Senolytics Treatment of Interstitial Lung Disease in Common Variable Immunodeficiency

Senolytics as a Novel Treatment for Interstitial Lung Disease in Common Variable Immunodeficiency (CVID)

The purpose of this study is to determine if the supplement, Fisetin, can be used as a treatment option for common variable immunodeficiency (CVID) by comparing its efficacy to placebo.

Study Overview

• Status: Active, not recruiting
• Conditions: Common Variable Immunodeficiency; Interstitial Lung Disease Due to Systemic Disease
• Intervention / Treatment: Drug: Fisetin; Drug: Placebo

• Study Type: Interventional
• Enrollment (Estimated): 20
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic in Rochester

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Patient must have received a diagnosis of CVID according to the international consensus document (ICON) at least 30 days before enrollment.
• Physician diagnosis of possible GLILD associated with CVID.
• IgA results.
• Female patient is either not of childbearing potential, defined as postmenopausal for at least 1 year or surgically sterile. (A negative pregnancy test for women whose menopausal status is determined by self-reported absence of menstrual periods in the past 12 months will be required within 72 hours prior to randomization).
• Patient must be able and willing to comply with the requirements of this study protocol.

Exclusion Criteria:

• Unable or unwilling to give informed consent.
• Presence of any condition that the Investigator or the subject's attending physician believes would put the subject at risk or would preclude the patient from successfully completing the trial.
• Pregnant and/or lactating. Women of childbearing potential (WCBP) must have a negative pregnancy test within 72 hours prior to randomization.

WCBP who are unwilling to abstain from sex or use an adequate method of contraception from the time of the first IP administration through 48 hours after the last IP administration.

• Men who are unwilling to abstain from sex with WCBP or use an adequate method of contraception from the time of the first IP administration through 48 hours after the last IP administration.
• Prisoners, institutionalized individuals, or others who may be considered vulnerable populations, such as individuals with dementia.
• Patient currently hospitalized or under immediate consideration for hospitalization.
• Current use of tobacco products or as per clinical judgement.
• Current excessive caffeine intake (400 mg or more per day).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Fisetin Group; Subjects will receive the supplement, Fisetin, for 2 cycles of 2 consecutive days (first on days 0 & 1 and then repeated on days 28 & 29)	Drug: Fisetin; 20 mg per kilogram (kg) of body weight supplied in 100 mg capsules and administered orally on days 0, 1, 28, and 29
Placebo Comparator: Placebo Group; Subjects will receive placebo for 2 cycles of 2 consecutive days (first on days 0 & 1 and then repeated on days 28 & 29)	Drug: Placebo; Looks exactly like the study drug, but it contains no active ingredient. Administered orally on days 0, 1, 28 and 29

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in immunophenotyping of peripheral T lymphocytes	Measured by percentage of activated CD4+25+ T cells	Baseline, 6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Forced Vital Capacity (FVC)	Measured by spirometry to determine the maximal amount of air that can be forcibly exhaled from the lungs after a full inhale, reported as liters (L)	Baseline, 6 months
Change in radiologic imaging in subjects	Number of subjects to have a 10% improvement with the CT scoring system. Radiologist will score the CT scans at each time point and changes in score at each time point will be noted.	Baseline, 3 months, 6 months
Use of MRI imaging for assessment of GLILD	Number of MRI images that were used to assess for GLILD compared to High-resolution Computed Tomography (HRCT) use	6 months
Infectious complications	Number of subjects to experience infectious complications	6 months
Adverse Events	Number of adverse events reported	6 months
Change in quality of life	Measured using the RAND 36-Short Form Survey Instrument (SF-36). The SF-36 Health Survey is a 36-item, participant-reported survey that measures patient health and disability. Possible scores range from 0 to 100, with 0 indicating maximum disability, and 100 indicating no disability	Baseline, 6 months
Change in 6 minute walk test	Number of subjects to have a 10% improvement in 6 minute walk test. The 6 minute walk test measures the distance a person is able to walk in 6 minutes.	Baseline, 6 months

Collaborators and Investigators

• Sponsor: Avni Joshi
• Investigators: Principal Investigator: Avni Joshi, MD, MS, Mayo Clinic

Publications and helpful links

Helpful Links

• Mayo Clinic Clinical Trials

Study record dates

Study Major Dates

• Study Start (Actual): April 12, 2023
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): December 1, 2026

Study Registration Dates

• First Submitted: October 21, 2022
• First Submitted That Met QC Criteria: October 21, 2022
• First Posted (Actual): October 25, 2022

Study Record Updates

• Last Update Posted (Actual): June 30, 2026
• Last Update Submitted That Met QC Criteria: June 26, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immune System Diseases; Immunologic Deficiency Syndromes; Common Variable Immunodeficiency; fisetin
• Other Study ID Numbers: 21-003119

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No