Phase 2
N=46
Fixed Dose Flavonoid Isoquercetin on Thrombo-Inflammatory Biomarkers in Subjects With Stable Sickle Cell Disease
Sickle Cell Disease
Bottom Line
View on ClinicalTrials.gov: NCT04514510 ↗Enrolled (actual)
46
Serious AEs
21.7%
Results posted
Jun 2023
Primary outcome: Primary: Mean Change in the Plasma Soluble P-selectin Level — 0.74; 0.10 ng/ml — p=0.64
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 2
- Interventions
- Isoquercetin (Drug); Placebo (Drug)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- All
- Sponsor
- National Heart, Lung, and Blood Institute (NHLBI)
- Primary completion
- Jun 2022
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Mean Change in the Plasma Soluble P-selectin Level |
0.74; 0.10 | 0.64 |
| SECONDARY Mean Change in Plasma Protein Disulfide Isomerase Activity |
-3.13; 1.95 | — |
| SECONDARY Median Change of Tissue Factor Vesicle Number |
39; -382 | — |
| SECONDARY Mean Change in Tissue Factor Vesicle Procoagulant Activity |
-427; -43 | — |
| SECONDARY Mean Change in D-Dimer |
0.15; 0.28 | — |
| SECONDARY Mean Change in Vascular Cell Adhesion Molecule |
-22.43; -38.15 | — |
| SECONDARY Median Relative Blood Flow Index (rBFI) Determined by Near-infrared Spectroscopy (NIRS) |
0.00000000082; 0.00000000037 | 0.149 |
| SECONDARY Mean Percent Adherence to Study Drug |
96.2; 97.2 | — |
| SECONDARY Number of Adverse Events Grade 2 and Above |
8; 9; 1; 2; 8; 6 | — |
| SECONDARY Number of Participants That Tolerated Study Drug |
22; 22 | — |
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 ( 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.
Data sourced from ClinicalTrials.gov (NCT04514510). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.