Minocycline and Perfusion Pressure Augmentation in Acute Spinal Cord Injury

Condition(s) targeted: Spinal Cord Injuries

Intervention: Minocycline (Drug); placebo (Drug); SCPP augmentation (Procedure); SCPP control (Procedure)

Phase: Phase 1/Phase 2

Status: Recruiting

Sponsored by: University of Calgary

Official(s) and/or principal investigator(s):
Steven Casha, MD PhD FRCSC, Principal Investigator, Affiliation: University of Calgary
R. John Hurlbert, MD PhD FRCSC, Principal Investigator, Affiliation: University of Calgary
David Zygun, MD MSc, Principal Investigator, Affiliation: University of Calgary

Overall contact:
Steven Casha, MD PhD, Phone: 403 944 3405, Email: scasha@ucalgary.ca

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.

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

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

Primary outcome: Protocol compliance, feasibility and adverse events

Secondary outcome:

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

Minimum age: 16 Years. Maximum age: N/A. Gender(s): Both.

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

Steven Casha, MD PhD, Phone: 403 944 3405, Email: scasha@ucalgary.ca

Foothills Medical Centre, Calgary, Alberta T2N 2T9, Canada; Recruiting
Steven Casha, MD PhD FRCSC, Phone: 403 944 3405, Email: scasha@ucalgary.ca
Steven Casha, MD PhD FRCSC, Principal Investigator

Starting date: June 2004
Ending date: November 2010
Last updated: June 4, 2008