Sickle Cell-Beta0-Thalassemia, Sickle Cell Disease
Conditions
Keywords
Sickle Cell Disease, Sickle Cell-Beta0-Thalassemia, isoquercetin
Brief summary
This research study is being done to assess the safety and effectiveness of isoquercetin to reduce levels of soluble P-Selectin in patients with sickle cell disease. Isoquercetin is a naturally occurring flavonoid-or vitamin. You will find quercetin and isoquercetin in fruits and vegetables. The names of the study drug involved in this study are/is: \- Isoquercetin
Detailed description
This is a single-arm phase 2 study in adults with Sickle Cell Disease (SCD) to assess the effect of oral isoquercetin on biomarkers of endothelial and platelet activation, inflammation and ongoing blood coagulation. * The research study procedures include screening for eligibility and study treatment including evaluations and follow up visits. * The names of the study drug involved in this study are/is: Isoquercetin * Participants will receive study treatment for 1 year and will be followed for 30 days after the last dose. * This research study is a Phase II clinical trial. Phase II clinical trials test the safety and effectiveness of an investigational drug to learn whether the drug works in treating a specific disease. Investigational means that the drug is being studied. * The U.S. Food and Drug Administration (FDA) has not approved isoquercetin as a treatment for any disease.
Interventions
DRUGIsoquercetin
Oral, 1 time per day, per predetermined dosed per 28 treatment cycle.
Sponsors
Quercegen Pharmaceuticals
Jeffrey Zwicker, MD
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 50 Years
Healthy volunteers
Yes
Inclusion criteria
* Eligible subjects require an established diagnosis of sickle cell disease/homozygous hemoglobin S (SCD-SS) or sickle cell disease hemoglobin β0-thalassemia (SCD-Sβ0-thal). * Patients on other therapy including hydroxyurea will be included. * Age 18-50 years. * Participants must have preserved organ and marrow function as defined below: * leukocytes ≥2,000/mcL * platelets ≥75,000/mcL * AST(SGOT)/ALT(SGPT) ≤2.5 × institutional upper limit of normal * Estimated creatinine clearance ≥45 mL/min/1.73 m2 for participants with creatinine levels above institutional normal. * Subjects with no evidence of worsening over the last 4 weeks (e.g. any acute complication of SCD including but not limited to VOC, acute chest syndrome and stroke, that required unscheduled medical attention or intervention) as determined by the investigator will be included. * Patients on anticoagulation therapy will be excluded. * The effects of isoquercetin on the developing human fetus are unknown. For this reason, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately. Men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and 4 months after completion of isoquercetin administration. * Ability to understand and the willingness to sign a written informed consent document
Exclusion criteria
* Please ensure
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in sP Selectin levels with isoquercetin | baseline to 28 Days | Comparisons between baseline and follow-up measurements (i.e. change in sP-Selectin), will be performed using a two-tailed, paired t-test analyses. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Platelet dependent thrombin generation (coagulation) | baseline to 1 year | Laboratory values at baseline and subsequent monthly follow-up time points will be modeled using linear mixed effects regression with an autoregressive covariance structure. |
| sE-selectin (adhesion)-Biomarker | baseline to 1 year | Laboratory values at baseline and subsequent monthly follow-up time points will be modeled using linear mixed effects regression with an autoregressive covariance structure. |
| C-reactive protein CRP | baseline to 1 year | Laboratory values at baseline and subsequent monthly follow-up time points will be modeled using linear mixed effects regression with an autoregressive covariance structure. |
| Number of Participants With Treatment-Related Adverse Events | start of study treatment up to 13 months | Sickle cell events such as SCPC, uncomplicated pain crisis, hospitalizations, emergency room visits, transfusions, acute chest syndrome and transfusion support will be summarized as annualized numbers. Statistical comparisons will be made for each patient relative to the number from the previous year using a Wilcoxon rank-sum test. |
Outcome results
None listed