The research plan is divided into three work packages (WP):~WP0, Bone Marrow Adipose Tissue (BMAT) in CCUS and LR-MDS Patients: The primary objective of WP0 is to determine if patients with CCUS or LR-MDS have increased BMAT compared to age-matched healthy controls. To investigate this, we will include 12 elderly (≥60 years) healthy controls who will have their BMAT measured by magnetic resonance spectroscopy (MRS). These will be compared to the BMAT measurements from baseline of patients described in WP1.~WP1, The efficacy of metformin in CCUS and LR-MDS: In WP1, 24 patients with either CCUS or MDS will receive metformin 2000 mg/daily for 12 months with a slow-up-titration of the dose 14 days prior to full-dose treatment. Outcomes of WP1 are listed in the outcome section on this site.~WP2, The efficacy of metformin compared to placebo and vitamin C: The primary objective of WP2 is to compare the effect of metformin in CCUS and LR-MDS to the effect of placebo or vitamin C treatment. To investigate this, we will include data and samples from 48 historical controls from our EVI-2 study (NCT03999723. Half of the controls received placebo for 12 months and the other half received vitamin C for 12 months.
This is a phase 2 single-arm pilot study of the efficacy and safety of metformin in patients with clonal cytopenia of undetermined significance (CCUS) or lower-risk myelodysplastic syndrome (MDS).