Fisetin for Immune Deficiency-Related Lung Disease

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Avni Joshi

Disqualifiers: Pregnancy, Tobacco use, Excessive caffeine, others

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 4 weeks

20 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial is testing whether a natural supplement called Fisetin can help people with common variable immunodeficiency (CVID). CVID patients often struggle with infections due to a weak immune system. Fisetin might help by reducing inflammation and strengthening their immune response.

Do I have to stop taking my current medications for the trial?

The trial information does not specify whether you need to stop taking your current medications. Please consult with the trial coordinators or your doctor for guidance.

What evidence supports the effectiveness of the drug fisetin for treating immune deficiency-related lung disease?

Research shows that fisetin, a natural compound found in fruits and vegetables, can reduce lung inflammation and improve lung function in conditions like acute lung injury and asthma by blocking certain pathways (NF-κB signaling) that cause inflammation. This suggests it might help with lung diseases related to immune deficiency by reducing inflammation and improving lung health. ^{1 2 3 4 5}

Is fisetin safe for human use?

Fisetin, a natural compound found in fruits and vegetables, has shown anti-inflammatory and antioxidant properties in animal studies without any reported adverse effects. In studies involving mice, fisetin and its derivatives did not show any toxicity, suggesting it may be generally safe, but human studies are needed to confirm this. ^{1 3 6 7 8}

How is the drug Fisetin unique in treating immune deficiency-related lung disease?

Fisetin is unique because it is a natural compound found in fruits and vegetables that has anti-inflammatory and antioxidant properties, and it works by inhibiting specific signaling pathways (like NF-κB) involved in inflammation, which may help reduce lung inflammation and improve lung function in immune deficiency-related lung disease. ^{1 3 4 9 10}

Research Team

Avni Joshi, MD

Principal Investigator

Mayo Clinic

Eligibility Criteria

This trial is for adults with Common Variable Immunodeficiency (CVID) and associated lung disease, who have been diagnosed according to international standards. Participants must not be pregnant or at risk of pregnancy without contraception, should not use tobacco or consume excessive caffeine, and must be capable of following the study's procedures.

Inclusion Criteria

IgA levels are abnormal.

Patient must be able and willing to comply with the requirements of this study protocol

I am a woman who cannot become pregnant because I am postmenopausal or have been surgically sterilized.

Exclusion Criteria

People who are in prison, living in an institution, or who may have difficulty making their own decisions, such as those with dementia.

Pregnant and/or lactating. Women of childbearing potential (WCBP) must have a negative pregnancy test within 72 hours prior to randomization

I am currently in the hospital or might need to be hospitalized soon.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Fisetin or placebo for 2 cycles of 2 consecutive days each, on days 0 & 1 and repeated on days 28 & 29

4 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment, including changes in FVC, radiologic imaging, and quality of life

6 months

Treatment Details

Interventions

• Fisetin
• Placebo

Trial Overview The trial is testing Fisetin, a dietary supplement, against a placebo to see if it can treat interstitial lung disease in patients with CVID. The effectiveness of Fisetin will be compared to that of an inactive substance to determine its potential as a treatment option.

Participant Groups

Group I: Fisetin Group Experimental Treatment 1 Intervention

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)

Group II: Placebo Group Placebo Group 1 Intervention

Subjects will receive placebo for 2 cycles of 2 consecutive days (first on days 0 \& 1 and then repeated on days 28 \& 29)

Who Is Running the Clinical Trial?

Avni Joshi

Lead Sponsor

Trials

1

Recruited

20+

Findings from Research

In a mouse model of acute pulmonary inflammation, the flavonoid fisetin significantly reduced levels of inflammatory markers and mediators, outperforming other flavonoids and the glucocorticoid dexamethasone.

Fisetin's ability to lower myeloperoxidase levels and gene expression of inflammatory mediators suggests it could be a promising candidate for treating pulmonary inflammatory diseases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Inhibition of LPS-induced pulmonary inflammation by specific flavonoids. Geraets, L., Haegens, A., Brauers, K., et al.[2021]

References

1. United States pubmed.ncbi.nlm.nih.gov

Fisetin Alleviates Lipopolysaccharide-Induced Acute Lung Injury via TLR4-Mediated NF-κB Signaling Pathway in Rats. [2021]

2. Netherlands pubmed.ncbi.nlm.nih.gov

Fisetin, a bioactive flavonol, attenuates allergic airway inflammation through negative regulation of NF-κB. [2016]

3. United States pubmed.ncbi.nlm.nih.gov

Immunosuppressive effects of fisetin in ovalbumin-induced asthma through inhibition of NF-κB activity. [2021]

4. Netherlands pubmed.ncbi.nlm.nih.gov

Flavonols attenuate the immediate and late-phase asthmatic responses to aerosolized-ovalbumin exposure in the conscious guinea pig. [2013]

5. United States pubmed.ncbi.nlm.nih.gov

Fisetin Suppresses Pulmonary Inflammatory Responses Through Heme Oxygenase-1 Mediated Downregulation of Inducible Nitric Oxide Synthase. [2021]

6. United States pubmed.ncbi.nlm.nih.gov

Inhibition of LPS-induced pulmonary inflammation by specific flavonoids. [2021]

7. United States pubmed.ncbi.nlm.nih.gov

Effects of Fisetin on Allergic Contact Dermatitis via Regulating the Balance of Th17/Treg in Mice. [2023]

8. United States pubmed.ncbi.nlm.nih.gov

A novel 4'-brominated derivative of fisetin induces cell cycle arrest and apoptosis and inhibits EGFR/ERK1/2/STAT3 pathways in non-small-cell lung cancer without any adverse effects in mice. [2023]

9. England pubmed.ncbi.nlm.nih.gov

Fisetin inhibits TNF-α/NF-κB-induced IL-8 expression by targeting PKCδ in human airway epithelial cells. [2021]

10. Netherlands pubmed.ncbi.nlm.nih.gov

Fisetin attenuates cerulein-induced acute pancreatitis through down regulation of JNK and NF-κB signaling pathways. [2021]