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

Study point of contact

Jennifer L Brooks, R.N.
(301) 480-6149
[email protected]

Locations

1 United States site

Age

18 to 70 Years

Genotypes

SS, SC

Phase

Phase 2

Study type

Interventional

Gender

All

Interventions

Drug

Compensation

Unknown

About the study

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 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.

participation requirements

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 a stable dose for at least 90 days.

– Steady state SCD patient with a previous history of VTE, and/or those receiving
anticoagulant/antiplatelet therapy are eligible, so long as the VTE occurred >90 days
prior to D0 of the study.

– 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.

participation restrictions

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:

– Severe SCD defined as frequent (>6/year) or severe (requiring hospitalization >14
days) vaso-occlusive crisis.

– 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.

Locations

  • Bethesda, Maryland, United States, National Institutes of Health Clinical Center, 20892 [Recruiting]