
Intervention Name(s)
Minocycline
Other Intervention Name(s)
Minocin
Intervention Description
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)
Intervention Type
Drug
Intervention Name(s)
placebo
Other Intervention Name(s)
control, saline
Intervention Description
Normal saline 250cc via central line similar to minocycline arm administration protocol
Intervention Type
Procedure
Intervention Name(s)
SCPP augmentation
Intervention Description
maintenance of spinal cord perfusion pressure at 75 mmHg with fluids and inotrope protocol
Intervention Type
Procedure
Intervention Name(s)
SCPP control
Intervention Description
maintenance of Mean arterial pressure of >65 mmHg with fluids and inotropes protocol without spinal cord perfusion pressure as target or guiding therapy
Primary Outcome Measure Information:
Title
Protocol compliance, feasibility and adverse events
Time Frame
2 years
Secondary Outcome Measure Information:
Title
American Spinal Injury Association - motor score (primary clinical outcome) and sensory scores
Time Frame
2 years
Title
Short Form 36 - Quality of Life Assessment
Time Frame
2 years
Title
Functional Independence Measure
Time Frame
2 years
Title
London Handicap Scale
Time Frame
2 years
Title
Spinal Cord Injury Measure
Time Frame
2 years
Title
CSF collection (6/day) and biochemical assays
Time Frame
7 days
Title
Sequential Anatomical MRI
Time Frame
1 year

10. Eligibility

Sex
All
Minimum Age & Unit of Time
16 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Steven Casha, MD PhD FRCSC
Organizational Affiliation
University of Calgary
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
R. John Hurlbert, MD PhD FRCSC
Organizational Affiliation
University of Calgary
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
David Zygun, MD MSc
Organizational Affiliation
University of Calgary
Official's Role
Principal Investigator
Facility Information:
Facility Name
Foothills Medical Centre
City
Calgary
State/Province
Alberta
ZIP/Postal Code
T2N 2T9
Country
Canada

12. IPD Sharing Statement

Citations:
PubMed Identifier
22505632
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.
Results Reference
result
PubMed Identifier
20418657
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.
Results Reference
derived

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Minocycline and Perfusion Pressure Augmentation in Acute Spinal Cord Injury

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