SCING: Spinal Cord Injury Neuroprotection With Glyburide

• Sponsor: Ohio State University (Other)
• Overall Status: Terminated
• CT.gov ID: NCT02524379
• Collaborator: (none)
• Enrollment: 3
• Location: 1
• Arm: 1
• Actual Duration (Months): 47.8
• Patients Per Site Per Month: 0.1

Study Details

Study Description

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).

Condition or Disease	Intervention/Treatment	Phase
Acute Spinal Cord Injury	Drug: Glyburide	Phase 1/Phase 2

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 Design

• Study Type: Interventional
• Actual Enrollment: 3 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• 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
• Actual Study Start Date: Feb 14, 2017
• Actual Primary Completion Date: Feb 8, 2021
• Actual Study Completion Date: Feb 8, 2021

Arms and Interventions

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.

Outcome Measures

Primary Outcome Measures

1. 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.

2. 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 Outcome Measures

1. 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.

2. 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

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 80 Years
• Sexes Eligible for Study: All
• Accepts 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).

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	The Ohio State University	Columbus	Ohio	United States	43210

Sponsors and Collaborators

• Ohio State University

Investigators

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

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Feb 6, 2020
• Informed Consent Form - Dec 31, 2019

More Information

Publications

None provided.

• Responsible Party: Ohio State University
• ClinicalTrials.gov Identifier: NCT02524379
• Other Study ID Numbers: 2014H0335
• First Posted: Aug 14, 2015
• Last Update Posted: Jul 5, 2022
• Last Verified: Jun 1, 2022

• Individual Participant Data (IPD) Sharing Statement: Undecided
• Plan to Share IPD: Undecided
• 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
• Additional relevant MeSH terms: Spinal Cord Injuries; Wounds and Injuries; Glyburide

Study Results

Participant Flow

Arm/Group Title	Glyburide Treatment Arm
Arm/Group Description	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.
Period Title: Overall Study
STARTED	3
COMPLETED	2
NOT COMPLETED	1

Baseline Characteristics

Arm/Group Title	Glyburide Treatment Arm
Arm/Group Description	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.
Overall Participants	3
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	2 66.7%
>=65 years	1 33.3%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	57 (10.03)
Sex: Female, Male (Count of Participants)
Female	1 33.3%
Male	2 66.7%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%
Not Hispanic or Latino	3 100%
Unknown or Not Reported	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	0 0%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	0 0%
White	3 100%
More than one race	0 0%
Unknown or Not Reported	0 0%
Region of Enrollment (Count of Participants)
United States	3 100%

Outcome Measures

1. Primary Outcome

Title	Number of Participants With tSCI Recruited Within the Specified Time Window
Description	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)

Outcome Measure Data

Analysis Population Description

A total of 24 patients with acute cervical tSCI were screened over the course of the study for eligibility.

Arm/Group Title	Glyburide Treatment Arm
Arm/Group Description	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.
Measure Participants	24
Count of Participants [Participants]	3 100%

2. Primary Outcome

Title	Number of Drug Related Adverse Events
Description	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Glyburide Treatment Arm
Arm/Group Description	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.
Measure Participants	3
Number [Events]	0

3. Secondary Outcome

Title	Number of Participants With Neurologic Recovery Following tSCI
Description	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Glyburide Treatment Arm
Arm/Group Description	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.
Measure Participants	2
Count of Participants [Participants]	2 66.7%

4. Secondary Outcome

Title	Serum Pharmacokinetic and Biomarker Analysis
Description	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

Outcome Measure Data

Analysis Population Description

Principal Investigator left university: Samples were not analyzed at study termination.

Arm/Group Title	Glyburide Treatment Arm
Arm/Group Description	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.
Measure Participants	0

Adverse Events

Time Frame	1 year
Arm/Group Title	Glyburide Treatment Arm
Arm/Group Description	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.
All Cause Mortality
	Glyburide Treatment Arm
	Affected / at Risk (%)	# Events
Total	1/3 (33.3%)
Serious Adverse Events
	Glyburide Treatment Arm
	Affected / at Risk (%)	# Events
Total	2/3 (66.7%)
Cardiac disorders
Bradycardia	1/3 (33.3%)	1
Other Dysrhythmia (Tachy-brady syndrome)	1/3 (33.3%)	1
Gastrointestinal disorders
Acute Renal Failure	1/3 (33.3%)	1
Respiratory, thoracic and mediastinal disorders
Acute respiratory distress syndrome (ARDS) - Atelecetasis	1/3 (33.3%)	1
Other (Not Including Serious) Adverse Events
	Glyburide Treatment Arm
	Affected / at Risk (%)	# Events
Total	1/3 (33.3%)
Blood and lymphatic system disorders
Thromocytopenia	1/3 (33.3%)	1
Anemia	1/3 (33.3%)	1
Infections and infestations
Urinary Tract Infection (UTI)	1/3 (33.3%)	1
Metabolism and nutrition disorders
Hypoglycemia	1/3 (33.3%)	1

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.