Clinical trial NCT02524379: Spinal Cord Injury Neuroprotection With Glyburide
Official title: 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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
PHASE2
Conditions: Acute Spinal Cord Injury
Lead sponsor: Ohio State University
Sponsor class: OTHER
First posted: 2015-08-14
Enrollment: 3
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: Inclusion Criteria:

1. Age: ≥ 18 years and ≤ 80 years
2. Written informed consent by patient or legal authorized representative
3. No other life-threatening injury
4. No evidence of sepsis
5. Acute cervical SCI with ASIA Impairment Scale grade A, B or C on admission
6. Non-penetrating SCI at neurologic level from C2 to C8
7. Initiation of study drug within 8 hours of injury

Exclusion Criteria

1. Unconsciousness or other mental impairment that prevents neurological assessment within the first 8 hours
2. Acute SCI with ASIA Impairment Scale grade D or E
3. Currently involved in another non-observational SCI research study or receiving another investigational drug
4. History of hypersensitivity to sulfonylureas, in particular glyburide, or any of its components
5. Other illness (including mental disorder) that could preclude accurate medical and neurological evaluation (at discretion of the site investigator)
6. Unable to commit to the follow-up schedule
7. 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
8. Any condition likely to result in the patient's death within the next 12 months
9. Prisoner
10. Severe renal disorder from the patient's history (e.g. dialysis) or baseline eGFR of \< 30 mL/min/1.73 m2
11. 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
12. Blood glucose \<55 mg/dL at enrollment or immediately prior to administration of DiaBeta, or a clinically significant history of hypoglycemia
13. 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
14. Known treatment with Bosentan within past 7 days
15. Known G6PD enzyme deficiency
16. Pregnancy: Women must be either post-menopausal, permanently sterilized or, if ≤ 50 years old, must have a negative test for pregnancy obtained before enrollment
17. Breast-feeding women who do not agree to stop breast-feeding during and for 7 days following the end of oral glyburide administration
18. Subjects who in the opinion of the investigator are not suitable for inclusion in the study (reason to be documented).

Primary outcomes:
measure: Number of Participants With tSCI Recruited Within the Specified Time Window
timeFrame: Enrollment Period (within 8 hours of tSCI)
measure: Number of Drug Related Adverse Events
timeFrame: One year post enrollment
Secondary outcomes:
measure: Number of Participants With Neurologic Recovery Following tSCI
timeFrame: One year post enrollment
measure: Serum Pharmacokinetic and Biomarker Analysis
timeFrame: Enrollment through post-treatment day 7
Other outcomes:
Locations:
city: Columbus
country: United States
facility: The Ohio State University
state: Ohio
Study officials:
affiliation: Ohio State University
name: H. Francis Farhadi, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Minnema AJ, Mehta A, Boling WW, Schwab J, Simard JM, Farhadi HF. SCING-Spinal Cord Injury Neuroprotection with Glyburide: a pilot, open-label, multicentre, prospective evaluation of oral glyburide in patients with acute traumatic spinal cord injury in the USA. BMJ Open. 2019 Oct 10;9(10):e031329. doi: 10.1136/bmjopen-2019-031329.