Spinal Cord Injury Neuroprotection With Glyburide (SCING)

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

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

Study Overview

• Status: Terminated
• Conditions: Acute Spinal Cord Injury
• Intervention / Treatment: Drug: Glyburide

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.

• Study Type: Interventional
• Enrollment (Actual): 3
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • Ohio
    • Columbus, Ohio, United States, 43210
      • The Ohio State University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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.	Drug: Glyburide; 3 day drug regimen beginning 8 hours after acute traumatic spinal cord injury.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Ohio State University
• Investigators: Principal Investigator: H. Francis Farhadi, MD, PhD, Ohio State University

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (Actual): February 14, 2017
• Primary Completion (Actual): February 8, 2021
• Study Completion (Actual): February 8, 2021

Study Registration Dates

• First Submitted: August 13, 2015
• First Submitted That Met QC Criteria: August 13, 2015
• First Posted (Estimate): August 14, 2015

Study Record Updates

• Last Update Posted (Actual): July 5, 2022
• Last Update Submitted That Met QC Criteria: June 7, 2022
• Last Verified: June 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Central Nervous System Diseases; Nervous System Diseases; Trauma, Nervous System; Spinal Cord Diseases; Wounds and Injuries; Spinal Cord Injuries; Hypoglycemic Agents; Physiological Effects of Drugs; Glyburide
• Other Study ID Numbers: 2014H0335

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No