Minocycline and Perfusion Pressure Augmentation in Acute Spinal Cord Injury

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.

Conditions

• Spinal Cord Injuries

Interventions

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)

DRUG

placebo

Normal saline 250cc via central line similar to minocycline arm administration protocol

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

Sponsors & Collaborators

• Paralyzed Veterans of America

  collaborator OTHER

• American Association of Neurological Surgeons

  collaborator OTHER

• Hotchkiss Brain Institute, University of Calgary

  collaborator OTHER

• University of Calgary

  lead OTHER

Principal Investigators

• Steven Casha, MD PhD FRCSC · University of Calgary

• R. John Hurlbert, MD PhD FRCSC · University of Calgary

• David Zygun, MD MSc · University of Calgary

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Model

PARALLEL

Eligibility

Min Age

16 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2004-06-30

Primary Completion

2010-08-31

Completion

2010-08-31

Countries

• Canada

Study Locations