Metformin for Sepsis-Induced AKI

Overseen By Howard R Stein, MS

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Hernando Gomez

Must not be taking: Metformin

Disqualifiers: Low eGFR, Pregnancy, Mechanical support, others

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

Compensation: Varies

Number of Visits: 32

Duration: 5 days

80 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial is testing if metformin, a diabetes drug, can help patients with severe infections who develop kidney problems. The drug works by activating a protein that protects the kidneys. Researchers want to see if it is safe and effective for these patients. Metformin has been studied for its effects on kidney function, with some studies suggesting potential harmful effects and others indicating possible protective benefits.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, if you have used metformin in the last 30 days, you cannot participate in the trial.

What data supports the effectiveness of the drug Metformin for treating sepsis-induced acute kidney injury (AKI)?

Research suggests that Metformin, a drug commonly used for diabetes, may help reduce inflammation and organ damage in sepsis, including liver injury, which could be beneficial for sepsis-induced AKI. Some studies indicate that patients who were already taking Metformin before developing sepsis had better outcomes, such as lower mortality rates. ^{1 2 3 4 5}

Is metformin safe for use in humans, particularly in the context of sepsis?

Studies have reported that metformin is generally safe at therapeutic doses in septic patients, with no evidence of lactic acidosis (a condition where lactic acid builds up in the bloodstream faster than it can be removed). ^{1 2 3 5 6}

How does the drug metformin differ from other treatments for sepsis-induced AKI?

Metformin is unique in treating sepsis-induced acute kidney injury (AKI) because it has anti-inflammatory and antioxidant properties that may help reduce organ damage and improve outcomes. Unlike other treatments, metformin works by activating AMPK (a protein that helps regulate energy balance) and reducing inflammation, which could be beneficial in managing sepsis-related complications. ^{2 3 5 6 7}

Research Team

Hernando Gomez, MD

Principal Investigator

University of Pittsburgh

Eligibility Criteria

This trial is for adults in the ICU with sepsis or septic shock who can take oral medication and meet specific criteria indicating early-stage kidney injury due to sepsis. It's not for those with type 1 diabetes, advanced kidney injury, pregnancy, severe metabolic acidosis, recent metformin use, or expected short survival.

Inclusion Criteria

Available enteral access

I am older than 18 years.

I was admitted to the ICU for a severe infection with worsening health.

Exclusion Criteria

I have taken Metformin in the last 30 days.

Advanced directive to withhold life-sustaining treatment

The treating clinician believes that participation in the trial would not be in the best interests of the patient

Timeline

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Treatment

Participants receive metformin or placebo for 5 days to assess safety and feasibility in treating sepsis-induced AKI

5 days

Daily visits for monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment, including assessment of AKI and adverse events

Up to 30 days or until hospital discharge

Regular monitoring until discharge or day 30

Pharmacokinetic Assessment

Assessment of metformin absorption and accumulation through blood samples

5 days

Blood samples on Day 2 and Day 5

Treatment Details

Interventions

• Metformin high dose
• Metformin low dose
• Placebo

Trial Overview The study tests low and high doses of metformin against a placebo to see if it's safe and feasible for treating acute kidney injury caused by sepsis. This initial step could lead to larger trials assessing its effectiveness in reversing such injuries.

Participant Groups

Group I: Metformin 500 mg Experimental Treatment 1 Intervention

One 500mg tablet will be administered twice a day for the first (5) days of study treatment.

Group II: Metformin 1,000 mg Experimental Treatment 1 Intervention

One 1,000mg tablet will be administered twice a day for the first (5) days of study treatment.

Group III: Placebo Placebo Group 1 Intervention

One inactive tablet will be administered twice a day for the first (5) days of study treatment.

Who Is Running the Clinical Trial?

Hernando Gomez

Lead Sponsor

Trials

2

Recruited

130+

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Collaborator

Trials

2,513

Recruited

4,366,000+

National Institutes of Health (NIH)

Collaborator

Trials

2,896

Recruited

8,053,000+

References

1. Japan pubmed.ncbi.nlm.nih.gov

Association between prior metformin therapy and sepsis in diabetes patients: a nationwide sample cohort study. [2020]

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

Metformin attenuated sepsis-associated liver injury and inflammatory response in aged mice. [2022]

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

New potential for an old kid on the block: Impact of premorbid metformin use on lactate kinetics, kidney injury and mortality in sepsis and septic shock, an observational study. [2023]

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

Association of Metformin Use During Hospitalization and Mortality in Critically Ill Adults With Type 2 Diabetes Mellitus and Sepsis. [2023]

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

The Association of Premorbid Metformin Exposure With Mortality and Organ Dysfunction in Sepsis: A Systematic Review and Meta-Analysis. [2022]

6. Iran pubmed.ncbi.nlm.nih.gov

A Review on The Protective Effects of Metformin in Sepsis-Induced Organ Failure. [2020]

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

Impact of Metformin Use on Lactate Kinetics in Patients with Severe Sepsis and Septic Shock. [2022]