Metformin to Attenuate Progressive Respiratory Decline in Idiopathic Pulmonary Fibrosis (MAVRIC)

April 8, 2026 updated by: Fernando J Martinez, University of Massachusetts, Worcester

Metformin to Attenuate Progressive Respiratory Decline in Idiopathic Pulmonary Fibrosis (MAVRIC)

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Not yet recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

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.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Estimated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
800

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Proteomic Signature Present - Metformin
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
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.
Placebo Comparator: Proteomic Signature Present - Placebo
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
Matching placebo over 12 to 24 months depending on time of enrollment into the trial.
No Intervention: Proteomic Signature Absent
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.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Time to death, non-elective hospitalization, or lung transplantation
Time Frame: Baseline (visit 1) to up to 24 months
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 Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Time to all-cause mortality
Time Frame: Baseline (visit 1) to up to 24 months
The time from randomization to death from any cause.
Baseline (visit 1) to up to 24 months
Time to first non-elective hospitalization
Time Frame: Baseline (visit 1) to up to 24 months
The time from randomization to the first unplanned inpatient hospital admission
Baseline (visit 1) to up to 24 months
Time to lung transplantation
Time Frame: Baseline (visit 1) to up to 24 months
The time from randomization to the date of a participant's lung transplant
Baseline (visit 1) to up to 24 months
Time to respiratory hospitalization
Time Frame: Baseline (visit 1) to up to 24 months
The time from randomization to the first non-elective respiratory hospitalization. Non-elective respiratory hospitalizations specifically refer to unplanned admissions where the primary cause is a pulmonary condition, as determined by a blinded adjudication committee.
Baseline (visit 1) to up to 24 months
Change in Forced Vital Capacity (FVC)
Time Frame: Baseline (visit 1) to 12 months
The longitudinal change in forced vital capacity (measured in liters) based on spirometry from baseline (visit 1) to 12 months.
Baseline (visit 1) to 12 months
Change in Forced Vital Capacity (FVC) % Predicted
Time Frame: Baseline (visit 1) to 12 months
The longitudinal change in FVC% predicted based on spirometry from baseline (visit 1) to 12 months.
Baseline (visit 1) to 12 months
Change in Diffusing Capacity of the Lungs for Carbon Monoxide (DLCO) corrected for hemoglobin.
Time Frame: Baseline (visit 1) to 12 months.
Units - ml/(min*mmHg)
Baseline (visit 1) to 12 months.
Change in Six-Minute Walk Distance (6MWD)
Time Frame: Baseline (visit 1) to 12 months
The longitudinal change in the maximum distance (in meters) a participant can walk on a flat surface in six minutes.
Baseline (visit 1) to 12 months
Change in patient reported outcomes scores for the Living with Pulmonary Fibrosis (L-PF) Impacts Questionnaire
Time Frame: Baseline (visit 1) to 12 months
The L-PF Impacts module contains 21 items (5-point Likert scale) that assesses the impact of disease on patients with pulmonary fibrosis. The range of the total score is 0-100, with higher scores indicating greater symptom severity.
Baseline (visit 1) to 12 months
Change in patient reported outcomes scores for the Living with Pulmonary Fibrosis (L-PF) Impacts Questionnaire
Time Frame: Baseline (visit 1) to 24 months
The L-PF Impacts module contains 21 items (5-point Likert scale) that assesses the impact of disease on patients with pulmonary fibrosis. The range of the total score is 0-100, with higher scores indicating greater symptom severity.
Baseline (visit 1) to 24 months
Change in patient reported outcomes scores for the Living with Pulmonary Fibrosis (L-PF) Symptoms Questionnaire
Time Frame: Baseline (visit 1) to 12 months
The L-PF Symptoms modules contains contains 23 items (5-point Likert scale) that assesses shortness of breath, cough, and fatigue within the last 24 hours. The range of the total score is 0-100, with higher scores indicating greater symptom severity.
Baseline (visit 1) to 12 months
Change in patient reported outcomes scores for the Living with Pulmonary Fibrosis (L-PF) Symptoms Questionnaire
Time Frame: Baseline (visit 1) to 24 months
The L-PF Symptoms modules contains contains 23 items (5-point Likert scale) that assesses shortness of breath, cough, and fatigue within the last 24 hours. The range of the total score is 0-100, with higher scores indicating greater symptom severity.
Baseline (visit 1) to 24 months
Change in patient reported outcomes scores for the R-Scale-PF
Time Frame: Baseline (visit 1) to 12 months
The R-Scale-PF is a 5-item numerical rating scale (NRS) to allow for rapid assessment of symptoms and health related quality of life (HRQoL). Scores range from 0 to 50, with lower scores indicating a better HRQoL.
Baseline (visit 1) to 12 months
Change in patient reported outcomes scores for the R-Scale-PF
Time Frame: Baseline (visit 1) to 24 months
The R-Scale-PF is a 5-item numerical rating scale (NRS) to allow for rapid assessment of symptoms and health related quality of life (HRQoL). Scores range from 0 to 50, with lower scores indicating a better HRQoL.
Baseline (visit 1) to 24 months
Change in Fatigue Severity Scale Score
Time Frame: From baseline (visit 1) to 12 months
The Fatigue Severity Scale (FSS) is a nine-item questionnaire used to assess the impact of fatigue on an individual's daily life. The FSS is a self-report measure about their level of fatigue on a scale of 1 to 7, with 7 indicating a higher level of fatigue.
From baseline (visit 1) to 12 months
Change in Fatigue Severity Scale Score
Time Frame: Baseline (visit 1) to 24 months
The Fatigue Severity Scale (FSS) is a nine-item questionnaire used to assess the impact of fatigue on an individual's daily life. The FSS is a self-report measure about their level of fatigue on a scale of 1 to 7, with 7 indicating a higher level of fatigue.
Baseline (visit 1) to 24 months
Incidence of Major Adverse Cardiac Events (MACE)
Time Frame: Baseline (visit 1) through final follow-up visit
The incidence of major adverse cardiac events (MACE), recorded from baseline (visit 1) through the final follow-up visit. MACE will be determined by the site investigator and defined as a composite of acute myocardial infarction, stroke, or death due to a cardiovascular cause.
Baseline (visit 1) through final follow-up visit
Rate of non-elective hospitalization
Time Frame: Baseline (visit 1) to 12 months
The rate of all non-elective hospitalizations from baseline (visit 1) to 12 months (number of hospitalizations per year).
Baseline (visit 1) to 12 months
Rate of non-elective hospitalization from baseline to 24 months
Time Frame: Baseline (visit 1) to 24 months
The rate of all non-elective hospitalizations from baseline (visit 1) to 24 months (number of hospitalizations per year).
Baseline (visit 1) to 24 months
Rate of Respiratory Hospitalizations
Time Frame: Baseline (visit 1) to 12 months

