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

NCT01722669 | Completed Early Phase 1 Results DMC FDA Drug

• 1 other identifier: 2012P000022
• Study Type: interventional
• Target: 38
• Locations: 1 country
• Sites: 1

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

Conditions

Healthy

Keywords

quercetin; isoquercetin; pharmacokinetic; pharmacodynamic

Outcome Measures

Primary Outcomes (1)

• 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)

  24 hours

Secondary Outcomes (2)

• Reductase Activity of PDI Using Dieosin Glutathione Disulfide

  2 hours. Not measured in D

• Platelet-induced Thrombin Generation (U/mL)

  4 hours

Study Arms (2)

Quercetin

EXPERIMENTAL

Single dose of quercetin with or without ascorbic acid

Drug: isoquercetin or quercetin

Isoquercetin

ACTIVE COMPARATOR

Single dose of isoquercetin with or without ascorbic acid

Drug: isoquercetin or quercetin

Interventions

isoquercetin or quercetin DRUG

Single dose PK/PD study

Isoquercetin; Quercetin

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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

Sponsors & Collaborators

• Beth Israel Deaconess Medical Center: lead

Study Sites (1)

Beth Israel Deaconess Medical Center

Boston, Massachusetts, 02215, United States

Location

Related Publications (1)

• 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.

  PMID: 28097231 DERIVED

MeSH Terms

Interventions

isoquercitrin; Quercetin

Intervention Hierarchy (Ancestors)

Flavonols; Flavonoids; Chromones; Benzopyrans; Pyrans; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Results Point of Contact

• Title: Jeffrey Zwicker, Division of Thrombosis and Haemostasis, Division of Hematology and Oncology
• Organization: Beth Israel Deaconess Medical Center, Harvard Medical School

jzwicker@bidmc.harvard.edu

617-667-9299

Study Officials

• Jeffrey Zwicker, MD

  Beth Israel Deaconess Medical Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor, Harvard Medical School

Study Record Dates

• First Submitted: May 10, 2012
• First Posted: November 7, 2012
• Study Start: May 1, 2012
• Primary Completion: December 1, 2019
• Study Completion: December 1, 2019
• Last Updated: October 12, 2020
• Results First Posted: October 12, 2020

Record last verified: 2020-10

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL
• Time Frame: 3 years

Locations

US (1)