Minocycline and Perfusion Pressure Augmentation in Acute Spinal Cord Injury
A Pilot Study to Assess Clinical Safety and Tolerance of Minocycline and Spinal Perfusion Pressure Augmentation in Acute Spinal Cord Injury
  • Phase

    Phase 1/Phase 2
  • Study Type

  • Status

    Completed No Results Posted
  • Intervention/Treatment

    minocycline ...
  • Study Participants

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.
Study Started
Jun 30
Primary Completion
Aug 31
Study Completion
Aug 31
Last Update
Mar 18

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 names: Minocin

Drug placebo

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

  • Other names: control, saline

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

Minocycline Experimental

Placebo Placebo Comparator

SCPP augmentation Experimental

SCPP control Sham Comparator


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
No Results Posted