Sickle Cell DiseasePhase 2NCT04474626
Isoquercetin in Sickle Cell Anemia
A Phase 2 study testing Isoquercetin in people with Sickle Cell Disease and Sickle Cell-Beta0-Thalassemia, run by Jeffrey Zwicker, MD.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 50 yearsHealthy volunteers can take part
- Conditions the study is for
- Sickle Cell Disease, Sickle Cell-Beta0-Thalassemia
- What is being tested?
- Isoquercetin
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- No sites listed yet
- Study dates
- Dec 2020to 31 Dec 2024
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 50 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- 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
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- 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
Who cannot join
- 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.
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- 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.
About this study
Official title: Single-arm Phase 2 Study of Oral Isoquercetin in Sickle Cell Disease
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
Read the 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.
- Conditions
- Sickle Cell Disease, Sickle Cell-Beta0-Thalassemia
- Being tested
- Isoquercetin
- Keywords
- Sickle Cell Disease, Sickle Cell-Beta0-Thalassemia, isoquercetin
- Medical subject headings
- Anemia, Sickle Cell
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
IsoquercetinDrug
Also called IQC-950AN
Oral, 1 time per day, per predetermined dosed per 28 treatment cycle.
| Study group | Role | What they receive |
|---|---|---|
| ISOQUERCETIN | Experimental | 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. Receives: Drug: Isoquercetin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in sP Selectin levels with isoquercetin
Comparisons between baseline and follow-up measurements (i.e. change in sP-Selectin), will be performed using a two-tailed, paired t-test analyses.
Measured: baseline to 28 Days
Secondary outcomes (4)
Platelet dependent thrombin generation (coagulation)
Laboratory values at baseline and subsequent monthly follow-up time points will be modeled using linear mixed effects regression with an autoregressive covariance structure.
Measured: baseline to 1 year
sE-selectin (adhesion)-Biomarker
Laboratory values at baseline and subsequent monthly follow-up time points will be modeled using linear mixed effects regression with an autoregressive covariance structure.
Measured: baseline to 1 year
C-reactive protein CRP
Laboratory values at baseline and subsequent monthly follow-up time points will be modeled using linear mixed effects regression with an autoregressive covariance structure.
Measured: baseline to 1 year
Number of Participants With Treatment-Related Adverse Events
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.
Measured: start of study treatment up to 13 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Jul 2020
- Study startDec 2020 (estimated)
- Primary completion31 Dec 2022 (estimated)
- Study completion31 Dec 2024 (estimated)
Why it stopped: Trial did not activate
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Sickle Cell DiseaseStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Jeffrey Zwicker, MD
- Sponsor type
- University, hospital or other
- Collaborators
- Quercegen Pharmaceuticals
- Responsible party
- Sponsor-investigator, Jeffrey Zwicker, MD, Beth Israel Deaconess Medical Center
- Investigators
- Jeffrey Zwicker, MD, Principal investigator, Beth Israel Deaconess Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04474626
- Sponsor's protocol ID
- 20-087
- Status last verified
- Jan 2021
- First submitted
- 6 Jul 2020
- Last updated
- 11 Jan 2021
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: 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.
Study at a glance
From the registry record, last updated by the sponsor on 11 Jan 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Single-arm Phase 2 Study of Oral Isoquercetin in Sickle Cell Disease
- ClinicalTrials.gov ID
- NCT04474626
- Acronym / sponsor ID
- 20-087
- Conditions
- Sickle Cell Disease, Sickle Cell-Beta0-Thalassemia
- Keywords
- Sickle Cell Disease, Sickle Cell-Beta0-Thalassemia, isoquercetin
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: Trial did not activate
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Jeffrey Zwicker, MDUniversity, hospital or other
- Collaborators
- Quercegen Pharmaceuticals
- Study start
- Dec 2020 (estimated)
- Primary completion
- 31 Dec 2022 (estimated)
- Study completion
- 31 Dec 2024 (estimated)
- First posted
- 17 Jul 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| ISOQUERCETIN | Experimental | Drug: IsoquercetinThe 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. |
Who may qualify
- Ages
- 18 to 50 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (12 listed)
- 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:
- 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.
Key exclusion criteria (10 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| IsoquercetinAlso: IQC-950ANOral, 1 time per day, per predetermined dosed per 28 treatment cycle. | Drug | ISOQUERCETIN |
Primary outcome
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.
4 secondary outcomes
Platelet dependent thrombin generation (coagulation)
Time frame: baseline to 1 year
sE-selectin (adhesion)-Biomarker
Time frame: baseline to 1 year
C-reactive protein CRP
Time frame: baseline to 1 year
Number of Participants With Treatment-Related Adverse Events
Time frame: start of study treatment up to 13 months
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Jan 2021.
- Individual participant dataSharing planned: Yes. 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Jeffrey Zwicker, MD principal investigator
Beth Israel Deaconess Medical Center
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Isoquercetin in people with Sickle Cell Disease and Sickle Cell-Beta0-Thalassemia, run by Jeffrey Zwicker, MD.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 12 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: withdrawn, as of the sponsor's last update on 11 Jan 2021. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in sP Selectin levels with isoquercetin (time frame: baseline to 28 Days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 Jan 2021.