COVID-FIS: Pilot in COVID-19 (SARS-CoV-2) of Fisetin in Older Adults in Nursing Homes (COVID-FIS)

• ClinicalTrials.gov Identifier: NCT04537299
• Recruitment Status: Enrolling by invitation
• First Posted: September 3, 2020
• Last Update Posted: March 8, 2022
• Sponsor: Mayo Clinic
• Collaborator: National Institute on Aging (NIA)
• Information provided by (Responsible Party): James L. Kirkland, MD, PhD, Mayo Clinic

Study Description

Brief Summary:

The purpose of this study is to test whether Fisetin, a senolytic drug, can assist in preventing an increase in the disease's progression and alleviate complications of coronavirus due to an excessive inflammatory reaction.

Condition or disease	Intervention/treatment	Phase
Covid19; SARS-CoV Infection	Drug: Fisetin; Drug: Placebo	Phase 2

Detailed Description:

This study is a pilot, randomized, placebo-controlled, single-center study of Fisetin in elderly nursing home participants with non-, mildly-, or moderately-symptomatic and confirmed SARS-CoV-2 infection.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 150 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: COVID-FIS: A Phase 2 Placebo-Controlled Pilot Study in COVID-19 of Fisetin to Alleviate Dysfunction and Excessive Inflammatory Response in Older Adults in Nursing Homes
• Actual Study Start Date: January 25, 2022
• Estimated Primary Completion Date: December 2023
• Estimated Study Completion Date: December 2023

Arms and Interventions

Arm	Intervention/treatment
Experimental: Treatment Group; Subjects will receive treatment drug (Fisetin)	Drug: Fisetin; ~20 mg/kg/day oral, NG or D tube course for 2 consecutive days twice (Days 0 & 1 and Days 8 & 9); Other Name: 3,3',4',7-tetrahydroxyflavone
Placebo Comparator: Placebo Group; Subjects will receive placebo	Drug: Placebo; Placebo looks exactly like the treatment drug, but it contains no active ingredient

Outcome Measures

Primary Outcome Measures :

1. Change in COVID-19 Severity [ Time Frame: baseline, Day 2, 7, 10, 14, 17, 30, 90 and 180 ]
   Ordinal Scale for Clinical Improvement (minimum=0 and maximum=8; higher score = worse outcome)

Eligibility Criteria

• Ages Eligible for Study: 65 Years and older (Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

1. Men or post-menopausal women age ≥65 years.
2. Current nursing home resident.
3. CoV severity of moderate or less OR SpO2 ≥ 85% (on room air or ≤ 2 L of supplemental oxygen at time of enrollment.
4. SARS-CoV-2 infection confirmed by PCR test at Mayo Clinic or other CLIA certified laboratory within 10 days before randomization.
5. Willing and able to provide written informed consent or have a legally authorized representative (LAR) who will provide informed consent.

Exclusion Criteria:

1. Presence of any condition that the Investigator or the subject's attending physician, physician's assistant, or nurse-practitioner believes would put the subject at risk or would preclude the patient from successfully completing the trial.
2. Pregnancy (note that only post-menopausal women will be enrolled).
3. Total bilirubin >3X upper limit of normal or as per clinical judgment.
4. Serum aspartate transaminase (AST) or alanine aminotransferase (ALT) >4x the upper limits of normal or as per clinical judgment.
5. Hemoglobin <7 g/dL; white blood cell count ≤2,000/mm3 (≤2.0 x 109/L) or ≥25,000/mm3 (≥25 x 109/L); platelet count ≤ 40,000/μL (≤40 x 109/L); absolute neutrophil count ≤1 x 109/L; lymphocyte count <0.3 x 109/L at screening or as per clinical judgment.
6. Unstable (as per clinical judgment) major cardiovascular, renal, endocrine, immunological, or hepatic disorder.
7. eGFR <25 ml/ min/ 1.73 m2 or as per clinical judgment.
8. Plasma and/or serum glucose >300 or as per clinical judgment.
9. Human immunodeficiency virus infection.
10. Known active hepatitis B or C infection.
11. Invasive fungal infection.
12. Uncontrolled (as per clinical judgment) pleural/pericardial effusions or ascites.
13. New/active invasive cancer except non-melanoma skin cancers as per clinical judgment.
14. Known condition associated with major immunodeficiency as per clinical judgment.
15. Known hypersensitivity or allergy to Fisetin.

16. Subjects taking any of the medications listed in Protocol Appendix 1 may participate if they are otherwise eligible AND the medication can be safely held during the following times:

    • Immediately before the 1st IP administration (Day 0) until at least 10 hours after the 2nd IP administration (Day 1)
    • Immediately before the 3rd IP administration (Day 8) until at least 10 hours after the 4th IP administration (Day 9)
17. Participation in other clinical trials involving treatment for COVID-19. Note that institutional standard of care treatment of COVID-19 including glucocorticoids, hydroxychloroquine, azithromycin, remdesivir, anti-spike antibodies, and/or convalescent plasma are not excluded from the study.

Contacts and Locations

Locations

United States, Minnesota

Mayo Clinic

Rochester, Minnesota, United States, 55905

Sponsors and Collaborators

Mayo Clinic

National Institute on Aging (NIA)

Investigators

• Principal Investigator: James L Kirkland, MD, PhD; Mayo Clinic

More Information

Additional Information:

Mayo Clinic Clinical Trials 

• Responsible Party: James L. Kirkland, MD, PhD, Principal Investigator, Mayo Clinic
• ClinicalTrials.gov Identifier: NCT04537299
• Other Study ID Numbers: 20-008867; 1R01AG072301-01 ( U.S. NIH Grant/Contract )
• First Posted: September 3, 2020
• Last Update Posted: March 8, 2022
• Last Verified: March 2022

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• 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

Additional relevant MeSH terms:

COVID-19; Severe Acute Respiratory Syndrome; Respiratory Tract Infections; Infections; Pneumonia, Viral; Pneumonia; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases