Fixed Dose Flavonoid Isoquercetin on Thrombo-Inflammatory Biomarkers in Subjects With Stable Sickle Cell Disease
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|ClinicalTrials.gov Identifier: NCT04514510|
Recruitment Status : Recruiting
First Posted : August 17, 2020
Last Update Posted : May 19, 2022
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.
To see how Isoquercetin works in people with SCD.
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).
Participants will be screened with a physical exam, medical history, medicine review, and blood tests.
Participants may have a peripheral arterial tonometry (Endo-Pat) test to check the function of their blood vessels. For this, a thimble-shaped cup is placed on their finger and a blood pressure cuff is placed on their arm.
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 will take folic acid once a day.
Participants will have an end-of-study visit. They will discuss any side effects and repeat some of the screening tests. They may have an Endo-Pat test.
About a month after the last study 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 blood tests.
Participation will last from 8 to 12 weeks.
|Condition or disease||Intervention/treatment||Phase|
|VTE||Drug: Isoquercetin Drug: Placebo||Phase 2|
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, retinopathy and other end-organ damage. The current scientific literature currently recognizes the contribution of an acquired hypercoagulable state in SCD to vascular pathobiology, chronic organ dysfunction, and mortality.
Similar to cancer, sickle cell disease is associated with an acquired hypercoagulable state and exhibits a high prevalence of incident and recurrent venous thromboembolism (VTE). Elevated levels of the procoagulant protein tissue factor and its activator, protein disulfide isomerase in humans with SCD suggest a causal role for thrombogenesis. In cancer patients, pharmacological inhibition of plasma PDI with Isoquercetin (IQ) led to a reduction in VTE biomarkers and VTE recurrence. These findings provide support to test the hypothesis that Isoquercetin in sickle cell disease would diminish thrombo-inflammatory VTE biomarkers and attenuate the associated hypercoagulable state.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||60 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||Triple (Participant, Care Provider, Investigator)|
|Primary Purpose:||Basic Science|
|Official Title:||A Study to Evaluate the Effects of Fixed Dose Flavonoid Isoquercetin on Thrombo-Inflammatory Biomarkers in Subjects With Stable Sickle Cell Disease|
|Actual Study Start Date :||November 2, 2020|
|Estimated Primary Completion Date :||September 30, 2022|
|Estimated Study Completion Date :||October 28, 2022|
Subjects with sickle cell disease; Isoquercetin 1000mg once daily 28 days.
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.
Placebo Comparator: Placebo
Subjects with sickle cell disease; placebo once daily for 28 days.
Silicified microcrystalline cellulose NF, Ascorbic acid, Nicotinic acid, Mg stearate, Silica and Colloidal Anhydrous Ph. Eur./Colloidal Silicon dioxide USP/NF
- The primary outcome will be the change in the plasma soluble P-selectin level comparing the baseline to IQ response [ Time Frame: 28 days ]The primary outcome will be the change in plasma soluble P-selectin level comparing the baseline versus IQ or placebo.
- plasma protein disulfide isomerase activity [ Time Frame: 28 days ]Compare baseline and end of study plasma protein disulfide isomerase activity
- tissue factor positive extracellular vesicle number [ Time Frame: 28 days ]Compare baseline and end of study plasma tissue factor positive extracellular vesicle number
- procoagulant activity [ Time Frame: 28 days ]Compare baseline and end of study plasma tissue factor procoagulant activity
- inflammation and coagulation parameters [ Time Frame: 28 days ]Compare baseline and end of study inflammation and coagulation parameters
- biomarkers of vascular function and atherothrombosis [ Time Frame: 28 days ]Compare baseline and end of study contemporary biomarkers of vascular function and atherothrombosis
- safety/tolerability and adherence to oral IQ [ Time Frame: 28 days ]Assess safety/tolerability and adherence to oral IQ
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04514510
|Contact: Mai Hill, R.N.||(301) email@example.com|
|Contact: Arun S Shet, M.D.||(301) firstname.lastname@example.org|
|United States, Maryland|
|National Institutes of Health Clinical Center||Recruiting|
|Bethesda, Maryland, United States, 20892|
|Contact: For more information at the NIH Clinical Center contact Office of Patient Recruitment (OPR) 800-411-1222 ext TTY8664111010 email@example.com|
|Principal Investigator:||Arun S Shet, M.D.||National Heart, Lung, and Blood Institute (NHLBI)|