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COVID-FISETIN: Pilot in SARS-CoV-2 of Fisetin to Alleviate Dysfunction and Inflammation

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04476953
Recruitment Status : Enrolling by invitation
First Posted : July 20, 2020
Last Update Posted : February 18, 2021
Sponsor:
Information provided by (Responsible Party):
James L. Kirkland, Mayo Clinic

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 Drug: Placebo Drug: Fisetin Phase 2

Detailed Description:
To determine if Fisetin treatment can prevent deterioration of oxygenation status as measured by S/F ratio: SpO2/ FiO2, as well as prevent deterioration in physical function (frailty) and hyper-inflammation, other measures of oxygenation status (progression to supplemental oxygen requirement, assisted breathing/ ventilation), and progression from mild/ moderate to severe/ critical proven SARS-CoV-2 infection in hospitalized patients and to evaluate the safety and tolerability of Fisetin in this patient population.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 70 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Official Title: COVID-FISETIN: A Phase 2 Placebo-Controlled Pilot Study in SARS-CoV-2 of Fisetin to Alleviate Dysfunction and Excessive Inflammatory Response in Hospitalized Adults
Actual Study Start Date : August 3, 2020
Estimated Primary Completion Date : July 2021
Estimated Study Completion Date : July 2021

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
Other Name: 3,3',4',7-tetrahydroxyflavone

Placebo Comparator: Placebo Group
Subjects will receive placebo
Drug: Placebo
Placebo looks exactly like the study drug, but it contains no active ingredient.




Primary Outcome Measures :
  1. Serious Adverse Events [ Time Frame: 6 months ]
    Number of participants to experience serious adverse events and hypersensitivity reactions.

  2. Change in oxygenation status [ Time Frame: baseline, Day 3, 7, 10, 14, 17 and 30; Months 3 and 6 ]
    change in oxygenation levels as measured by S/F ratio (SPO2/FiO2)


Secondary Outcome Measures :
  1. CoV Severity Category [ Time Frame: 6 months ]
    Number of participants to progress to severe or critical classification CoV



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria - Patients must meet all of the following inclusion criteria to be enrolled in this study.

  1. Men or women 60 years of age or older

    OR

    Age 18 - 59 years WITH at least one of the following comorbidities:

    • BMI greater than or equal to 35
    • Diabetes
    • Asthma/ Chronic Obstructive Pulmonary Disease (COPD)
    • Previous Myocardial Infarction
    • Previous Stroke/ Cerebrovascular Accident (CVA)
    • Hypertension/ Atherosclerosis/ Peripheral Vascular Disease
    • Smoking and/or vaping
    • Other conditions associated with senescent cell accumulation (i.e. previous chemotherapy or radiation)
  2. SpO2 greater than or equal to 85% (on room air or less than or equal to 2 L of supplemental oxygen)
  3. Willing and able to provide written informed consent or have a legally authorized representative (LAR) who will provide informed consent
  4. SARS-CoV-2 infection confirmed by PCR test at Mayo Clinic (or other CLIA certified) laboratory within 10 days prior to randomization.

Exclusion Criteria - Patients who meet any of the following exclusion criteria are not to be enrolled in this study.

General Exclusion Criteria

  1. 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
  2. Pregnant and/or lactating. Women of childbearing potential (WCBP) must have a negative pregnancy test within 72 hours prior to randomization
  3. 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
  4. 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

    Laboratory Exclusion Criteria

  5. Total bilirubin >3X upper limit of normal or as per clinical judgment.
  6. Serum aspartate transaminase (AST) or alanine aminotransferase (ALT) >4x the upper limits of normal or as per clinical judgment.
  7. Hemoglobin <7 g/dL; white blood cell count ≤ 2,000/mm3 (< or = 2.0 x 109/L) or > or = 20,000/mm3 (> or = 20 x 109/L); platelet count < or = 40,000/µL (< or = 40 x 109/L); absolute neutrophil count < or = 1 x 109/L; lymphocyte count <0.3 x 109/L at screening or as per clinical judgment.
  8. Unstable (as per clinical judgment) major cardiovascular, renal, endocrine, immunological, or hepatic disorder.
  9. eGFR <25 ml/ min/ 1.73 m2 or as per clinical judgment.
  10. Plasma and/or serum glucose >300 or as per clinical judgment.

