Intervention: Isoquercetin
Trial phase: Phase 2
SMILES: O=c1c(O[C@@H]2O[C@H](CO)[C@@H](O)[C@H](O)[C@H]2O)c(-c2ccc(O)c(O)c2)oc2cc(O)cc(O)c12
Sex: All
Age groups: Adult | Older Adult
Healthy volunteers: No
Participants at risk: 23
Group description: Isoquercetin given 1000 mg, once daily by mouth for 28 days in participants with Sickle Cell Disease.
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:

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.
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.
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.
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.
Active acute inflammatory disorders rheumatoid arthritis or systemic lupus erythematosus on disease modifying therapy.
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.
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.
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.