Metformin for Burns

(MET-ELD Trial)

Recruiting at 1 trial location

Overseen By Marc G Jeschke, MD PhD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Sunnybrook Health Sciences Centre

Must not be taking: Insulin

Disqualifiers: Renal failure, Severe liver disease, others

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 6 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 1-4 months

250 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial is testing if metformin, a diabetes medication, can help elderly burn patients recover better by controlling blood sugar and reducing inflammation and metabolic stress. Metformin is widely used for diabetes and has shown potential benefits beyond controlling blood sugar, including reducing inflammation.

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 have insulin-dependent type II diabetes or a clinical contraindication to metformin, you may not be eligible to participate.

What data supports the effectiveness of the drug metformin for treating burns?

Research shows that metformin can help control high blood sugar and reduce muscle breakdown in patients with severe burns, which can improve healing and immune function. It also helps manage the body's energy use and inflammation, potentially leading to better recovery outcomes. ^{1 2 3 4 5}

Is metformin safe for use in burn patients?

Metformin is generally safe for use in humans, but there is a risk of lactic acidosis (a buildup of lactic acid in the body) in burn patients, as seen in one case. It is important to monitor for this condition when using metformin in such patients. ^{3 4 5 6 7}

How does the drug metformin differ from other treatments for burns?

Metformin is unique because it is primarily a diabetes medication that also has anti-inflammatory and potential anticancer properties, which might help in treating burns by reducing inflammation and promoting healing, unlike traditional burn treatments that focus on wound care and infection prevention. ^{8 9 10 11 12}

Research Team

Marc G Jeschke, MD PhD

Principal Investigator

Hamilton Health Sciences Corporation

Eligibility Criteria

This trial is for elderly patients aged 60-99 with significant burn injuries, who are likely to need surgery and can consent to treatment. They must have a burn covering at least 5% of their body but cannot join if they're critically ill on admission, have severe pre-existing conditions like kidney or liver failure, allergies to metformin, or a history of lactic acidosis with metformin.

Inclusion Criteria

I was admitted to a burn center within 5 days after getting burned.

Provide written informed consent

I have burns covering 5% or more of my body.

Exclusion Criteria

I cannot take metformin due to health reasons.

I have had lactic acidosis from metformin before.

I have a brain injury from lack of oxygen and am not expected to fully recover.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive metformin or placebo and are monitored for episodes of sepsis, organ function, and metabolic response

1-4 months

Daily assessments during hospital stay

Follow-up

Participants are monitored for mortality and organ function post-discharge

Up to 1 year post burn

Treatment Details

Interventions

• Metformin

Trial Overview The study tests whether the drug Metformin reduces complications and death rates in elderly patients with burns compared to a placebo. The hypothesis is that Metformin will help manage the intense inflammatory and metabolic reactions following a burn injury.

Participant Groups

Group I: Metformin Experimental Treatment 1 Intervention

Group II: Control Placebo Group 1 Intervention

Metformin is already approved in European Union, United States, Canada, Japan, China, Switzerland for the following indications:

Approved in European Union as Glucophage for:

• Type 2 diabetes

Approved in United States as Glucophage for:

• Type 2 diabetes

Approved in Canada as Glucophage for:

• Type 2 diabetes

Approved in Japan as Glucophage for:

• Type 2 diabetes

Approved in China as Glucophage for:

• Type 2 diabetes

Approved in Switzerland as Glucophage for:

• Type 2 diabetes

Who Is Running the Clinical Trial?

Sunnybrook Health Sciences Centre

Lead Sponsor

Trials

693

Recruited

1,569,000+

Hamilton Health Sciences Corporation

Lead Sponsor

Trials

380

Recruited

345,000+

Findings from Research

Dapagliflozin, a selective SGLT2 inhibitor, has been shown to improve glycaemic control in adults with type 1 diabetes (T1D) and a BMI of ≥27 kg/m2, allowing for reduced insulin doses and weight loss over 24 weeks, with effects maintained up to 52 weeks.

The drug has a favorable safety profile, with a lower incidence of diabetic ketoacidosis in patients with higher BMI compared to the overall population, making it a promising adjunct treatment for those not achieving adequate control with insulin alone.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dapagliflozin: A Review in Type 1 Diabetes. Paik, J., Blair, HA.[2021]

In a phase II clinical trial involving 81 patients with recurrent or refractory glioblastoma, the combination of metformin and low-dose temozolomide was well tolerated but did not show a significant clinical benefit in terms of progression-free survival or overall survival compared to the control group receiving placebo and temozolomide.

The median overall survival was 17.22 months for the metformin group versus 7.69 months for the control group, but this difference was not statistically significant, indicating that metformin may not improve outcomes in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of metformin plus low-dose temozolomide in patients with recurrent or refractory glioblastoma: a randomized, prospective, multicenter, double-blind, controlled, phase 2 trial (KNOG-1501 study). Yoon, WS., Chang, JH., Kim, JH., et al.[2023]

References

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

Metformin adapts its cellular effects to bioenergetic status in a model of metabolic dysfunction. [2019]

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

Influence of metformin on glucose intolerance and muscle catabolism following severe burn injury. [2019]

3. England pubmed.ncbi.nlm.nih.gov

Metformin-associated lactic acidosis in a burn patient. [2019]

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

Metformin blunts stress-induced hyperglycemia after thermal injury. [2013]

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

Comparison of peripheral metabolic effects of insulin and metformin following severe burn injury. [2019]

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

Glucose Control in Severely Burned Patients Using Metformin: An Interim Safety and Efficacy Analysis of a Phase II Randomized Controlled Trial. [2021]

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

Dapagliflozin: A Review in Type 1 Diabetes. [2021]

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

Efficacy and safety of metformin plus low-dose temozolomide in patients with recurrent or refractory glioblastoma: a randomized, prospective, multicenter, double-blind, controlled, phase 2 trial (KNOG-1501 study). [2023]

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

Metformin inhibits the inflammatory response associated with cellular transformation and cancer stem cell growth. [2021]

10. Ukraine pubmed.ncbi.nlm.nih.gov

Cytotoxic activity of metformin in vitro does not correlate with its antitumor action in vivo. [2018]

11. England pubmed.ncbi.nlm.nih.gov

Prognostic and predictive value of metformin in the European Organisation for Research and Treatment of Cancer 1325/KEYNOTE-054 phase III trial of pembrolizumab versus placebo in resected high-risk stage III melanoma. [2023]

12. Greece pubmed.ncbi.nlm.nih.gov

Metformin Prevents Peritoneal Dissemination via Immune-suppressive Cells in the Tumor Microenvironment. [2019]