Fixed Dose Flavonoid Isoquercetin on Thrombo-Inflammatory Biomarkers in Subjects With Stable Sickle Cell Disease
Condition: Sickle Cell Disease
MeSH terms: Anemia, Sickle Cell
Intervention: Isoquercetin; Placebo
Intervention description: 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.
Phase: Phase 2
Study type: Interventional
Primary purpose: Basic Science
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Enrollment: 46.0
Sex: All
Minimum age: 18 Years
Maximum age: 70 Years
Healthy volunteers: No
Keywords: Venous thrombosis; Protein disulfide isomerase; Thrombo-inflammation; HbS polymerization; P-selectin

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.
    

Eligibility criteria:

        -  INCLUSION CRITERIA:

        For enrollment onto the active phase of the study (IQ supplement vs placebo), subjects must
        meet all of the following criteria during the screening period (visit #1) which can last
        from 0-28 days prior to start of study intervention:

          -  Unequivocal diagnosis of sickle cell anemia (Hemoglobin SS or Hemoglobin SC or Beta
             Thalassemia Major or Beta Thalassemia Minor) confirmed by hemoglobin electrophoresis
             performed on patients at least 90 days after a blood transfusion if previously
             transfused, or DNA genotyping.

          -  Age 18-70 years old

          -  Steady state SCD (no acute vaso-occlusive crisis within 60 days of D0 of the study)
             and if on HU therapy, on an optimized dose for at least 30 days. For those newly
             initiated on HU therapy, the dose should be unchanged for at least 90 days.

          -  Be willing to comply with all study procedures for the duration of the study.

          -  Have provided signed written informed consent prior to performing any study procedure,
             including screening procedures.

        EXCLUSION CRITERIA:

        Subjects who meet any of the following criteria during screening will not receive the study
        intervention and will be counted toward study accrual. Screen failures will not be included
        in the analysis for statistical purposes:

          -  SCD with a recent VOC (<60 days from D0 of study).

          -  SCD with history of recent blood transfusion (<60 days from D0 of study) or exchange
             transfusion (<90 days from D0 of study).

          -  SCD with a recent VTE (within 90 days of diagnosis of either DVT, PE or both).

          -  Any patient receiving crizanlizumab therapy for SCD or that has received crizanlizumab
             within the past 30 days of D0 of study.

          -  Have a significant medical condition that confers an unacceptable risk to
             participating in the study, and/or that could confound the interpretation of the study
             data. Such significant medical conditions include, but are not limited to the
             following:

               1. History of recent (within 3 months prior to signing informed consent) congestive
                  heart failure; myocardial infarction or unstable angina pectoris; hemorrhagic,
                  embolic, or thrombotic stroke.

               2. Active infection requiring the use of parenteral antimicrobial agents or Grade
                  greater than or equal to 3 in severity (per National Cancer Institute Common
                  Terminology Criteria for Adverse Events v5.0) within 2 months prior to the first
                  dose of study drug.

               3. Active viral infection as evidenced by testing positive for hepatitis B surface
                  antigen or hepatitis C virus (HCV) antibody (Ab) with signs of active hepatitis B
                  or C virus infection. If the subject is positive for HCV Ab, a reverse
                  transcriptase-polymerase chain reaction test will be conducted. Subjects with
                  hepatitis C may be rescreened after receiving appropriate hepatitis C treatment.

               4. Testing positive for human immunodeficiency virus (HIV) 1 or 2 Ab with evidence
                  for ongoing active infection (i.e., CD4 count <400/microL and viral load >100,000
                  copies/mL) on antiretroviral therapy.

               5. Active acute inflammatory disorders rheumatoid arthritis or systemic lupus
                  erythematosus on disease modifying therapy.

               6. Diabetes mellitus judged to be under poor control by the Investigator evidenced
                  by a single fasting sugar value >250 gm/dl or requiring >3 antidiabetic agents,
                  including insulin (all insulins are considered 1 agent); use of insulin per se is
                  not exclusionary.

               7. History of any primary malignancy, with the exception of curatively treated
                  nonmelanomatous skin cancer; curatively treated cervical or breast carcinoma in
                  situ; or other primary tumor treated with curative intent, no known active
                  disease present, and no treatment administered during the last 3 years.

               8. Any injury or medical condition that, in the judgement of the Investigator would
                  prevent the subject from participating in the study.

          -  Have a prior bone marrow or stem cell transplant.

        INCLUSION OF VULNNERABLE PARTICIPANTS:

        Vulnerable subjects will not be included in this study.