Ongoing Lung Decline With Age Intensified Response

NCT07676435 | Recruiting Phase 2 FDA Drug

• 1 other identifier: STUDY00003866
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

This Phase II, randomized, double-blind, placebo-controlled pilot study will evaluate the effects of fisetin, a senolytic flavonoid compound, on lung function and biomarkers of cellular senescence in older adults aged 60 years and older. Participants will include individuals with a history of at least 10 pack-years of smoking as well as age-matched never-smokers. Forty participants will be randomized to receive either fisetin or placebo using a short-course "hit-and-run" dosing strategy (approximately 20 mg/kg/day orally for 2 consecutive days on Days 1-2 and Days 8-9).

Conditions

Age-Related Lung Function Decline

Keywords

Aging; Cellular Senescence; Healthy Aging; Smoking-Related Lung Function Decline; Pulmonary Function; Smoking

Outcome Measures

Primary Outcomes (3)

• Forced Vital Capacity (FVC)

  Forced vital capacity measured by spirometry to assess lung function following treatment with fisetin versus placebo.

  Baseline and Day 14

• Forced Expiratory Volume in 1 Second (FEV1)

  Forced expiratory volume in one second measured by spirometry following treatment with fisetin versus placebo.

  Baseline and Day 14

• FEV1/FVC Ratio

  Ratio of FEV1 to FVC measured by spirometry following treatment with fisetin versus placebo.

  Baseline and Day 14

Secondary Outcomes (3)

• 6-Minute Walk Distance (6MWD)

  Baseline and Day 14

• Peak Oxygen Uptake (VO₂)

  Baseline and Day 14

• Biomarkers of Cellular Senescence

  Baseline and Day 14

Study Arms (2)

Fisetin

EXPERIMENTAL

Participants receive oral fisetin at approximately 20 mg/kg/day for 2 consecutive days on Days 1-2 and again on Days 8-9 using a senolytic "hit-and-run" dosing strategy.

Drug: Fisetin

Placebo

PLACEBO COMPARATOR

Participants receive matching placebo capsules administered on the same schedule as the fisetin arm (Days 1-2 and Days 8-9).

Drug: Placebo

Interventions

Fisetin DRUG

Participants randomized to the experimental arm will receive oral fisetin capsules administered at a target dose of approximately 20 mg/kg/day for 2 consecutive days on Days 1-2 and again on Days 8-9. Fisetin will be supplied as 100 mg capsules and dosed according to body weight using a senolytic "hit-and-run" treatment approach.

Fisetin

Placebo DRUG

Participants randomized to the control arm will receive matching placebo capsules administered orally on the same schedule as the fisetin arm (Days 1-2 and Days 8-9). Placebo will be used to maintain blinding and permit comparison of efficacy and safety outcomes between treatment groups.

Placebo

Eligibility Criteria

• Age: 60 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Adults aged 60 years and older who are physically capable of participating in study procedures;
• Willing to be randomized to fisetin or placebo; weight stable within the previous 2 months (\<5-pound change);
• No blood donation within 2 months before screening; absence of unstable chronic disease;
• Willing to maintain baseline activity level throughout the study;
• Body mass index \<30 kg/m²;
• Either a history of at least 10 pack-years of cigarette smoking or never-smoking status.

You may not qualify if:

• Electrocardiogram (ECG) abnormalities, including prolonged QTc.
• Use of fisetin, other flavonoid supplements, or known senolytic compounds within 6 months prior to screening.
• Resting systolic blood pressure \>160 mmHg or diastolic blood pressure \>110 mmHg.
• Known allergy or hypersensitivity to fisetin or any component of the study product.
• Active malignancy, except non-melanoma skin cancer.
• Clinically significant hepatic, renal, cardiovascular, endocrine, immunologic, metabolic, or other uncontrolled medical conditions that, in the opinion of the investigator, would interfere with study participation or interpretation of results.
• Clinically significant laboratory abnormalities, including severe anemia, leukopenia, thrombocytopenia, uncontrolled diabetes, advanced kidney disease, significant liver dysfunction, or evidence of systemic inflammation.
• Human immunodeficiency virus (HIV) infection, active hepatitis B or hepatitis C infection, or invasive fungal infection.
• History of diverticulitis or diverticulosis with gastrointestinal bleeding.
• Current use of systemic corticosteroids.
• Current use of warfarin.
• Current use of medications with significant interaction potential with fisetin, including selected CYP450 or transporter substrates, inhibitors, or inducers, unless such medications can be safely withheld according to protocol requirements.
• Recent medication, supplement, or lifestyle changes that may affect study outcomes, in the opinion of the investigator.
• Inability to perform required study procedures, including pulmonary function testing, exercise testing, or other protocol assessments.
• Unwillingness or inability to provide informed consent.

Sponsors & Collaborators

• Cedars-Sinai Medical Center: lead

Study Sites (1)

Cedars-Sinai Medical Center

Los Angeles, California, 90048, United States

RECRUITING

MeSH Terms

Conditions

Smoking

Interventions

fisetin

Condition Hierarchy (Ancestors)

Behavior

Central Study Contacts

Samuel Cohen, MD

CONTACT

310-423-1725; samuel.cohen@csmc.edu

Yunhee Choi-Kuaea

CONTACT

Yunhee.Choi-Kuaea@cshs.org

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: This is a quadruple-masked (participant, care provider, investigator, outcomes assessor) study. Participants will be randomized to receive either fisetin or placebo. The investigational product and placebo will be prepared and dispensed by the Research Pharmacy according to a predetermined randomization schedule. Participants, investigators, study staff involved in participant assessments, and outcome assessors will remain blinded to treatment assignment throughout the study. Only designated unblinded pharmacy personnel responsible for investigational product preparation and dispensing will have access to treatment allocation information. Blinding will be maintained until completion of study procedures unless unblinding is required for participant safety.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor of Medicine

Study Record Dates

• First Submitted: June 24, 2026
• First Posted: June 30, 2026
• Study Start: June 17, 2026
• Primary Completion (Estimated): June 16, 2027
• Study Completion (Estimated): July 15, 2027
• Last Updated: July 1, 2026

Record last verified: 2026-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)