Use of Metformin in Prevention and Treatment of Cardiac Fibrosis in PAI-1 Deficient Population

R2O210069

This study will evaluate the efficacy and safety of metformin, in patients 18-65 years of age with homozygous plasminogen activator inhibitor-1 (PAI-1) deficiency, with or without cardiac fibrosis, for a period of 60 months. The starting dose of metformin will be 500 mg up to a maximum dose of 2000 mg for a period of 5 years with the aim to assess the safety and efficacy of metformin on prevention/stabilization or regression of cardiac fibrosis in a Treated population vs. a Comparison population.

2022-10-10

2027-10-01

2027-10-01

Active (not recruiting)

Early phase I

15

Inclusion Criteria: * Confirmed homozygosity for mutation in SERPINE-1 for PAI-1 deficiency * Male or female * Aged 18-65 years * Willing and able to choose between being in a metformin Treatment group (daily metformin) or an Observation group (no study drug) at study entry * Capable of understanding and willing to comply with the conditions of the study (in the opinion of the study investigator(s)) * Have read, understood and be able to provide written informed consent Exclusion Criteria: * Not homozygous for SERPINE-1 mutation for PAI-1 deficiency, based on genetic testing * Ages \<18 or \>65 years * Renal dysfunction (Cockcroft Gault CrCl \< 30) * History of hypersensitivity of metformin or any component in the extended release formulation * Unwillingness to avoid alcohol * Currently prescribed cimetidine, dolutegravir, patiromer, ranolazine, or tafenoquine and no alternate therapy is possible * History of illicit drug or alcohol abuse within 48 weeks prior to screening, in the study investigators' judgment * Concomitant disease, condition, significant abnormality on screening evaluations or laboratory tests, or treatment that could interfere with the conduct of the study, or that would, in the opinion of the study investigator(s), pose an additional unacceptable risk in administering study drug to the patient * Receipt of any other investigational medicinal product currently being administered (or planned to be administered) * Inability to comply with the study protocol (in the opinion of the study investigator(s)) * Inability to understand and provide written informed consent

{'studyType': 'INTERVENTIONAL', 'phases': ['PHASE4'], 'designInfo': {'allocation': 'NON_RANDOMIZED', 'interventionModel': 'PARALLEL', 'interventionModelDescription': 'The study will have one metformin Treatment group (daily metformin administered) and one Observation group (no study drug administered)', 'primaryPurpose': 'TREATMENT', 'maskingInfo': {'masking': 'NONE'}}, 'enrollmentInfo': {'count': 15, 'type': 'ESTIMATED'}}

2023-09-29