Pilot Trial of Fisetin in Healthy Volunteers and Older Patients With Multimorbidity

NCT06431932 | Recruiting Phase 1 DMC

• 2 other identifiers: Fisetin HIGH2023-506284-34-00
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

Brief Summary

The accumulation of senescent cells with age is a central mechanism that contributes to the development of chronic diseases, primarily by driving systemic chronic inflammation. Senolytic compounds such as fisetin can selectively target senescent cells for elimination and reduce multiple age-related pathologies in animal models. We will conduct a clinical trial in healthy volunteers and older patients with multiple chronic diseases. The participants will receive fisetin or placebo for two days, after which they will be examined at regular intervals for up to three months. We will investigate how fisetin is absorbed and metabolized by the body, and whether fisetin is safe. We will also identify methods to best measure the effect of fisetin on chronic inflammation, senescent cells, and general health.

Conditions

Multimorbidity; Healthy

Keywords

Senolytic; Pharmacokinetics; Chronic inflammation

Outcome Measures

Primary Outcomes (3)

• Population-based pharmacokinetic model for fisetin and metabolites

  To develop a population-based pharmacokinetic (popPK) model for fisetin and its main metabolites in healthy volunteers and older patients, covariates such as body weight, body composition, age, and CYP inducers/inhibitors will be tested for influence on interindividual variability.

  24 hours

• Adverse events

  Number of participants to experience adverse events

  Day 1 to 3

• suPAR

  The change in plasma levels of suPAR and a sample size calculation based on these data.

  Day 1 to 29

Secondary Outcomes (15)

• Population-based PKPD model for fisetin

  24 hours

• Renal excretion of fisetin and its main metabolites

  24 hours

• Symptoms and adverse events

  Day 1 to 3

• SASP factors and inflammation markers

  Healthy volunteers: day 1, 2, 29. Older patients: day 1, 2, 8, 15, 29, 57, 84.

• Senescence

  Healthy volunteers: day 1, 29. Older patients: day 1, 8, 15, 29, 84.

Study Arms (3)

Single-arm open-label study in healthy volunteers

EXPERIMENTAL

Healthy volunteers will receive fisetin.

Drug: Fisetin

RCT - Treatment group

EXPERIMENTAL

Older patients with multimorbidity will receive fisetin.

Drug: Fisetin

RCT - Placebo group

PLACEBO COMPARATOR

Older patients with multimorbidity will receive placebo.

Drug: Placebo

Interventions

Fisetin DRUG

Subjects will receive fisetin corresponding to 20 mg/kg/day for two consecutive days.

RCT - Treatment group; Single-arm open-label study in healthy volunteers

Placebo DRUG

Subjects will receive a corresponding number of placebo capsules for two consecutive days.

RCT - Placebo group

Eligibility Criteria

• Age: 20 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Aged 20-35 years
• suPAR levels \<3.5 ng/mL (± 15% corresponding to assay variation)
• Able to cooperate cognitively
• Able to read and understand Danish
• Women of childbearing potential must use effective contraception

You may not qualify if:

• Body weight \>100 kg
• Inability to swallow pills
• Pregnant and/or lactating
• Known hypersensitivity or allergy to fisetin or excipients in the placebo capsules
• Presence of any condition that the investigator believes would put the subject at risk or would preclude the participant from successfully completing all aspects of the trial
• Presence of known chronic diagnosis
• Active acute illness
• Prescribed medication, except contraceptives
• Previous cancer diagnosis or treatment
• Use of senolytic and other "anti-aging" supplements
• Older patients with multimorbidity:
• At screening #1 during hospital admission:
• Acutely hospitalized medical patient
• Age ≥65 years
• suPAR \>5 ng/mL (± 15% corresponding to assay variation)

Sponsors & Collaborators

• Mayo Clinic: collaborator
• Ove Andersen: lead
• University of Southern Denmark: collaborator

Study Sites (1)

Department of Clinical Research, Copenhagen University Hospital Amager & Hvidovre

Hvidovre, 2650, Denmark

RECRUITING

MeSH Terms

Interventions

fisetin

Study Officials

• Juliette Tavenier

  Copenhagen University Hospital, Amager and Hvidovre

  STUDY CHAIR

• Line Jee Hartmann Rasmussen

  Copenhagen University Hospital, Amager and Hvidovre

  STUDY CHAIR

• Morten B Houlind

  Copenhagen University Hospital, Amager and Hvidovre

  STUDY CHAIR

• Ove Andersen

  Copenhagen University Hospital, Amager and Hvidovre

  PRINCIPAL INVESTIGATOR

• Jan O Nehlin

  Copenhagen University Hospital, Amager and Hvidovre

  STUDY CHAIR

Central Study Contacts

Juliette Tavenier

CONTACT

+4538620640; juliette.tavenier@regionh.dk

Line Jee Hartmann Rasmussen

CONTACT

+4538620640; line.jee.hartmann.rasmussen@regionh.dk

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Head of Research, Clinical Professor, Principal Investigator

Model Details: The trial consists of: * a single-arm open-label study, in which healthy volunteers (n=20) will receive fisetin corresponding to 20 mg/kg/day for two consecutive days. * a 2-arm triple-blind randomized placebo-controlled study, in which older patients with multimorbidity (n=40) will receive either: * 20 mg/kg/day fisetin for two consecutive days, or * placebo for two consecutive days.

Study Record Dates

• First Submitted: May 15, 2024
• First Posted: May 29, 2024
• Study Start: March 24, 2026
• Primary Completion (Estimated): December 31, 2028
• Study Completion (Estimated): June 1, 2034
• Last Updated: March 27, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

DK (1)