Working…
COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC: https://www.coronavirus.gov.

Get the latest research information from NIH: https://www.nih.gov/coronavirus.
ClinicalTrials.gov
ClinicalTrials.gov Menu

Isoquercetin in Sickle Cell Anemia

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04474626
Recruitment Status : Not yet recruiting
First Posted : July 17, 2020
Last Update Posted : July 17, 2020
Sponsor:
Collaborator:
Quercegen Pharmaceuticals
Information provided by (Responsible Party):
Jeffrey Zwicker, MD, Beth Israel Deaconess Medical Center

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


Condition or disease Intervention/treatment Phase
Sickle Cell Disease Sickle Cell-Beta0-Thalassemia Drug: Isoquercetin Phase 2

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.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 20 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Single-arm Phase 2 Study of Oral Isoquercetin in Sickle Cell Disease
Estimated Study Start Date : September 2020
Estimated Primary Completion Date : December 31, 2022
Estimated Study Completion Date : December 31, 2024

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: ISOQUERCETIN

The research study procedures include screening for eligibility and study treatment including evaluations and follow up visits

- ISOQUERCETIN: Oral Study Drug, 1 time per day, per predetermined dosed per 28 treatment cycle.

This will continue for up to 337 days.

Drug: Isoquercetin
Oral, 1 time per day, per predetermined dosed per 28 treatment cycle.
Other Name: IQC-950AN




Primary Outcome Measures :
  1. Change in sP Selectin levels with isoquercetin [ Time Frame: 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 Outcome Measures :
  1. Platelet dependent thrombin generation (coagulation) [ Time Frame: 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.

  2. sE-selectin (adhesion)-Biomarker [ Time Frame: 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.

  3. C-reactive protein CRP [ Time Frame: 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.

  4. Number of Participants With Treatment-Related Adverse Events [ Time Frame: 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.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years to 50 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

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 exclusion criteria are clearly worded to describe participants who will not be eligible.
  • Participants may not be concurrently receiving any other study agents.
  • Subjects with no evidence of worsening over the last 1 month (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.
  • Familial bleeding diathesis.
  • Known diagnosis of disseminated intravascular coagulation.
  • Currently receiving anticoagulant therapy.
  • Currently using daily use of aspirin (>81mg daily), Clopidogrel (Plavix), cilostazol (Pletal), aspirin-dipyridamole (Aggrenox) (within 10 days)
  • History of allergic reactions attributed to compounds of similar chemical or biologic composition to isoquercetin.
  • Uncontrolled intercurrent illness including but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina, cardiac arrhythmia, or psychiatric illness/social situations that would limit study compliance.
  • Pregnant women are excluded from this study because isoquercetin is a PDI inhibitor with the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk of adverse events in nursing infants secondary to treatment of the mother with isoquercetin, breastfeeding should be discontinued if the mother is treated with isoquercetin. These potential risks may also apply to other agents used in this study.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04474626


Contacts
Layout table for location contacts
Contact: Jeffrey Zwicker, MD 617-667-9299 jzwicker@bidmc.harvard.edu

Locations
Layout table for location information
United States, Massachusetts
Brigham and Women's Hospital
Boston, Massachusetts, United States, 02115
Contact: Maureen Achebe, MD    617-732-5048    machebe@bwh.harvard.edu   
Principal Investigator: Maureen Achebe, MD         
Massachusetts General Hospital
Boston, Massachusetts, United States, 02115
Contact: David Kuter, MD    617-726-8743      
Principal Investigator: David Kuter, MD         
Beth Israel Deaconess Medical Center
Boston, Massachusetts, United States, 02215
Contact: Jeffrey Zwicker, MD    617-667-9299    jzwicker@bidmc.harvard.edu   
Principal Investigator: Jeffrey Zwicker, MD         
Sponsors and Collaborators
Jeffrey Zwicker, MD
Quercegen Pharmaceuticals
Investigators
Layout table for investigator information
Principal Investigator: Jeffrey Zwicker, MD Beth Israel Deaconess Medical Center
Layout table for additonal information
Responsible Party: Jeffrey Zwicker, MD, Principal Investigator, Beth Israel Deaconess Medical Center
ClinicalTrials.gov Identifier: NCT04474626    
Other Study ID Numbers: 20-087
First Posted: July 17, 2020    Key Record Dates
Last Update Posted: July 17, 2020
Last Verified: July 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: The Dana-Farber / Harvard Cancer Center encourages and supports the responsible and ethical sharing of data from clinical trials. De-identified participant data from the final research dataset used in the published manuscript may only be shared under the terms of a Data Use Agreement. Requests may be directed to Sponsor Investigator or designee. The protocol and statistical analysis plan will be made available on Clinicaltrials.gov only as required by federal regulation or as a condition of awards and agreements supporting the research.
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Informed Consent Form (ICF)
Time Frame: Data can be shared no earlier than 1 year following the date of publication
Access Criteria: BIDMC - Contact the Beth Israel Deaconess Medical Center Technology Ventures Office at tvo@bidmc.harvard.edu

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Jeffrey Zwicker, MD, Beth Israel Deaconess Medical Center:
Sickle Cell Disease
Sickle Cell-Beta0-Thalassemia
isoquercetin
Additional relevant MeSH terms:
Layout table for MeSH terms
Anemia, Sickle Cell
Thalassemia
Anemia, Hemolytic, Congenital
Anemia, Hemolytic
Anemia
Hematologic Diseases
Hemoglobinopathies
Genetic Diseases, Inborn