Minocycline and Perfusion Pressure Augmentation in Acute Spinal Cord Injury

NCT00559494 | Completed Phase 1 DMC

• 2 other identifiers: 17007PVA2414
• Study Type: interventional
• Target: 52
• Locations: 1 country
• Sites: 1

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.

Conditions

Spinal Cord Injuries

Keywords

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

Outcome Measures

Primary Outcomes (1)

• Protocol compliance, feasibility and adverse events

  2 years

Secondary Outcomes (7)

• American Spinal Injury Association - motor score (primary clinical outcome) and sensory scores

  2 years

• Short Form 36 - Quality of Life Assessment

  2 years

• Functional Independence Measure

  2 years

• London Handicap Scale

  2 years

• Spinal Cord Injury Measure

  2 years

Study Arms (4)

Minocycline

EXPERIMENTAL

Drug: Minocycline

Placebo

PLACEBO COMPARATOR

Drug: placebo

SCPP augmentation

EXPERIMENTAL

Procedure: SCPP augmentation

SCPP control

SHAM COMPARATOR

Procedure: SCPP control

Interventions

Minocycline DRUG

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)

Also known as: Minocin

Minocycline

placebo DRUG

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

Also known as: control, saline

Placebo

SCPP augmentation PROCEDURE

maintenance of spinal cord perfusion pressure at 75 mmHg with fluids and inotrope protocol

SCPP augmentation

SCPP control PROCEDURE

maintenance of Mean arterial pressure of \>65 mmHg with fluids and inotropes protocol without spinal cord perfusion pressure as target or guiding therapy

SCPP control

Eligibility Criteria

• Age: 16 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Calgary: lead
• Paralyzed Veterans of America: collaborator
• American Association of Neurological Surgeons: collaborator
• Hotchkiss Brain Institute, University of Calgary: collaborator

Study Sites (1)

Foothills Medical Centre

Calgary, Alberta, T2N 2T9, Canada

Location

Related Publications (2)

• 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.

  PMID: 22505632 RESULT

• 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.

  PMID: 20418657 DERIVED

MeSH Terms

Conditions

Spinal Cord Injuries

Interventions

Minocycline; Sodium Chloride

Condition Hierarchy (Ancestors)

Spinal Cord Diseases; Central Nervous System Diseases; Nervous System Diseases; Trauma, Nervous System; Wounds and Injuries

Intervention Hierarchy (Ancestors)

Tetracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Sodium Compounds

Study Officials

• 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

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor

Study Record Dates

• First Submitted: November 14, 2007
• First Posted: November 16, 2007
• Study Start: June 1, 2004
• Primary Completion: August 1, 2010
• Study Completion: August 1, 2010
• Last Updated: March 18, 2013

Record last verified: 2013-03

Locations

CA (1)