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

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

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Covid19; SARS-CoV Infection
• Intervention / Treatment: Drug: Fisetin; Drug: Placebo

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 Type: Interventional
• Enrollment (Actual): 20
• Phase: Phase 2

Contacts and Locations

Study Locations

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

Participation Criteria

Eligibility Criteria

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

Description

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.
18. History of diverticulitis or diverticulosis with GI bleeding, as per clinical judgment.

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
Placebo Comparator: Placebo Group; Subjects will receive placebo	Drug: Placebo; Placebo looks exactly like the treatment drug, but it contains no active ingredient
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 Names: 3,3',4',7-tetrahydroxyflavone

What is the study measuring?

Primary Outcome Measures

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

Collaborators and Investigators

• Sponsor: Mayo Clinic
• Collaborators: National Institute on Aging (NIA)
• Investigators: Principal Investigator: James L Kirkland, MD, PhD, Mayo Clinic

Publications and helpful links

Helpful Links

• Mayo Clinic Clinical Trials

Study record dates

Study Major Dates

• Study Start (Actual): April 29, 2022
• Primary Completion (Estimated): August 31, 2024
• Study Completion (Estimated): November 30, 2024

Study Registration Dates

• First Submitted: September 1, 2020
• First Submitted That Met QC Criteria: September 1, 2020
• First Posted (Actual): September 3, 2020

Study Record Updates

• Last Update Posted (Actual): April 11, 2024
• Last Update Submitted That Met QC Criteria: April 9, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia, Viral; Pneumonia; Lung Diseases; Severe Acute Respiratory Syndrome; COVID-19
• Other Study ID Numbers: 20-008867; 1R01AG072301-01 (U.S. NIH Grant/Contract)

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