Fixed Dose Flavonoid Isoquercetin on Thrombo-Inflammatory Biomarkers in Subjects With Stable Sickle Cell Disease
Condition: Sickle Cell Disease
MeSH terms: Anemia, Sickle Cell
Study type: Interventional
Phase: Phase 2

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.
    

Intervention name(s): Isoquercetin; Placebo
Intervention type(s): Drug; Drug
Intervention description(s): 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.; 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.
Other intervention name(s): isoquercitrin
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary purpose: Basic Science
Keywords: Venous thrombosis; Protein disulfide isomerase; Thrombo-inflammation; HbS polymerization; P-selectin