Clinical trial NCT06796374: A Comparison of Fisetin Kinetics in Young and Old Adults
Official title: A Comparison of Fisetin Kinetics in Young and Old Adults - FISEKIN-1
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: NA
Conditions: Pharmacokinetic Study in Healthy Volunteers
Lead sponsor: University Medicine Greifswald
Sponsor class: OTHER
First posted: 2025-01-28
Enrollment: 80
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: The kinetic study will be designed as an open-label, two-cohorts (young vs. old), four-arm, randomized cross-over, single oral dose protocol.
Primary purpose: BASIC_SCIENCE

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.

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)

Primary outcomes:
measure: Fisetin plasma concentration arm 1 vs. arm 2
timeFrame: 24 hours
measure: Fisetin plasma concentration arm 3 vs. arm 4
timeFrame: 24 hours
Secondary outcomes:
measure: Fisetin metabolites plasma concentration arm 1 vs. arm 2
timeFrame: 24 hours
measure: Fisetin metabolites plasma concentration arm 3 vs. arm 4
timeFrame: 24 hours
measure: Fisetin plasma concentration arm 1 vs. arm 2
timeFrame: 24 hours
measure: Fisetin plasma concentration arm 3 vs. arm 4
timeFrame: 24 hours
measure: Fisetin plasma concentration arm 1 vs. arm 2
timeFrame: 24 hours
measure: Fisetin plasma concentration arm 3 vs. arm 4
timeFrame: 24 hours
measure: Fisetin plasma concentration arm 1 vs. arm 2
timeFrame: 24 hours
measure: Fisetin plasma concentration arm 3 vs. arm 4
timeFrame: 24 hours
measure: Fisetin plasma concentration arm 1 vs. arm 2
timeFrame: 24 hours
measure: Fisetin plasma concentration arm 3 vs. arm 4
timeFrame: 24 hours
measure: Fisetin plasma concentration arm 1 vs. arm 2
timeFrame: 24 hours
measure: Fisetin plasma concentration arm 3 vs. arm 4
timeFrame: 24 hours
measure: Fisetin plasma concentration arm 1 vs. arm 3
timeFrame: 24 hours
measure: Fisetin plasma concentration arm 2 vs. arm 4
timeFrame: 24 hours
measure: Fisetin plasma concentration arm 1 vs. arm 3
timeFrame: 24 hours
measure: Fisetin plasma concentration arm 2 vs. arm 4
timeFrame: 24 hours
measure: Fisetin plasma concentration arm 1 vs. arm 3
timeFrame: 24 hours
measure: Fisetin plasma concentration arm 2 vs. arm 4
timeFrame: 24 hours
measure: Fisetin plasma concentration arm 1 vs. arm 3
timeFrame: 24 hours
measure: Fisetin plasma concentration arm 2 vs. arm 4
timeFrame: 24 hours
measure: Fisetin plasma concentration arm 1 vs. arm 3
timeFrame: 24 hours
measure: Fisetin plasma concentration arm 2 vs. arm 4
timeFrame: 24 hours
measure: Fisetin plasma concentration arm 1 vs. arm 3
timeFrame: 24 hours
measure: Fisetin plasma concentration arm 2 vs. arm 4
timeFrame: 24 hours
measure: Quercetin plasma concentration arm 3 vs. arm 4
timeFrame: 24 hours
measure: Quercetin plasma concentration arm 3 vs. arm 4
timeFrame: 24 hours
measure: Quercetin plasma concentration arm 3 vs. arm 4
timeFrame: 24 hours
measure: Quercetin plasma concentration arm 3 vs. arm 4
timeFrame: 24 hours
measure: Quercetin plasma concentration arm 3 vs. arm 4
timeFrame: 24 hours
measure: Quercetin plasma concentration arm 3 vs. arm 4
timeFrame: 24 hours
Other outcomes:
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Study officials:
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