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Quercetin PK/PD Study in Healthy Adults and Patients With Hypercoagulable States (PK/PD)

Primary Purpose

Healthy

Status
Completed
Phase
Early Phase 1
Locations
United States
Study Type
Interventional
Intervention
isoquercetin or quercetin
Sponsored by
Beth Israel Deaconess Medical Center
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional basic science trial for Healthy focused on measuring quercetin, isoquercetin, pharmacokinetic, pharmacodynamic

Eligibility Criteria

18 Years - 80 Years (Adult, Older Adult)All SexesAccepts Healthy Volunteers

Inclusion Criteria

  • Subject is willing to participate and provide informed consent
  • Subject is considered reliable and capable of adhering to the protocol per the judgment of the Investigator

  • Subjects in group D must exhibit good organ reserves (within prior 4 weeks) defined as:

    1. Estimated GFR >35 (formula),
    2. Platelet count >65 K/uL,
    3. Hemoglobin >10.5 grams/dL
    4. Total bilirubin <2.0 mg/dL
  • Minimum age 18 years old
  • Body mass index (BMI) between 18 and 35 kg/m2
  • For cohort D (antiphospholipid antibodies) a. Subjects in group D must have at least one positive antiphospholipid antibody within the last 8 weeks and/or previous confirmed antibodies (2 or more occasions at least 12 weeks apart) : i. Positive lupus anticoagulant ii. anticardiolipin antibody IgM or IgG (>40U GPL) iii. anti-β2 Glycoprotein1 antibody titer (>35 units)

Exclusion Criteria

  • Pregnant. If female of child-bearing age, negative urinary pregnancy test prior to dosing of quercetin or isoquercetin
  • No history of malabsorptive gastrointestinal disorder

  • Currently taking aspirin, NSAIDS, warfarin, low-molecular weight heparin or other anticoagulants (such as direct thrombin inhibitors or factor X inhibitors)

    a. Note: Study subjects taking aspirin or NSAIDS, if treating physician concurs, are permitted to enroll if plan to hold for aspirin 10 days or NSAIDS 24 hours prior to dosing of quercetin/isoquercetin

  • Prescribed niacin for hyperlipidemia
  • Known HIV
  • History of sensitivity or intolerance to flavonoids, niacin or ascorbic acid
  • May not have uncontrolled intercurrent illness including, but not limited to ongoing or active infection, hepatitis, symptomatic congestive heart failure, unstable angina pectoris or cardiac arrhythmia

Sites / Locations

  • Beth Israel Deaconess Medical Center

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Quercetin

Isoquercetin

Arm Description

Single dose of quercetin with or without ascorbic acid

Single dose of isoquercetin with or without ascorbic acid

Outcomes

Primary Outcome Measures

AUC
AUC 0-24 hours of measured plasma quercetin aglycone for Arms A1, B1, A2, B2, C Collected at timepoints: baseline and 1, 2, 4, 6, 8, and 24 hours after dose. PK and PDI samples were not measured for Arm D (anti-phospholipid antibody cohort)

Secondary Outcome Measures

Reductase Activity of PDI Using Dieosin Glutathione Disulfide
Measurement of protein disulfide inhibition in plasma using a fluorescent PDI substrate (dieosin glutathione disulfide)
Platelet-induced Thrombin Generation (U/mL)
Thrombin induced thrombin generation measured in patient plasma

Full Information

First Posted
May 10, 2012
Last Updated
October 9, 2020
Sponsor
Beth Israel Deaconess Medical Center
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1. Study Identification

Unique Protocol Identification Number
NCT01722669
Brief Title
Quercetin PK/PD Study in Healthy Adults and Patients With Hypercoagulable States
Acronym
PK/PD
Official Title
Pharmacokinetic and Pharmacodynamic Study of Oral Quercetin and Isoquercetin in Healthy Adults and Patients With Hypercoagulable States.
Study Type
Interventional

2. Study Status

Record Verification Date
October 2020
Overall Recruitment Status
Completed
Study Start Date
May 2012 (undefined)
Primary Completion Date
December 2019 (Actual)
Study Completion Date
December 2019 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Beth Israel Deaconess Medical Center

