Isoquercetin for thromboinflammation in sickle cell disease: a randomized double-blind placebo-controlled trial.

Autor:	Lizarralde-Iragorri MA; Sickle Thrombosis and Vascular Biology Lab, Sickle Cell Branch, National Heart Lung and Blood Institute, National Institutes of Health, Bethesda, MD., Parachalil Gopalan B; Sickle Thrombosis and Vascular Biology Lab, Sickle Cell Branch, National Heart Lung and Blood Institute, National Institutes of Health, Bethesda, MD., Merriweather B; Sickle Cell Branch, National Heart Lung and Blood Institute, National Institutes of Health, Bethesda, MD., Brooks J; Office of the Clinical Director, National Heart Lung and Blood Institute, National Institutes of Health, Bethesda, MD., Hill M; Office of the Clinical Director, National Heart Lung and Blood Institute, National Institutes of Health, Bethesda, MD., Lovins D; Office of the Clinical Director, National Heart Lung and Blood Institute, National Institutes of Health, Bethesda, MD., Pierre-Charles R; Office of the Clinical Director, National Heart Lung and Blood Institute, National Institutes of Health, Bethesda, MD., Cullinane A; Department of Laboratory Medicine, Clinical Center, National Institutes of Health, Bethesda, MD., Dulau-Florea A; Department of Laboratory Medicine, Clinical Center, National Institutes of Health, Bethesda, MD., Lee DY; Biochemistry Core Facility, National Heart Lung and Blood Institute, National Institutes of Health, Bethesda, MD., Villasmil R; Flow Cytometry Core Facility, National Eye Institute, National Institutes of Health, Bethesda, MD., Jeffries N; Office of Biostatistics Research, National Heart Lung and Blood Institute, National Institutes of Health, Bethesda, MD., Shet AS; Sickle Thrombosis and Vascular Biology Lab, Sickle Cell Branch, National Heart Lung and Blood Institute, National Institutes of Health, Bethesda, MD.
Jazyk:	angličtina
Zdroj:	Blood advances [Blood Adv] 2024 Jan 09; Vol. 8 (1), pp. 172-182.
DOI:	10.1182/bloodadvances.2023011542
Abstrakt:	Abstract: Data from a small trial in patients with cancer suggest that isoquercetin (IQ) treatment lowered thrombosis biomarkers and prevented clinical thrombosis, but, to our knowledge, no studies of IQ have been conducted to target thromboinflammation in adults with sickle cell disease (SCD). We conducted a randomized, double-blind, placebo-controlled trial in adults with steady-state SCD (hemoglobin SS [HbSS], HbSβ0thal, HbSβ+thal, or HbSC). The primary outcome was the change in plasma soluble P-selectin (sP-selectin) after treatment compared with baseline, analyzed in the intention-to-treat population. Between November 2019 and July 2022, 46 patients (aged 40 ± 11 years, 56% female, 75% under hydroxyurea treatment) were randomized to receive IQ (n = 23) or placebo (n = 23). IQ was well tolerated and all the adverse events (AEs; n = 21) or serious AEs (n = 14) recorded were not attributable to the study drug. The mean posttreatment change for sP-selectin showed no significant difference between the treatment groups (IQ, 0.10 ± 6.53 vs placebo, 0.74 ± 4.54; P = .64). In patients treated with IQ, whole-blood coagulation (P = .03) and collagen-induced platelet aggregation (P = .03) were significantly reduced from the baseline. Inducible mononuclear cell tissue factor gene expression and plasma protein disulfide isomerase reductase activity were also significantly inhibited (P = .003 and P = .02, respectively). Short-term fixed-dose IQ in patients with SCD was safe with no off-target bleeding and was associated with changes from the baseline in the appropriate direction for several biomarkers of thromboinflammation. The trial was registered at www.clinicaltrials.gov as #NCT04514510. (Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution.)
Databáze:	MEDLINE
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