    Clinical History Exclusion Criteria

  11. Human immunodeficiency virus infection.
  12. Known active hepatitis B or C infection.
  13. Invasive fungal infection.
  14. Uncontrolled (as per clinical judgement) pleural/pericardial effusions or ascites.
  15. New/active invasive cancer except non-melanoma skin cancers.

    Medication Exclusion Criteria (See Appendices 1-3 for additional information)

  16. Known hypersensitivity or allergy to Fisetin.
  17. Patients currently using medications which utilize CYP450 2C9 for metabolism. These medications include: Fosphenytoin, Phenytoin, Warfarin, Glimepiride, Diclofenac, Bosentan, and Glyburide. Patients taking any of these medications may participate if the medications can be held immediately before the 1st IP administration until at least 10 hours after the last (2nd) IP administration and the patient is otherwise eligible.
  18. Patients currently using medications which utilize CYP2C9, CYP2C19, CYP1A2, OATP1B1. These medications include: Olanzapine, Clozapine, Theophylline, Tizanidine, Warfarin, Rameltoen, Tacrine, Duloxetine, Mexiletine, Riluzole, and Atomoxetine. Patients taking any of these medications may participate if the medications can be held immediately before the 1st IP administration until at least 10 hours after the last (2nd) IP administration and the patient is otherwise eligible.
  19. Patients currently using medications which are strong inhibitors of CYP3A4. These medications include: Atazanavir, Ceritinib, Clarithromycin, Darunavir, Idelalisib, Indinavir, Itraconazole, Ketoconazole, Lopinavir, Mefipristone, Nefazodone, Nelfinavir, Ombitasivir-paritaprevir-ritonivir, Ombitasivir-paritaprevir-ritonivir-plus dasabuvir, Posaconazole, Saquinavir, Telithromycin, Tucatinib, and Voriconazole. Patients taking any of these medications may participate if the medications can be held immediately before the 1st IP administration until at least 10 hours after the last (2nd) IP administration and the patient is otherwise eligible.
  20. Patients currently using antifungals. If antifungals are absolutely necessary from an infectious disease perspective, then they will be allowed only if the levels are subtherapeutic or therapeutic.
  21. Patients taking any of these medications may participate if the medications can be held immediately before the 1st IP administration until at least 10 hours after the last (2nd) IP administration and the patient is otherwise eligible:

    • Cardiac: digoxin, flecainide, amiodarone
    • Psychiatric: lithium, thioridazine
    • Neurologic: carbamazepine, phenobarbital
    • Antimicrobial/fungal: aminoglycosides (e.g. amikacin, gentamicin, kanamycin, neomycin, netilmicin, paromomysin, streptomycin, tobramycin), rifampin
    • Anticoagulants/ Antiplatelets: warfarin
    • Others: methotrexate, nitroglycerin, St. John's wort, tyrosine kinase inhibitors, tacrine, diclofenac
  22. Participation in other clinical trials involving treatment for SARS-CoV-2. (unless reviewed and approved by the Principal Investigator). Note that institutional standard of care treatment of SARS-CoV-2 including glucocorticoids, hydroxychloroquine, azithromycin, remdesivir, anti-spike antibodies, and/or convalescent plasma are not excluded from the study.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04476953


Locations
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United States, Minnesota
Mayo Clinic in Rochester
Rochester, Minnesota, United States, 55905
Sponsors and Collaborators
Mayo Clinic
Investigators
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Principal Investigator: James L Kirkland Mayo Clinic
Additional Information:
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Responsible Party: James L. Kirkland, Principal Investigator, Mayo Clinic
ClinicalTrials.gov Identifier: NCT04476953    
Other Study ID Numbers: 20-003936
First Posted: July 20, 2020    Key Record Dates
Last Update Posted: February 18, 2021
Last Verified: February 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by James L. Kirkland, Mayo Clinic:
SARS-CoV-2