Acute Spinal Cord Injury
Conditions
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.
Interventions
DRUGGlyburide
3 day drug regimen beginning 8 hours after acute traumatic spinal cord injury.
Sponsors
Ohio State University
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
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).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With tSCI Recruited Within the Specified Time Window | Enrollment Period (within 8 hours of tSCI) | 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. |
| Number of Drug Related Adverse Events | One year post enrollment | A measure of safety of treating patients with traumatic spinal cord injury with Glyburide administered orally within a short injury-to-drug time window. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Neurologic Recovery Following tSCI | One year post enrollment | 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. |
| Serum Pharmacokinetic and Biomarker Analysis | Enrollment through post-treatment day 7 | 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 |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Glyburide Treatment Arm 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.
Glyburide: 3 day drug regimen beginning 8 hours after acute traumatic spinal cord injury. | 3 |
| Total | 3 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Death | 1 |
Baseline characteristics
| Characteristic | Glyburide Treatment Arm |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 1 Participants |
| Age, Categorical Between 18 and 65 years | 2 Participants |
| Age, Continuous | 57 years STANDARD_DEVIATION 10.03 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 3 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 3 Participants |
| Region of Enrollment United States | 3 Participants |
| Sex: Female, Male Female | 1 Participants |
| Sex: Female, Male Male | 2 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 1 / 3 |
| other Total, other adverse events | 1 / 3 |
| serious Total, serious adverse events | 2 / 3 |
Outcome results
Primary
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.
Time frame: One year post enrollment
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Glyburide Treatment Arm | Number of Drug Related Adverse Events | 0 Events |
Primary
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.
Time frame: Enrollment Period (within 8 hours of tSCI)
Population: A total of 24 patients with acute cervical tSCI were screened over the course of the study for eligibility.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Glyburide Treatment Arm | Number of Participants With tSCI Recruited Within the Specified Time Window | 3 Participants |
Secondary
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.
Time frame: One year post enrollment
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Glyburide Treatment Arm | Number of Participants With Neurologic Recovery Following tSCI | 2 Participants |
Secondary
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
Time frame: Enrollment through post-treatment day 7
Population: Principal Investigator left university: Samples were not analyzed at study termination.