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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines whether Glyburide, a medication commonly used for diabetes, can protect nerves in individuals with recent spinal cord injuries in the neck or upper back. The primary goal is to determine its safety and effectiveness for these injuries. Participants should have non-penetrating spinal cord injuries and no severe injuries from the accident. This study excludes individuals with a history of severe kidney or liver problems, specific heart issues, or allergies to the medication. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this potentially groundbreaking treatment.

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.

Is there any evidence suggesting that Glyburide is likely to be safe for humans?

Research has shown that Glyburide has been used successfully in animal studies to protect the spinal cord after injury. In these studies, Glyburide reduced bleeding in the spinal cord when administered soon after the injury, suggesting it might help limit damage.

Glyburide is also a well-known medication for diabetes, providing extensive information about its safety from its use in that condition. However, its use for spinal cord injuries is still under investigation, so new side effects may emerge.

As this trial is in an early stage, the main goal is to assess Glyburide's safety for people with spinal cord injuries. Researchers are closely monitoring any side effects that may occur when using it for this new purpose. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about using Glyburide for spinal cord injury because it offers a different approach compared to current treatments. Most existing therapies focus on managing symptoms or providing physical rehabilitation. However, Glyburide works by potentially reducing the secondary damage caused by inflammation and swelling after the initial injury. This could help preserve more nerve cells and improve recovery outcomes, making it a promising option beyond standard care methods.

What evidence suggests that Glyburide might be an effective treatment for spinal cord injury?

Research has shown that Glyburide, which participants in this trial will receive, may protect the nervous system in individuals with spinal cord injuries. In animal studies, Glyburide led to better outcomes, such as smaller injury areas and improved limb movement. It targets specific channels in the body that become more active after an injury, helping to prevent further damage. Glyburide has also successfully treated strokes caused by blocked blood flow, suggesting potential benefits for spinal cord injuries. These findings offer hope for its effectiveness in people with sudden spinal cord injuries. ^{1 2 4 6 7}

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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 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]

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]

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 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]

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]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6797422/

SCING—Spinal Cord Injury Neuroprotection with Glyburide Lesion volumes and hindlimb locomotor functional outcome measures, measured up to 6 weeks, are significantly improved in animals treated with ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT02524379

Spinal Cord Injury Neuroprotection With Glyburide 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).

3. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/31601596/

SCING-Spinal Cord Injury Neuroprotection with Glyburide Glyburide has been shown as an effective neuroprotective agent in preclinical tSCI models and in the treatment of ischaemic stroke with the additional risk of ...

4. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0014488610004176

Independent evaluation of the effects of glibenclamide on ... In experimental spinal cord injury, glibenclamide diminishes the development of hemorrhagic necrosis, leading to improved neurological outcome (Simard et al ...

5. bmjopen.bmj.com bmjopen.bmj.com/content/9/10/e031329.reviewer-comments

SCING—Spinal Cord Injury Neuroprotection with Glyburide The authors stated that the results of animal experiments showed the up-regulation of Sur1-Trpm4 channel, a target of glyburide, from 6h to 24h ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT05426681

Study Details | NCT05426681 | Spinal Cord Injury ... 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 ...

7. sciencedirect.com sciencedirect.com/science/article/pii/S135964462500100X

Navigating the complexities of spinal cord injury A prospective multicenter study has demonstrated that earlier surgical intervention (within 24 h post-injury) results in significantly better functional ...