Metformin to Attenuate Progressive Respiratory Decline in Idiopathic Pulmonary Fibrosis

NCT07520110 | Not Yet Recruiting Phase 3 DMC FDA Drug

• 2 other identifiers: STUDY00002828PR241441
• Study Type: interventional
• Target: 800
• Locations: 1 country
• Sites: 1

Brief Summary

This is a randomized, placebo-controlled trial of metformin in 400 participants with idiopathic pulmonary fibrosis (IPF) who are at high risk of adverse clinical outcomes based on a proteomic classifier. The primary objective is to assess the safety and efficacy of metformin compared to placebo in participants with IPF who are at high-risk for adverse clinical events. Approximately 800 participants with IPF will be screened. 400 participants who are at high risk for adverse clinical events (proteomic signature present) will be randomized into receiving metformin (n\~200) or matching placebo (n\~200). Participants that meet the eligibility criteria but do not have the proteomic signature (proteomic signature absent) will be contacted by phone at 12 and 24 months to review medical history.

Conditions

Idiopathic Pulmonary Fibrosis

Keywords

Idiopathic Pulmonary Fibrosis; IPF; metformin

Outcome Measures

Primary Outcomes (1)

• Time to death, non-elective hospitalization, or lung transplantation

  Clinical composite measure defined as the time from randomization to the first occurrence of any of its three components: all-cause mortality, first unplanned (non-elective) hospitalization, or lung transplantation.

  Baseline (visit 1) to up to 24 months

Secondary Outcomes (21)

• Time to all-cause mortality

  Baseline (visit 1) to up to 24 months

• Time to first non-elective hospitalization

  Baseline (visit 1) to up to 24 months

• Time to lung transplantation

  Baseline (visit 1) to up to 24 months

• Time to respiratory hospitalization

  Baseline (visit 1) to up to 24 months

• Change in Forced Vital Capacity (FVC)

  Baseline (visit 1) to 12 months

Study Arms (3)

Proteomic Signature Present - Metformin

EXPERIMENTAL

200 participants who have a screening blood test result that is proteomic signature present will be randomized to oral metformin at a total target daily dose of 1500mg per day for 12 to 24 months depending on time of enrollment into the trial.

Drug: Metformin

Proteomic Signature Present - Placebo

PLACEBO COMPARATOR

200 participants who have a screening blood test result that is proteomic signature present will be randomized to matching placebo 12 to 24 months depending on time of enrollment into the trial.

Drug: Matching Placebo

Proteomic Signature Absent

NO INTERVENTION

Participants that meet the eligibility criteria but do have a screening blood test result that is proteomic signature absent (about 400 participants) will be asked to attend 2 follow-up remote visits at 12 and 24 months. This arm will be observational only.

Interventions

Metformin DRUG

Metformin or matching placebo over 12 to 24 months depending on time of enrollment into the trial. The dose will be increased by 500 mg every 14 days to a total target daily dose of 1500 mg.

Proteomic Signature Present - Metformin

Matching Placebo DRUG

Matching placebo over 12 to 24 months depending on time of enrollment into the trial.

Proteomic Signature Present - Placebo

Eligibility Criteria

• Age: 40 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• IPF diagnosis by enrolling investigator (following the 2022 updated guidelines on diagnosis and management of IPF)
• Age 40 years or older
• HbA1c \< 9% at screening
• 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).
• If on FDA-approved treatment(s) for IPF, on a stable dose for at least 8 weeks prior to randomization
• Ability to provide informed consent

You may not qualify if:

• Taking metformin within 3 months of randomization
• Allergy or intolerance to metformin
• Use of insulin or insulin secretagogue(s) at randomization
• Pregnancy, planning to become pregnant, or lactating
• 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
• History of biochemically-confirmed acidosis (lactate \> 5.0 mmol/L)
• Estimated glomerular filtration rate less than 45 mL/min/1.73 m2 at screening
• Receipt of an investigational study agent as part of a therapeutic trial within 30 days of the Screening Visit (Visit 0)
• Continuous supplemental oxygen use at rest greater than 2 L/min
• Unable to swallow pills
• 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.
• 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
• Listed for transplant at the time of randomization

Sponsors & Collaborators

• University of Massachusetts, Worcester: lead
• United States Department of Defense: collaborator

Study Sites (1)

University of Massachusetts Chan Medical School

Worcester, Massachusetts, 01655, United States

Location

MeSH Terms

Conditions

Idiopathic Pulmonary Fibrosis

Interventions

Metformin

Condition Hierarchy (Ancestors)

Pulmonary Fibrosis; Lung Diseases, Interstitial; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Biguanides; Guanidines; Amidines; Organic Chemicals

Study Officials

• Fernando Martinez, MD, MS

  UMass Chan Medical School

  PRINCIPAL INVESTIGATOR

• Sydney Montesi, MD

  Massachusetts General Hospital

  PRINCIPAL INVESTIGATOR

• Bhavika Kaul, MD, MAS

  Michael E. DeBakey Veterans Affairs Medical Center (MEDVAMC)

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Model Details: Participants with a proteomic signature present are randomized into two separate, concurrent groups-one receiving the active drug (metformin) and the other a matching placebo-and remain in their assigned arm for the entire 12-to-24-month duration.

Study Record Dates

• First Submitted: April 2, 2026
• First Posted: April 9, 2026
• Study Start (Estimated): August 1, 2026
• Primary Completion (Estimated): March 15, 2029
• Study Completion (Estimated): March 15, 2029
• Last Updated: April 14, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: One year from the study completion date.
• Access Criteria: Data will be made available by the University of North Carolina at Chapel Hill upon approval of the request by the MAVRIC-IPF Ancillary Committee.

Locations

US (1)