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| ID | Type | Description | Link |
|---|---|---|---|
| PVA2414 | Other Grant/Funding Number | Paralyzed Veterans of America |
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| Name | Class |
|---|---|
| Paralyzed Veterans of America | OTHER |
| American Association of Neurological Surgeons | OTHER |
| Hotchkiss Brain Institute, University of Calgary | OTHER |
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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Minocycline | Experimental |
| |
| Placebo | Placebo Comparator |
| |
| SCPP augmentation | Experimental |
| |
| SCPP control | Sham Comparator |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| 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) |
| Measure | Description | Time Frame |
|---|---|---|
| Protocol compliance, feasibility and adverse events | 2 years |
| Measure | Description | Time Frame |
|---|---|---|
| American Spinal Injury Association - motor score (primary clinical outcome) and sensory scores | 2 years | |
| Short Form 36 - Quality of Life Assessment | 2 years | |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| 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 |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Foothills Medical Centre | Calgary | Alberta | T2N 2T9 | Canada |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 22505632 | Result | 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. | |
| 20418657 | Derived | 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. |
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| ID | Term |
|---|---|
| D013119 | Spinal Cord Injuries |
| ID | Term |
|---|---|
| D013118 | Spinal Cord Diseases |
| D002493 | Central Nervous System Diseases |
| D009422 | Nervous System Diseases |
| D020196 | Trauma, Nervous System |
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| ID | Term |
|---|---|
| D008911 | Minocycline |
| D012965 | Sodium Chloride |
| ID | Term |
|---|---|
| D013754 | Tetracyclines |
| D009279 | Naphthacenes |
| D011084 | Polycyclic Aromatic Hydrocarbons |
| D006841 | Hydrocarbons, Aromatic |
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|
| placebo | Drug | Normal saline 250cc via central line similar to minocycline arm administration protocol |
|
|
| SCPP augmentation | Procedure | maintenance of spinal cord perfusion pressure at 75 mmHg with fluids and inotrope protocol |
|
| 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 |
|
| Functional Independence Measure |
| 2 years |
| London Handicap Scale | 2 years |
| Spinal Cord Injury Measure | 2 years |
| CSF collection (6/day) and biochemical assays | 7 days |
| Sequential Anatomical MRI | 1 year |
| D014947 | Wounds and Injuries |
| D006844 |
| Hydrocarbons, Cyclic |
| D006838 | Hydrocarbons |
| D009930 | Organic Chemicals |
| D011083 | Polycyclic Compounds |
| D002712 | Chlorides |
| D006851 | Hydrochloric Acid |
| D017606 | Chlorine Compounds |
| D007287 | Inorganic Chemicals |
| D017670 | Sodium Compounds |