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
The goal of this study is to evaluate how much quercetin or isoquercetin is absorbed after a single dose and evaluate for pharmacokinetic inhibition of protein disulfide isomerase. Pharmacodynamic studies will also be performed in an additional cohort of 10 patients with evidence of antiphospholipid antibodies
Detailed Description
To compare the absorption and activity of quercetin or isoquercetin with or without ascorbic acid in healthy adults. Oral chews containing quercetin (500mg) or isoquercetin(500 mg total) with or without ascorbic acid will be given. Pharmacokinetic parameters (AUC, Cmax, Tmax, elimination half-life) will be determined over 24 hours (8 time points). Pharmacodynamic inhibition of protein disulfide isomerase activity will also be assessed. In addition to healthy subjects, a cohort of 10 individuals with antiphospholipid antibodies will participate. These participants will receive isoquercetin 1000 mg and have pharmacodynamics studies performed at time 0 and 4 hours. All study drugs will be provided by Quercegen Pharma.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Healthy
Keywords
quercetin, isoquercetin, pharmacokinetic, pharmacodynamic

7. Study Design

Primary Purpose
Basic Science
Study Phase
Early Phase 1
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
38 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Quercetin
Arm Type
Experimental
Arm Description
Single dose of quercetin with or without ascorbic acid
Arm Title
Isoquercetin
Arm Type
Active Comparator
Arm Description
Single dose of isoquercetin with or without ascorbic acid
Intervention Type
Drug
Intervention Name(s)
isoquercetin or quercetin
Intervention Description
Single dose PK/PD study
Primary Outcome Measure Information:
Title
AUC
Description
AUC 0-24 hours of measured plasma quercetin aglycone for Arms A1, B1, A2, B2, C Collected at timepoints: baseline and 1, 2, 4, 6, 8, and 24 hours after dose. PK and PDI samples were not measured for Arm D (anti-phospholipid antibody cohort)
Time Frame
24 hours
Secondary Outcome Measure Information:
Title
Reductase Activity of PDI Using Dieosin Glutathione Disulfide
Description
Measurement of protein disulfide inhibition in plasma using a fluorescent PDI substrate (dieosin glutathione disulfide)
Time Frame
2 hours. Not measured in D
Title
Platelet-induced Thrombin Generation (U/mL)
Description
Thrombin induced thrombin generation measured in patient plasma
Time Frame
4 hours

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria Subject is willing to participate and provide informed consent Subject is considered reliable and capable of adhering to the protocol per the judgment of the Investigator Subjects in group D must exhibit good organ reserves (within prior 4 weeks) defined as: Estimated GFR >35 (formula), Platelet count >65 K/uL, Hemoglobin >10.5 grams/dL Total bilirubin <2.0 mg/dL Minimum age 18 years old Body mass index (BMI) between 18 and 35 kg/m2 For cohort D (antiphospholipid antibodies) a. Subjects in group D must have at least one positive antiphospholipid antibody within the last 8 weeks and/or previous confirmed antibodies (2 or more occasions at least 12 weeks apart) : i. Positive lupus anticoagulant ii. anticardiolipin antibody IgM or IgG (>40U GPL) iii. anti-β2 Glycoprotein1 antibody titer (>35 units) Exclusion Criteria Pregnant. If female of child-bearing age, negative urinary pregnancy test prior to dosing of quercetin or isoquercetin No history of malabsorptive gastrointestinal disorder Currently taking aspirin, NSAIDS, warfarin, low-molecular weight heparin or other anticoagulants (such as direct thrombin inhibitors or factor X inhibitors) a. Note: Study subjects taking aspirin or NSAIDS, if treating physician concurs, are permitted to enroll if plan to hold for aspirin 10 days or NSAIDS 24 hours prior to dosing of quercetin/isoquercetin Prescribed niacin for hyperlipidemia Known HIV History of sensitivity or intolerance to flavonoids, niacin or ascorbic acid May not have uncontrolled intercurrent illness including, but not limited to ongoing or active infection, hepatitis, symptomatic congestive heart failure, unstable angina pectoris or cardiac arrhythmia
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jeffrey Zwicker, MD
Organizational Affiliation
Beth Israel Deaconess Medical Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
Beth Israel Deaconess Medical Center
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02215
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing Plan Description
Contact PI
IPD Sharing Time Frame
3 years
Citations:
PubMed Identifier
28097231
Citation
Stopa JD, Neuberg D, Puligandla M, Furie B, Flaumenhaft R, Zwicker JI. Protein disulfide isomerase inhibition blocks thrombin generation in humans by interfering with platelet factor V activation. JCI Insight. 2017 Jan 12;2(1):e89373. doi: 10.1172/jci.insight.89373.
Results Reference
derived

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Quercetin PK/PD Study in Healthy Adults and Patients With Hypercoagulable States

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