Metformin to Attenuate Progressive Respiratory Decline in Idiopathic Pulmonary Fibrosis

What this trial studies

This is a multi-center, randomized, double-blind, placebo-controlled trial, of metformin or placebo in 400 participants with idiopathic pulmonary fibrosis (IPF) who are at high risk of adverse clinical outcomes based on a proteomic classifier. Eligible participants will be placed into 2 groups depending on the results of their proteomic signature blood test done at the Screening Visit (Visit 0). * Eligible participants who have the proteomic signature present will be randomized in a 1:1 fashion to either metformin at Visit 1 (Enrollment/Baseline) and attend follow-up visits at Months 1, 3, 6, 12, 18, 24, and a follow-up phone call at 25 months. Randomization will be stratified by background FDA-approved IPF therapy (yes/no) and DM status (yes/no). * Eligible participants who are proteomic signature absent will be asked to complete 2 follow-up remote visits at Months 12 and 24. The metformin starting dose will be 500 mg daily of extended-release formulation or matching placebo. The dose will be increased by 500 mg every 14 days to a total target daily dose of 1500 mg. Participants will be followed for a minimum of 12 months and a maximum of approximately 25 months, depending on the date of randomization.

Who can join: the full rules

Inclusion Criteria:

1. IPF diagnosis by enrolling investigator (following the 2022 updated guidelines on diagnosis and management of IPF)
2. Age 40 years or older
3. HbA1c \< 9% at screening
4. High risk by proteomic signature (proteomic signature present) for participants randomized only (for participants randomized only; participants that are proteomic signature absent will undergo remote study assessments at 12 and 24 months only).
5. If on FDA-approved treatment(s) for IPF, on a stable dose for at least 8 weeks prior to randomization
6. Ability to provide informed consent

Exclusion Criteria:

1. Taking metformin within 3 months of randomization
2. Allergy or intolerance to metformin
3. Use of insulin or insulin secretagogue(s) at randomization
4. Pregnancy, planning to become pregnant, or lactating
5. Women of childbearing potential not willing to remain abstinent (refrain from heterosexual intercourse) or use two adequate methods of contraception, including at least one method with a failure rate of \<1% per year during study participation
6. History of biochemically-confirmed acidosis (lactate \> 5.0 mmol/L)
7. Estimated glomerular filtration rate less than 45 mL/min/1.73 m2 at screening
8. Moderate-to-severe liver disease, decompensated heart failure, or any other condition that may make the participant unsuitable for inclusion as assessed by the study investigator at each site
9. Receipt of an investigational study agent as part of a therapeutic trial within 30 days of the Screening Visit (Visit 0)
10. Continuous supplemental oxygen use at rest greater than 2 L/min
11. Unable to swallow pills
12. Taking a medication that has a major interaction with metformin, including acetazolamide (Diamox), cimetidine (Tagamet), dolutegravir, gatifloxacin, levoketoconazole, ranolazine, or carbonic anhydrase inhibitors. Occasional use of carbonic anhydrase inhibitors for travel is permitted.
13. Current alcohol intake ≥ 15 drinks per week in men, ≥ 8 drinks per week in women or ≥ 5 drinks per occasion in men, ≥ 4 drinks per occasion in women
14. Listed for transplant at the time of randomization

Where it's running

• University of Arizona
  Tucson, Arizona, United States
• University of Colorado Anschutz
  Aurora, Colorado, United States
• Georgetown University Hospital
  Washington D.C., District of Columbia, United States
• Northwestern University
  Chicago, Illinois, United States
• University of Chicago
  Chicago, Illinois, United States
• Massachusetts General Hospital
  Boston, Massachusetts, United States

Study contacts

• Principal investigator: Fernando Martinez, MD, MS — UMass Chan Medical School

How to take part

1. Review the eligibility criteria above with your treating physician.
2. Check the official listing on ClinicalTrials.gov for the latest contact details and recruitment status.
3. Contact the study coordinator or principal investigator to ask for pre-screening. Pre-screening is free and never obligates you to enroll.