Glyburide for Spinal Cord Injury

(SCING Trial)

Overseen By Jaimie L Hixson, BS

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: University of Kentucky

Must not be taking: Sulfonylureas

Disqualifiers: Severe renal disorder, Liver disease, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 28

Duration: 3 days

12 Participants Needed

Trial Summary

What is the purpose of this trial?

To assess the safety and efficacy of using oral Glyburide (Diabeta) as a neuroprotective agent in patients with acute cervical or thoracic traumatic spinal cord injury.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. However, if you are currently involved in another non-observational spinal cord injury research study or receiving another investigational drug, you would not be eligible to participate.

What evidence supports the effectiveness of the drug glyburide for spinal cord injury?

Research in rats with spinal cord injury showed that glyburide helped reduce damage and improve recovery, with better outcomes in movement and weight gain compared to other treatments. This suggests glyburide might be effective in treating spinal cord injuries. ^{1 2 3 4 5}

How is the drug glyburide unique for treating spinal cord injury?

Glyburide is unique for treating spinal cord injury because it targets specific channels in the nervous system that are involved in swelling and damage after injury. This drug, originally used for diabetes, is being repurposed to reduce harmful swelling in the brain and potentially the spinal cord, which is different from other treatments that may not address these specific channels. ^{1 5 6 7 8}

Eligibility Criteria

This trial is for adults with recent non-penetrating spinal cord injuries at certain levels, who are not in immediate life-threatening condition and can undergo neurological assessment within 8 hours. Excluded are those with severe heart issues, other major health problems like liver or kidney disease, low blood glucose levels, or a known allergy to sulfonylureas.

Inclusion Criteria

I do not have sepsis.

My spinal cord injury is between my neck and mid-back without piercing the cord.

My spinal cord injury is severe but not complete, affecting my neck or upper back.

Exclusion Criteria

Currently involved in another non-observational SCI research study or receiving another investigational drug

I have severe kidney issues or am on dialysis.

I do not have severe liver disease or significantly high liver enzyme levels.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

within 8 hours

Treatment

Participants receive oral Glyburide starting within 8 hours of injury, every 6 hours for 72 hours

3 days

Continuous monitoring during hospital stay

Hospital Monitoring

Participants are monitored for adverse events and undergo regular lab tests and ECGs

up to 14 days or until hospital discharge

Follow-up

Participants are monitored for safety and effectiveness after treatment

365 days

Follow-up visits on days 28, 42, 84, 182, and 365

Treatment Details

Interventions

• Glyburide

Trial Overview The study tests if Glyburide (Diabeta), an oral tablet commonly used for diabetes, can protect the nerves after acute traumatic injury to the cervical or thoracic spine. The goal is to see if it's safe and effective in improving outcomes for these patients.

Participant Groups

Group I: Glyburide treatment arm Experimental Treatment 1 Intervention

Glyburide is already approved in United States, Canada, European Union for the following indications:

Approved in United States as Diabeta for:

• Type 2 diabetes mellitus

Approved in Canada as Euglucon for:

• Type 2 diabetes mellitus

Approved in European Union as Glyburide for:

• Type 2 diabetes mellitus

Who Is Running the Clinical Trial?

University of Kentucky

Lead Sponsor

Trials

198

Recruited

224,000+

Findings from Research

This study is a randomized, double-blind, placebo-controlled trial involving 306 patients with acute ischemic stroke, investigating the safety and efficacy of glibenclamide when combined with rtPA, a common treatment for stroke.

The primary goal is to determine if glibenclamide can improve outcomes at 90 days, while also monitoring safety through measures like 30-day mortality and serious adverse events, which will help assess its potential benefits for stroke patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and efficacy of glibenclamide combined with rtPA in acute cerebral ischemia with occlusion/stenosis of anterior circulation (SE-GRACE): study protocol for a randomized controlled trial. Huang, K., Ji, Z., Wu, Y., et al.[2020]

A study involving 24 healthy Mexican volunteers found that the two formulations of glyburide, Daonil and Gen-Glybe, have similar bioavailability, indicating they can be used interchangeably in treating type II diabetes.

The pharmacokinetic analysis showed that key parameters like maximum concentration (Cmax) and area under the curve (AUC24h) for both formulations fell within acceptable limits, confirming their bioequivalence.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bioequivalence of two oral formulations of glyburide (glibenclamide). Flores-Murrieta, FJ., Carrasco-Portugal, Mdel C., Reyes-García, G., et al.[2013]

Glyburide (GLY) effectively lowers blood glucose levels in diabetic rats and restores the activity of important antioxidant enzymes, superoxide dismutase (SOD) and catalase (CAT), in the brain after 4 weeks of treatment.

