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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether metformin, a common diabetes medication, can treat acute kidney injury (AKI) caused by sepsis, a serious infection. Sepsis often leads to AKI, which can be life-threatening, and currently, no treatments can reverse it. Participants will receive either a high dose or low dose of metformin, or a placebo, to determine if the drug is safe and feasible for this use. Eligible participants are those in the ICU due to sepsis who have not recently taken metformin. As a Phase 2 trial, this research measures how well metformin works in an initial, smaller group, offering a chance to contribute to potential new treatments for AKI.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research suggests that metformin, a common diabetes medication, might help with kidney problems caused by sepsis. Studies have shown that metformin can activate a protein that protects the kidneys from damage, which could benefit people with sepsis-related acute kidney injury (AKI).

Metformin is generally well-tolerated and has been used safely for many years in people with diabetes. However, the doses in this study specifically address sepsis-related issues. Previous patients have shown that both low and high doses of metformin are usually safe, but monitoring for side effects is important. Common side effects might include stomach upset or diarrhea, but these are usually mild.

This research is in an early phase, focusing on safety and practicality. So far, metformin looks promising, but more studies are needed to confirm its safety for treating AKI in sepsis patients. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about using metformin for sepsis-induced acute kidney injury (AKI) because it offers a fresh approach compared to traditional treatments like fluid management and renal replacement therapy. Metformin, commonly known for managing diabetes, shows potential in reducing inflammation and improving cellular energy balance in kidney cells, which could help prevent or mitigate AKI in sepsis patients. The trial explores both high and low doses of metformin to determine its effectiveness and safety, providing a potentially faster and more targeted treatment option for this critical condition.

What evidence suggests that this trial's treatments could be effective for sepsis-induced AKI?

This trial will compare the effects of different doses of metformin on sepsis-induced acute kidney injury (AKI). Research has shown that metformin might benefit people with sepsis-related AKI by reducing inflammation and protecting cells from damage, thereby lessening harm to organs. Studies have found that metformin activates a protein called AMPK, which can protect the kidneys and improve survival chances. Patients who took metformin before developing sepsis had better outcomes, such as lower death rates. While earlier studies mainly focused on safety, these findings suggest that metformin could be a useful treatment for AKI in sepsis patients. Participants in this trial will receive either a high dose (1,000 mg), a low dose (500 mg) of metformin, or a placebo to evaluate its effectiveness in this context. ^{1 2 3 4 6}

Who Is on the Research Team?

Hernando Gomez, MD

Principal Investigator

University of Pittsburgh

Are You a Good Fit for This Trial?

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

I am older than 18 years.

Exclusion Criteria

I have taken Metformin in the last 30 days.

Advanced directive to withhold life-sustaining treatment

History of allergy to metformin

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11086423/

Metformin for sepsis-associated AKI: a protocol for the ... Acute kidney injury (AKI) is a common complication of sepsis associated with increased risk of death. Preclinical data and observational human ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT05900284?tab=table

Safety and Feasibility of Metformin for Sepsis Induced AKI This proposal aims to conduct a randomized, placebo-controlled, feasibility study to establish the safety and feasibility of the use of oral metformin to ...

3. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/38688665/

Metformin for sepsis-associated AKI: a protocol for ... - PubMed LiMiT AKI aims to evaluate the safety and feasibility of enteral metformin in patients with sepsis at risk of developing SA-AKI.

4. ctv.veeva.com ctv.veeva.com/study/safety-and-feasibility-of-metformin-for-sepsis-induced-aki

Safety and Feasibility of Metformin for Sepsis Induced AKI Investigators have shown that pharmacologic activation of AMPK protects from AKI and improves survival, while inhibition increases kidney injury ...

5. withpower.com withpower.com/trial/phase-2-toxemia-5-2023-aad64

Metformin for Sepsis-Induced AKI · Info for Participants Metformin is unique in treating sepsis-induced acute kidney injury (AKI) because it has anti-inflammatory and antioxidant properties that may help reduce organ ...

6. researchgate.net researchgate.net/publication/380226752_Metformin_for_sepsis-associated_AKI_a_protocol_for_the_Randomized_Clinical_Trial_of_the_Safety_and_FeasibiLity_of_Metformin_as_a_Treatment_for_sepsis-associated_AKI_LiMiT_AKI

(PDF) Metformin for sepsis-associated AKI: a protocol for ... Patients will be randomised 1:1:1 to low-dose metformin (500 mg two times per day), high-dose metformin (1000 mg two times per day) or placebo ...