A Comparison of Fisetin Kinetics in Young and Old Adults

NCT ID: NCT06796374

Last Updated: 2025-01-28

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Clinical Phase: NA
• Total Enrollment: 80 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-02-01
• Study Completion Date: 2026-07-31

Brief Summary

This study investigates the differences in the kinetic parameters of fisetin in two cohorts of healthy volunteers:

Cohort 1) volunteers aged 18-30 years (n = 40) Cohort 2) volunteers aged 65 years or older (n = 40)

The purpose of this study is:

1. To describe the fisetin kinetics after a single dose oral administration in older age.

2. To compare the fisetin kinetics after a single dose oral administration in old and young age.

FISEKIN-1 is designed as a four-arm study protocol. As well as two different age groups (18-30 years vs. 65 years and older), we want to compare fisetin kinetic parameters in two different fisetin formulations and dosages :

Arm 1) 100 mg fisetin (1x 1 capsule), cohort 1: young age Arm 2) 100 mg fisetin (1x 1 capsule), cohort 2: old age Arm 3) 1000 mg fisetin + 200 mg quercetin (2x 1 softgel capsule), cohort 1: young age Arm 4) 1000 mg fisetin + 200 mg quercetin (2x 1 softgel capsule), cohort 2: old age

Detailed Description

The study is designed as an open-label, two-cohorts (young vs. old), four-arm, cross-over, single oral dose protocol.

A single oral dose of fisetin will be administered as capsules with 240 ml of still water in the overnight fasting condition.

Both arms will be conducted in each participant in random order with a wash-out period of at least one week between each arm.

A total of 18 blood samples will be taken at defined time points (baseline; 10; 20; 30; 40; 50; 60; 80; 100 min; 2.0; 2.5; 3.0; 4.0; 5.0; 6.0; 8.0; 10.0; 24.0 h). At each time point, blood will be collected (4.9 ml for separation of plasma) to determine fisetin, its metabolites, and quercetin (only in arm 3 and 4).

The total amount of blood collected for each participant and each arm is 90 ml at the kinetic visits and 12 ml at the screening visit.

After intake of fisetin, participants will drink 200 ml of sparkling water every hour to stimulate gastrointestinal peristalsis and to promote transport of the capsule. After 2 hours, the participants may drink a cup of tea or coffee and after 4 hours they will be served a meal low in fisetin content. Urine will be collected during the first 10 hours after fisetin administration. Monitoring of blood pressure and heart rate will take place for the first 4 hours after administration. Volunteers will stay in the Clinical Research Unit of the Institute of Pharmacology for the first 10 hours after administration.

Conditions

Pharmacokinetic Study in Healthy Volunteers

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: NONE

Study Groups

Arm 2: Fisetin - Cohort 2: old age (≥ 65 years)

Group Type: ACTIVE_COMPARATOR

Fisetin

Intervention Type: DIETARY_SUPPLEMENT

A single oral dose of 100 mg fisetin (as Novusetin®) will be administered as 1 capsule with 240 ml of still water in the overnight fasting condition:

A total of 18 blood samples will be taken at defined time points (baseline; 10; 20; 30; 40; 50; 60; 80; 100 min; 2.0; 2.5; 3.0; 4.0; 5.0; 6.0; 8.0; 10.0; 24.0 h). At each time point, blood will be collected (4.9 ml for separation of plasma) to determine fisetin, and fisetin metabolites. The total amount of blood collected for each participant and each arm is 90 ml at the kinetic visits and 12 ml at the screening visit. Urine will be collected during the first 10 hours after fisetin administration.

Arm 4: Fisetin + Quercetin - Cohort 2: old age (≥ 65 years)

Group Type: ACTIVE_COMPARATOR

Fisetin + Quercetin

Intervention Type: DIETARY_SUPPLEMENT

A single oral dose of 1000 mg fisetin + 200 mg quercetin will be administered as 2 softgel capsule with 240 ml of still water in the overnight fasting condition:

A total of 18 blood samples will be taken at defined time points (baseline; 10; 20; 30; 40; 50; 60; 80; 100 min; 2.0; 2.5; 3.0; 4.0; 5.0; 6.0; 8.0; 10.0; 24.0 h). At each time point, blood will be collected (4.9 ml for separation of plasma) to determine fisetin, fisetin metabolites, and quercetin. The total amount of blood collected for each participant and each arm is 90 ml at the kinetic visits and 12 ml at the screening visit. Urine will be collected during the first 10 hours after fisetin administration.

