NCT04514510

Fixed Dose Flavonoid Isoquercetin on Thrombo-Inflammatory Biomarkers in Subjects With Stable Sickle Cell Disease

A Study to Evaluate the Effects of Fixed Dose Flavonoid Isoquercetin on Thrombo-Inflammatory Biomarkers in Subjects With Stable Sickle Cell Disease

• Status: Completed
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 46 (actual)
• Sponsor: National Heart, Lung, and Blood Institute (NHLBI) · NIH
• Sex: All
• Age: 18 Years – 70 Years
• Healthy volunteers: Not accepted

Summary

Background: Sickle cell disease (SCD) is an inherited hemoglobin disorder. People with SCD have an increased chance for getting blood clots. Researchers want to see if a dietary supplement called isoquercetin can decrease levels of inflammation and blood clotting in people with SCD. Objective: To see how isoquercetin works in people with SCD. Eligibility: Adults age 18-70 years old who have SCD and are in a steady-state (have not experienced a pain crisis in the last 60 days and, if taking hydroxyurea, have not had a dose change in the past 90 days). Design: Participants will be screened with a physical exam, medical history, medicine review, and blood tests. Participants will be put in 1 of 2 treatment groups. They will take 4 capsules of isoquercetin or placebo all at once, by mouth, every day for 4 weeks. They will get a pill dispenser and keep a medicine diary. Participants may have an optional near infrared spectroscopy (NIRS) test to measure how treatment affects blood flow. In this test, probes will be placed on the skin to measure tissue oxygen level and blood flow. A blood pressure cuff placed on the arm will be filled with air briefly to restrict the blood flow in the arm (for up to 5 minutes) and then released. Participants may also be asked to breathe at a certain rate or hold their breath for as long as they can during measurements. Participants will take folic acid once a day. Participants will have an end-of-study drug visit. They will discuss any side effects and repeat some of the screening tests. They may have an additional optional NIRS test. About a month after the end of study drug visit, participants will be contacted by phone to see if they have any side effects. Those who do may have a follow-up visit. At this visit, they may have additional blood tests performed. Participation will last from 8 to 12 weeks.

Detailed description

Sickle Cell Disease (SCD) is an inherited monogenic hemoglobin disorder caused by a mutation in the gene encoding the beta globin subunit of adult hemoglobin (HbA) resulting in a substitution of valine for glutamic acid at position 6 and thus producing hemoglobin S (HbS). When deoxygenated, HbS polymerizes, rendering the red cell rigid, viscous, and abnormally adherent to the capillary endothelium. This impedes blood flow in the microcirculation, causing ischemia and microinfarcts that lead to painful crises, cerebrovascular stroke, renal impairment, venous blood clots, retinopathy and other end-organ damage. The current scientific literature recognizes the contribution of an acquired hypercoagulable state in SCD to vascular pathobiology, chronic organ dysfunction, and mortality. Like cancer, SCD is associated with a hypercoagulable state and patients have a high risk of new onset and recurrent venous thromboembolism (VTE). Elevated blood levels of the procoagulant protein tissue factor and its activator, protein disulfide isomerase (PDI) in patients with SCD suggest a causal role for these proteins in the development of venous blood clots. In cancer patients, inhibiting plasma PDI activity with isoquercetin (IQ) led to a significant reduction in VTE biomarkers (soluble P-selectin and D-dimer) and venous thrombosis over the short term. These findings provide support to test the hypothesis that isoquercetin treatment in sickle cell disease would diminish thrombo-inflammatory biomarkers and attenuate the hypercoagulable state.

Conditions

• Sickle Cell Disease

Interventions

Type	Name	Description
DRUG	Isoquercetin	Isoquercetin (quercetin-3-O-beta-D-glucoside, also referred to as isoquercitrin) is a naturally occurring monoglucoside of the most studied and widely consumed bioflavonoid, quercetin. Isoquercetin given at 1000 mg, once daily by mouth for 28 days.
DRUG	Placebo	Silicified microcrystalline cellulose NF, Ascorbic acid, Nicotinic acid, Mg stearate, Silica and Colloidal Anhydrous Ph. Eur./Colloidal Silicon dioxide USP/NF. Placebo give at 1000 mg, once daily by mouth for 28 days.

Timeline

• Start date: 2020-11-02
• Primary completion: 2022-06-13
• Completion: 2022-07-07
• First posted: 2020-08-17
• Last updated: 2024-01-02
• Results posted: 2023-06-27

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study