Spinal Cord Injury Neuroprotection With Glyburide

Study Overview
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Brief Summary
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The purpose of this study is to determine the safety of using oral Glyburide in patients with acute traumatic cervical spinal cord injuries (SCI).

Detailed Description
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This study will include patients between 18 and 80 years who have experienced acute traumatic cervical spinal cord injury (specifically ASIA A, B or C). Patients will then begin an oral drug regimen of Glyburide, which must be started within 8 hours of injury and continued for 72 hours at a daily dose of 3.125 mg on Day 1, 2.5 mg on Day 2 and 2.5 mg on Day 3. If indicated, the patient will also have surgical intervention for spinal cord decompression and spinal stabilization. Each patient who takes part in this study will have labs drawn regularly and adverse events assessed daily through Day 14 or 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; 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


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age: ≥ 18 years and ≤ 80 years Written informed consent by patient or legal authorized representative No other life-threatening injury No evidence of sepsis Acute cervical SCI with ASIA Impairment Scale grade A, B or C on admission Non-penetrating SCI at neurologic level from C2 to C8 Initiation of study drug within 8 hours of injury 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 Other illness (including mental disorder) that could preclude accurate medical and neurological evaluation (at discretion of the site investigator) Unable to commit to the follow-up schedule A recent history of regular substance abuse (illicit drugs, alcohol), which in the opinion of the investigator would interfere with the subject's participation in the study Any condition likely to result in the patient's death within the next 12 months Prisoner 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 > 2 times upper limit normal. Subjects may be randomized if liver function tests have been drawn but are not yet available and the subject has no known history of liver disease; however, treatment with DiaBeta will be discontinued prior to the second dose if liver function tests indicate ALT > 3 times upper limit of normal or bilirubin > 2 times upper limit of normal 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 treatment with Bosentan within past 7 days Known G6PD enzyme deficiency Pregnancy: Women must be either post-menopausal, permanently sterilized or, if ≤ 50 years old, must have a negative test for pregnancy obtained before enrollment Breast-feeding women who do not agree to stop breast-feeding during and for 7 days following the end of oral glyburide administration Subjects who in the opinion of the investigator are not suitable for inclusion in the study (reason to be documented).

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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No

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>Enrolled patients will receive 12 doses of Glyburide starting within 8 hours of SCI. The dosing regimen involves an initial dose of 1.25 mg followed by eleven 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. | Drug: Glyburide<br>* 3 day drug regimen beginning 8 hours after acute traumatic spinal cord injury.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With tSCI Recruited Within the Specified Time Window | A measure of feasibility of undertaking a larger phase II study among this population of patients where treatment must begin within a short injury-to-drug time window. | Enrollment Period (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 within a short injury-to-drug time window. | One year post enrollment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Neurologic Recovery Following tSCI | The neurologic status of patients will be assessed using the American Spinal Injury Association (ASIA) Impairment Scale (AIS) as assessed by International Standards for Neurological Classification of SCI (ISNCSCI) criteria. | One year post enrollment | 
| Serum Pharmacokinetic and Biomarker Analysis | Plasma concentrations will be serially quantified through day 3 following tSCI to evaluate the pharmacokinetics of Glyburide in the acute tSCI population. Comparisons will be made to reported levels achieved in healthy patient cohorts. 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 through post-treatment day 7 |