The rate of all non-elective respiratory hospitalizations from baseline (visit 1) to 12 months (number of hospitalizations per year).

Non-elective respiratory hospitalizations will be defined as any unplanned inpatient hospitalizations for which the primary cause was a pulmonary condition, in the opinion of the blinded adjudicators and based on all available clinical data.
Baseline (visit 1) to 12 months
Rate of Respiratory Hospitalizations
Time Frame: Baseline (visit 1) to 24 months

The rate of all non-elective respiratory hospitalizations from baseline (visit 1) to 24 months (number of hospitalizations per year)

Non-elective respiratory hospitalizations will be defined as any unplanned inpatient hospitalizations for which the primary cause was a pulmonary condition, in the opinion of the blinded adjudicators and based on all available clinical data.
Baseline (visit 1) to 24 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
University of Massachusetts, Worcester

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
United States Department of Defense

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Sydney Montesi, MD, Massachusetts General Hospital
  • Principal Investigator: Fernando Martinez, MD, MS, UMass Chan Medical School
  • Principal Investigator: Bhavika Kaul, MD, MAS, Michael E. DeBakey Veterans Affairs Medical Center (MEDVAMC)

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
August 1, 2026

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
March 15, 2029

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
March 15, 2029

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
April 2, 2026

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
April 2, 2026

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
April 9, 2026

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
April 14, 2026

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
April 8, 2026

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
April 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • STUDY00002828
  • PR241441 (Other Grant/Funding Number: Department of Defense)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

This study will be conducted in accordance with the publication and data sharing policies and regulations from the Department of Defense Research and Development General Terms and Conditions.

De-identified samples and data may be shared with other researchers, institutions, and collaborating for-profit companies within and outside of the United States upon approval of the Ancillary Committee. Data from this study may be requested after the completion of the primary endpoint by contacting the Collaborating Studies Coordinating Center (CSCC) at The University of North Carolina at Chapel Hill.

IPD Sharing Time Frame

One year from the study completion date.

IPD Sharing 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.

IPD Sharing Supporting Information Type

  • STUDY_PROTOCOL
  • SAP

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

Yes

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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