Spinal Cord Injury Neuroprotection With Glyburide

Study Overview
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Brief Summary
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To assess the safety and efficacy of using oral Glyburide (Diabeta) as a neuroprotective agent in patients with acute cervical or thoracic traumatic spinal cord injury.

Detailed Description
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This study will include subjects between 18 and 80 years who have experienced acute traumatic cervical or thoracic spinal cord injury. Subjects will begin an oral drug regimen of Glyburide with the initial dose being within 8 hours of the injury and again every 6 hours after for 72 total hours of treatment. The daily dose of 3.125mg on day one and 2.5 mg on days 2 and 3 will be used to determine if the investigational drug provides any neuroprotection when given soon after injury. If indicated, the subject will also have surgical intervention for spinal cord decompression surgery and spinal stabilization. Participants will have labs drawn regularly, and ECGs done throughout their hospital stay. Adverse events will be monitored daily through day 14 of participation or hospital discharge (whichever is earlier). Study participation will last for 365 days (+/- 30 days), with post-hospitalization follow-up occurring on days 28, 42, 84, 182, and 365.

Official Title
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Spinal Cord Injury Neuroprotection With Glyburide (SCING): Pilot Study: An Open-Label Prospective Evaluation of the Feasibility, Safety, Pharmacokinetics, and Preliminary Efficacy of Oral Glyburide (DiaBeta) in Patients With Acute Traumatic Spinal Cord Injury

Conditions
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Acute Spinal Cord Injury

Intervention / Treatment
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* Drug: GlyBURIDE Oral Tablet


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: No life threatening injuries resulting from the traumatic accident No evidence of sepsis Acute cervical or thoracic SCI with ASIA Impairment Scale Grade A, B, or C od admission. Non-penetrating SCI at neurologic level from C2 to C8 or T1 to T12 Exclusion Criteria: Unconsciousness or other mental impairment that prevents neurological assessment within the first 8 hours Acute SCI with ASIA Impairment Scale grade D or E Currently involved in another non-observational SCI research study or receiving another investigational drug History of hypersensitivity to sulfonylureas, in particular glyburide, or any of its components Any condition likely to result in the patient's death within the next 12 months Severe renal disorder from the patient's history (e.g. dialysis) or baseline eGFR of < 30 mL/min/1.73 m2 Known severe liver disease, or ALT > 3 times upper limit of normal or bilirubin Blood glucose <55 mg/dL at enrollment or immediately prior to administration of DiaBeta, or a clinically significant history of hypoglycemia Acute ST elevation myocardial infarction, and/or acute decompensated heart failure, and/or QTc > 520 ms, and/or known history of cardiac arrest (PEA, VT, VF, asystole), and/or admission for an acute coronary syndrome, myocardial infarction, or coronary intervention (percutaneous coronary intervention or coronary artery surgery) within the past 3 months Known G6PD enzyme deficiency

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Glyburide treatment arm<br> | Drug: GlyBURIDE Oral Tablet<br>* Enrolled patients will receive 12 doses of Glyburide starting within 8 hours of spinal cord injury. The dosing regimen involves an initial dose of 1.25mg followed by 11 consecutive doses of 0.625 mg every 6 hours. The total daily dose of Glyburide on Day 1, Day 2, and Day 3 will be 3.125 mg, 2.5 mg, and 2.5 mg respectively. Intervention: Drug: Glyburide<br>* Other names: Diabeta;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate of recruitment of patients with tSCI within the specified time window. | A measure of feasibility of undertaking a large phase II study among this population of patients where treatment must begin within a short injury-to-drug time window. | within 8 hours of tSCI | 
| Number of drug related adverse events. | A measure of safety of treating patients with traumatic spinal cord injury with Glyburide administered orally. | One year post treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Neurologic recovery following tSCI | Neurologic status be assessed using the American Spinal Injury Association Impairment Scale. This neurological exam assesses sensory and motor impairments using touch and pin prick evaluations in each dermatome and muscle strength. Right and left body sides are evaluated independently. Lower the scores indicate greater degree of impairment. Touch and pin prick perception is scored using a 0-2 and NT grade. Where 0= Absent, 1= hypo/hypersensitivity, 2= normal sensation, and NT= not testable. Scores for each body side are added together and summed for a total sensation score. Maximum score possible for this section is 112 per side. Muscle function is rated on a 0-5 scale. Where 0= total paralysis, 1= palpable/visible contraction, 2= active movement, full ROM with gravity eliminated, 3= active movement, full ROM against gravity, 4= active movement, full ROM with moderate resistance, 5= Normal movement and strength, and NT= not tested. Maximum score for this section is 50 per side. | One year post enrollment. | 
| Serum Pharmacokinetics to measure Glyburide concentrations. | Plasma concentrations of Glyburide will be serially quantified through day 3 following tSCI to evaluate the pharmacokinetics of the investigational drug. Comparisons will be made to reported levels achieved in healthy patient cohorts. | Enrollment through post-treatment day 7. | 
| Biomarker Analysis | Standard enzyme-linked immunosorbent assay (ELISA) techniques will be used to measure blood levels of neurofilament light chain, neuron- specific enolase, tau, S100b, and glial fibrillary acidic protein levels on admission, at 24 hours and on days 3 and 7 following tSCI to evaluate serum biomarker levels. Comparisons will be made to previously published values observed in non-treated control patients | Enrollment, Day 3, and Day 7 |