Metformin to Attenuate Progressive Respiratory Decline in Idiopathic Pulmonary Fibrosis

Официальное название

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

Обзор

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.

Подробное описание

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.

Вмешательства

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

Первичные конечные точки

• Time to death, non-elective hospitalization, or lung transplantation [Срок оценки: Baseline (visit 1) to up to 24 months]

Вторичные конечные точки (12)

• Time to all-cause mortality [Срок оценки: Baseline (visit 1) to up to 24 months]
• Time to first non-elective hospitalization [Срок оценки: Baseline (visit 1) to up to 24 months]
• Time to lung transplantation [Срок оценки: Baseline (visit 1) to up to 24 months]
• Time to respiratory hospitalization [Срок оценки: Baseline (visit 1) to up to 24 months]
• Change in Forced Vital Capacity (FVC) [Срок оценки: Baseline (visit 1) to 12 months]
• Change in Forced Vital Capacity (FVC) % Predicted [Срок оценки: Baseline (visit 1) to 12 months]
• Change in Diffusing Capacity of the Lungs for Carbon Monoxide (DLCO) corrected for hemoglobin. [Срок оценки: Baseline (visit 1) to 12 months.]
• Change in Six-Minute Walk Distance (6MWD) [Срок оценки: Baseline (visit 1) to 12 months]
• Change in patient reported outcomes scores for the Living with Pulmonary Fibrosis (L-PF) Impacts Questionnaire [Срок оценки: Baseline (visit 1) to 12 months]
• Change in patient reported outcomes scores for the Living with Pulmonary Fibrosis (L-PF) Impacts Questionnaire [Срок оценки: Baseline (visit 1) to 24 months]
• Change in patient reported outcomes scores for the Living with Pulmonary Fibrosis (L-PF) Symptoms Questionnaire [Срок оценки: Baseline (visit 1) to 12 months]
• Change in patient reported outcomes scores for the Living with Pulmonary Fibrosis (L-PF) Symptoms Questionnaire [Срок оценки: Baseline (visit 1) to 24 months]

Критерии участия

Критерии включения

• 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

Критерии исключения

• 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
• 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
• 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

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Четверное слепое

Основная цель

Лечение

Центры проведения

США · 1 центр

• University of Massachusetts Chan Medical School — Worcester

Идентификаторы

NCT: NCT07520110 · STUDY00002828 · PR241441

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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