Minocycline and Perfusion Pressure Augmentation in Acute Spinal Cord Injury

Study Description

Go to 

Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

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.

Condition or disease	Intervention/treatment	Phase
Spinal Cord Injuries	Drug: Minocycline; Drug: placebo; Procedure: SCPP augmentation; Procedure: SCPP control	Phase 1; Phase 2

Study Design

Go to 

Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Study Type :	Interventional (Clinical Trial)
Actual Enrollment :	52 participants
Allocation:	Randomized
Intervention Model:	Parallel Assignment
Masking:	Quadruple (Participant, Care Provider, 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
Study Start Date :	June 2004
Actual Primary Completion Date :	August 2010
Actual Study Completion Date :	August 2010

Arms and Interventions

Go to 

Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Arm	Intervention/treatment
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

Outcome Measures

Go to 

Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Primary Outcome Measures :

1. Protocol compliance, feasibility and adverse events [ Time Frame: 2 years ]

Secondary Outcome Measures :

1. American Spinal Injury Association - motor score (primary clinical outcome) and sensory scores [ Time Frame: 2 years ]
2. Short Form 36 - Quality of Life Assessment [ Time Frame: 2 years ]
3. Functional Independence Measure [ Time Frame: 2 years ]
4. London Handicap Scale [ Time Frame: 2 years ]
5. Spinal Cord Injury Measure [ Time Frame: 2 years ]
6. CSF collection (6/day) and biochemical assays [ Time Frame: 7 days ]
7. Sequential Anatomical MRI [ Time Frame: 1 year ]

Eligibility Criteria

Go to 

Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Ages Eligible for Study:	16 Years and older (Child, Adult, Senior)
Sexes Eligible for Study:	All
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

Go to 

Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

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

Go to 

Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Publications of Results:

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.

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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. Epub 2010 Apr 10.

Responsible Party:	Steve Casha, Assistant Professor, University of Calgary
ClinicalTrials.gov Identifier:	NCT00559494 History of Changes
Other Study ID Numbers:	17007; PVA2414 ( Other Grant/Funding Number: Paralyzed Veterans of America )
First Posted:	November 16, 2007
Last Update Posted:	March 18, 2013
Last Verified:	March 2013

Keywords provided by Steve Casha, University of Calgary:

complete spinal cord injury; incomplete spinal cord injury; central cord spinal cord injury; traumatic

Additional relevant MeSH terms:

Wounds and Injuries; Spinal Cord Injuries; Spinal Cord Diseases; Central Nervous System Diseases; Nervous System Diseases	Trauma, Nervous System; Minocycline; Anti-Bacterial Agents; Anti-Infective Agents