Arm 1: Fisetin - Cohort 1: young age (18-30 years)

Group Type: ACTIVE_COMPARATOR

Fisetin

Intervention Type: DIETARY_SUPPLEMENT

A single oral dose of 100 mg fisetin (as Novusetin®) will be administered as 1 capsule with 240 ml of still water in the overnight fasting condition:

A total of 18 blood samples will be taken at defined time points (baseline; 10; 20; 30; 40; 50; 60; 80; 100 min; 2.0; 2.5; 3.0; 4.0; 5.0; 6.0; 8.0; 10.0; 24.0 h). At each time point, blood will be collected (4.9 ml for separation of plasma) to determine fisetin, and fisetin metabolites. The total amount of blood collected for each participant and each arm is 90 ml at the kinetic visits and 12 ml at the screening visit. Urine will be collected during the first 10 hours after fisetin administration.

Arm 3: Fisetin + Quercetin - Cohort 1: young age (18-30 years)

Group Type: ACTIVE_COMPARATOR

Fisetin + Quercetin

Intervention Type: DIETARY_SUPPLEMENT

A single oral dose of 1000 mg fisetin + 200 mg quercetin will be administered as 2 softgel capsule with 240 ml of still water in the overnight fasting condition:

A total of 18 blood samples will be taken at defined time points (baseline; 10; 20; 30; 40; 50; 60; 80; 100 min; 2.0; 2.5; 3.0; 4.0; 5.0; 6.0; 8.0; 10.0; 24.0 h). At each time point, blood will be collected (4.9 ml for separation of plasma) to determine fisetin, fisetin metabolites, and quercetin. The total amount of blood collected for each participant and each arm is 90 ml at the kinetic visits and 12 ml at the screening visit. Urine will be collected during the first 10 hours after fisetin administration.

Interventions

Fisetin

A single oral dose of 100 mg fisetin (as Novusetin®) will be administered as 1 capsule with 240 ml of still water in the overnight fasting condition:

A total of 18 blood samples will be taken at defined time points (baseline; 10; 20; 30; 40; 50; 60; 80; 100 min; 2.0; 2.5; 3.0; 4.0; 5.0; 6.0; 8.0; 10.0; 24.0 h). At each time point, blood will be collected (4.9 ml for separation of plasma) to determine fisetin, and fisetin metabolites. The total amount of blood collected for each participant and each arm is 90 ml at the kinetic visits and 12 ml at the screening visit. Urine will be collected during the first 10 hours after fisetin administration.

Intervention Type: DIETARY_SUPPLEMENT

Fisetin + Quercetin

A single oral dose of 1000 mg fisetin + 200 mg quercetin will be administered as 2 softgel capsule with 240 ml of still water in the overnight fasting condition:

A total of 18 blood samples will be taken at defined time points (baseline; 10; 20; 30; 40; 50; 60; 80; 100 min; 2.0; 2.5; 3.0; 4.0; 5.0; 6.0; 8.0; 10.0; 24.0 h). At each time point, blood will be collected (4.9 ml for separation of plasma) to determine fisetin, fisetin metabolites, and quercetin. The total amount of blood collected for each participant and each arm is 90 ml at the kinetic visits and 12 ml at the screening visit. Urine will be collected during the first 10 hours after fisetin administration.

Intervention Type: DIETARY_SUPPLEMENT

Eligibility Criteria

Inclusion Criteria

• any sex
• age between 18 and 30 years or ≥ 65 years
• understands the study purpose and design
• contractually capable and provides signed informed consent form
• healthy condition or mild and/or well-treated forms of allergies, asthma, hypertension, and orthopedic diseases
• a maximum of 3 chronically taken drugs

Exclusion Criteria

• BMI > 30 kg/m2 and < 18 kg/m2
• body weight < 48 kg
• women in young cohort: known pregnancy or lactation period; positive urine pregnancy test at screening or kinetic visit
• men: hemoglobin < 13 g/dl (8,07 mmol/l) women: hemoglobin < 12 g/dl (7,45 mmol/l)
• elevated liver function tests (1 or more of ALAT, ASAT, yGT, Bilirubin > 2x ULN)
• reduced renal function (eGFRMDRD < 60 ml/min/1,7 m2)
• QTcF > 450 ms in screening ECG
• psychiatric disease requiring recent or actual treatment
• drug dependency at the time of visit
• use of recreational drugs more than twice a week
• any known hypersensitivity or allergic reactions to fisetin
• history of severe hypersensitivity reactions and/or anaphylaxis
• poor venous conditions that make it impossible to place a peripheral venous catheter and regularly draw blood through it
• intake of drugs interfering with CYP1A2, CYP2D6, CYP2C8, CYP2C9, CYP2C19, CYP3A4, and/or Pgp during the past seven days if the duration of intake was at least two days
• individuals who have eaten food with high fisetin content in the two days before the kinetic visits (e.g. strawberry, apple, persimmon, grape, mango, kiwi, peach, tomato, onion, lotus roots, kale, cucumber; processed products, e.g. wine)

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

University Medicine Greifswald

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Central Contacts

Stefan Engeli, Prof.

Role: CONTACT

stefan.engeli@med.uni-greifswald.de

+49 3834 86 56 33

Other Identifiers

IPHA-2025-010

Identifier Type: -

Identifier Source: org_study_id