Adjunctive Resveratrol or Omeprazole in Patients with Non-Transfusion-Dependent Thalassemia with Iron Overload: A Randomized, Double-Blind, Placebo-Controlled Trial

Increased gastrointestinal iron absorption contributes substantially to iron overload in non-transfusion-dependent thalassemia (NTDT) patients. Resveratrol (RVT) and omeprazole (OMP) may reduce intestinal iron absorption and potentially complement iron chelation therapy. This randomized, double-blind, placebo-controlled trial evaluated the efficacy and safety of adjunctive RVT or OMP in adults with NTDT receiving stable iron chelation therapy. The primary outcome was the change in serum ferritin; secondary outcomes influenced serum iron (SI), transferrin saturation (TS), erythroferrone (ERFE), hepcidin, fetal hemoglobin (HbF), and safety. Participants with serum ferritin ≥ 300 ng/mL were randomized (1:1:1) to receive RVT 250 mg, OMP 20 mg, or the placebo (PLA) twice daily for 6 months. Thirty participants were randomized (RVT, n = 10; OMP, n = 11; PLA, n = 9), with a baseline median serum ferritin value of 629 ng/mL, interquartile range (IQR) 484–975. Serum ferritin decreased numerically over 6 months in the RVT and OMP groups relative to PLA; however, no significant treatment × time interactions or adjusted between-group differences in changes from the baseline were observed. Although significant within-group changes were observed for selected iron-regulatory biomarkers, including hepcidin, ERFE, and TS, these were not accompanied by significant treatment × time interactions and did not demonstrate differential treatment effects. Both interventions were generally well tolerated, and no serious adverse events were reported. In this underpowered trial, neither adjunctive RVT nor OMP demonstrated statistically significant treatment-specific effects on serum ferritin or other iron-related outcomes when compared with the placebo. The observed numerical trends warrant evaluation in larger, adequately powered trials. Trial Registration: ISRCTN73258526.