The study suggests that GLY not only stimulates insulin secretion but also has beneficial effects on brain antioxidant enzyme activities, which may help maintain blood glucose homeostasis in type 2 diabetes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The effects of sulfonylurea glyburide on superoxide dismutase, catalase, and glutathione peroxidase activities in the brain tissue of streptozotocin-induced diabetic rat. Nazaroglu, NK., Sepici-Dincel, A., Altan, N.[2013]

In a study comparing three treatments for reducing lesion expansion after spinal cord injury, systemic hypothermia and glibenclamide showed superior safety and efficacy compared to riluzole, with no treatment-related mortality in the glibenclamide group.

Both hypothermia and glibenclamide led to better locomotor recovery and less lesion volume compared to controls, while riluzole initially underperformed but caught up in the later stages of recovery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Direct Comparison of Three Clinically Relevant Treatments in a Rat Model of Cervical Spinal Cord Injury. Hosier, H., Peterson, D., Tsymbalyuk, O., et al.[2022]

The combination of glibenclamide and metformin effectively improves glycemic control in patients with type 2 diabetes, leading to better fasting plasma glucose and HbA1C levels, with a higher likelihood of achieving HbA1C < 7%.

While this combination therapy reduces the number of pills needed and addresses diabetes through different mechanisms, it carries risks of hypoglycemia and potential lactic acidosis, especially in elderly patients or those with renal issues.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Combination of glibenclamide-metformin HCl for the treatment of type 2 diabetes mellitus. Lamos, EM., Stein, SA., Davis, SN.[2021]

In a study involving diabetic rats, a four-week treatment with glyburide (5 mg/kg) significantly increased muscle superoxide dismutase (SOD) activity and lowered blood glucose levels.

The findings suggest that glyburide, a sulfonylurea medication, has direct insulin-like effects on muscle SOD activity, indicating its potential role in managing oxidative stress in diabetes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of the sulfonylurea glyburide on superoxide dismutase in streptozotocin-induced diabetic rat muscle. Altan, N., Yiğit, S., Elmali, E., et al.[2019]

Glyburide, traditionally used for diabetes, has been repurposed to target SUR1-TRPM4 channels in the brain, showing promise in reducing brain swelling and mortality in stroke patients, particularly in large hemispheric infarctions.

The GAMES clinical trials demonstrated that intravenous glyburide treatment led to significant improvements in brain swelling, functional outcomes, and reduced levels of MMP-9, indicating its potential as an effective intervention in acute central nervous system injuries.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Profile of intravenous glyburide for the prevention of cerebral edema following large hemispheric infarction: evidence to date. King, ZA., Sheth, KN., Kimberly, WT., et al.[2019]

Pregabalin pre-treatment significantly reduced spinal cord ischemia-reperfusion injury in rats, showing better outcomes in terms of ultrastructural and histopathological results compared to methylprednisolone (MP).

Both pregabalin and MP treatments demonstrated neuroprotective effects by lowering apoptosis and inflammatory markers, but pregabalin led to superior neurological recovery as measured by the BBB scoring system.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neuroprotective Effects of Pregabalin Against Spinal Cord Ischemia-Reperfusion Injury in Rats. Kazanci, B., Ozdogan, S., Kahveci, R., et al.[2018]

References

1. England pubmed.ncbi.nlm.nih.gov

Safety and efficacy of glibenclamide combined with rtPA in acute cerebral ischemia with occlusion/stenosis of anterior circulation (SE-GRACE): study protocol for a randomized controlled trial. [2020]

2. United States pubmed.ncbi.nlm.nih.gov

Bioequivalence of two oral formulations of glyburide (glibenclamide). [2013]

3. United States pubmed.ncbi.nlm.nih.gov

The effects of sulfonylurea glyburide on superoxide dismutase, catalase, and glutathione peroxidase activities in the brain tissue of streptozotocin-induced diabetic rat. [2013]

4. United States pubmed.ncbi.nlm.nih.gov

A Direct Comparison of Three Clinically Relevant Treatments in a Rat Model of Cervical Spinal Cord Injury. [2022]

5. England pubmed.ncbi.nlm.nih.gov

Combination of glibenclamide-metformin HCl for the treatment of type 2 diabetes mellitus. [2021]

6. England pubmed.ncbi.nlm.nih.gov

Effect of the sulfonylurea glyburide on superoxide dismutase in streptozotocin-induced diabetic rat muscle. [2019]

7. New Zealand pubmed.ncbi.nlm.nih.gov

Profile of intravenous glyburide for the prevention of cerebral edema following large hemispheric infarction: evidence to date. [2019]

8. Turkey pubmed.ncbi.nlm.nih.gov

Neuroprotective Effects of Pregabalin Against Spinal Cord Ischemia-Reperfusion Injury in Rats. [2018]