Fluoxetine to Reduce Intubation and Death After COVID19 Infection

This project will test the efficacy of fluoxetine to prevent serious consequences of COVID-19 infection, especially death. Becoming sick with COVID-19 virus or any other serious respiratory condition is not fun. However, the dramatic effects of the COVID-19 pandemic on human society stem from its significant mortality, not the number of individuals who become sick. This project aims to prevent serious outcomes such as hospitalization, respiratory failure and death during the time it takes to develop vaccinations and other strategies to prevent COVID-19 infectionPoor outcomes with COVID-19 infection such as hospitalization, respiratory failure, organ failure and death are associated with a dysfunctional exaggerated immune response, called a cytokine storm, that is triggered by Interleukin-6 expression (IL-6) and seems to occur around day 5 to 7 of symptoms. Fluoxetine has extraordinarily strong evidence in its action as a blocker of IL-6 and cytokine storms in both animal models of infection and in human illness such as rheumatoid arthritis and others. This action of fluoxetine is an entirely separate pathway than the serotonergic pathway that allows fluoxetine to act as an antidepressant. This pathway has been demonstrated in cell culture, in animal models, in human illness and by novel bioinformatics analyses of protein transcripts to be relatively unique for fluoxetine and appears to be a novel pathway. This project aims to inhibit the increase in IL-6 expression and thereby prevent the cytokine storm that causes poor outcomes. Patients who have tested positive or are presumptively positive for COVID-19 will be entered into the study and given the option to start the medication fluoxetine, which is demonstrated to prevent IL-6 surges in infectious and inflammatory conditions. Participants will be monitored daily for COVID-19 symptoms and weekly for side effects and tolerance of fluoxetine. A subset of patients will have blood drawn weekly and stored to monitor IL-6 and other cytokine levels at a later date.

This project aims to reduce the serious outcomes of COVID-19 infection by preventing or inhibiting the cytokine storm associated with organ failure, respiratory failure and death.

Study Overview

• Status: Completed
• Conditions: COVID-19; Cytokine Storm
• Intervention / Treatment: Drug: Fluoxetine

• Study Type: Interventional
• Enrollment (Actual): 16
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Ohio
    • Toledo, Ohio, United States, 43614
      • University of Toledo

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Patients aged 18 and above, able to give informed consent or with legally authorized representative
• COVID-19 test positive or presumptive positive awaiting COVID testing or results by following criteria: fever, cough and shortness of breath or presumptive positive by one of these 3 criteria (fever, cough or shortness of breath) and known exposure to COVID-19 positive individual in past 2 weeks

Overall Study Exclusion Criteria :

• Unable to give informed consent and no legal representativ
• Prisoner/ institutionalized patient
• Under age 18

Exclusion from Fluoxetine Arm:

• Active bleeding requiring blood products
• Bipolar disorder not on mood stabilizing medication*
• Known allergy or hypersensitivity to fluoxetine
• Currently taking the following medications : MAO I, pimozide, thioridine
• Currently taking hydroxychloroquine
• Pregnant or breastfeeding
• For hospitalized patients : QTc greater than 500 ms
• *Hospitalized patient may be on hydroxychloroquine if QTc<500 and the primary attending approves

Exclusion from Blood Sample Provision:

• Pregnant
• Self-report of under 110 pounds

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: Treatment As Usual; Participants may choose to not take fluoxetine and remain in the study
Active Comparator: Fluoxetine; Participants will take fluoxetine 20 mg initially, increasing as tolerated to a maximum of 60 mg until symptoms abate, then will be tapered by 20 mg per week off the fluoxetine Participants will be on fluoxetine for 2 weeks to 2 months depending on symptom duration	Drug: Fluoxetine; Fluoxetine 20 mg to 60 mg daily given from 2 weeks to 2 months duration; Other Names: prozac

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Outpatient Subject Hospitalizations	whether the subject is hospitalized for COVID-19 symptoms	2 months
Number of Subjects Undergoing Intubation	whether the subject is intubated for COVID-19 symptoms	2 months
Number of Patients Who Died Within 2 Months of Entry Into the Study	Patients who died from any cause within 2 months of entry into the study.	2 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Participants With 1 or More Symptom Free Day With no COVID Primary Symptoms During 2 Months After Study Entry	Participant who achieved remission from covid with no active covid symptoms (cough, fever, shortness of breath, fatigue, muscle aches, and loss of taste and smell) from study entry	2 months
Participants With Patient Health Questionnaire (PHQ) -9 Score Below 10 After Baseline Assessment	depression score rating from 0 to 27 where higher scores indicate worse depression Scores of 10 or more meet criteria for diagnosis as a mild depressive episode	2 months
Participants With Generalized Anxiety Disorder (GAD) -7 Scale Score Below 10 After Baseline Assessment	anxiety scale with scores ranging from 0 to 21 where higher scores indicate more severe anxiety Scores of 10 or more generally indicate anxiety that might meet criteria for diagnosis as an anxiety disorder	2 months

Collaborators and Investigators

• Sponsor: University of Toledo Health Science Campus

Study record dates

Study Major Dates

• Study Start (Actual): May 1, 2020
• Primary Completion (Actual): April 30, 2021
• Study Completion (Actual): April 30, 2021

Study Registration Dates

• First Submitted: April 18, 2020
• First Submitted That Met QC Criteria: May 4, 2020
• First Posted (Actual): May 6, 2020

Study Record Updates

• Last Update Posted (Actual): June 7, 2024
• Last Update Submitted That Met QC Criteria: June 5, 2024
• Last Verified: June 1, 2024

More Information

Terms related to this study

• Keywords: COVID-19; IL-6; cytokine storm; fluoxetine; NF-KB
• Additional Relevant MeSH Terms: Pathologic Processes; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia, Viral; Pneumonia; Lung Diseases; Systemic Inflammatory Response Syndrome; Inflammation; Shock; COVID-19; Cytokine Release Syndrome; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Psychotropic Drugs; Neurotransmitter Uptake Inhibitors; Membrane Transport Modulators; Serotonin Agents; Antidepressive Agents; Cytochrome P-450 Enzyme Inhibitors; Antidepressive Agents, Second-Generation; Cytochrome P-450 CYP2D6 Inhibitors; Selective Serotonin Reuptake Inhibitors; Fluoxetine
• Other Study ID Numbers: FRIDA COVID19

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