COVID-19, Cytokine Storm
Conditions
Keywords
IL-6, fluoxetine, cytokine storm, NF-KB, COVID-19
Brief summary
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.
Interventions
DRUGFluoxetine
Fluoxetine 20 mg to 60 mg daily given from 2 weeks to 2 months duration
Sponsors
University of Toledo Health Science Campus
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
All patients who enter the study will be monitored daily for symptoms of COVID-19. Patients may choose to take fluoxetine or to have treatment as usual. Patients may also choose to have blood drawn and stored for a future analysis of cytokines.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Outpatient Subject Hospitalizations | 2 months | whether the subject is hospitalized for COVID-19 symptoms |
| Number of Subjects Undergoing Intubation | 2 months | whether the subject is intubated for COVID-19 symptoms |
| Number of Patients Who Died Within 2 Months of Entry Into the Study | 2 months | Patients who died from any cause within 2 months of entry into the study. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Participants With 1 or More Symptom Free Day With no COVID Primary Symptoms During 2 Months After Study Entry | 2 months | 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 |
| Participants With Patient Health Questionnaire (PHQ) -9 Score Below 10 After Baseline Assessment | 2 months | 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 |
| Participants With Generalized Anxiety Disorder (GAD) -7 Scale Score Below 10 After Baseline Assessment | 2 months | 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 |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Treatment As Usual Participants may choose to not take fluoxetine and remain in the study | 4 |
| 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
Fluoxetine: Fluoxetine 20 mg to 60 mg daily given from 2 weeks to 2 months duration | 11 |
| Total | 15 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Withdrawal by Subject | 0 | 1 |
Baseline characteristics
| Characteristic | Treatment As Usual | Fluoxetine | Total |
|---|---|---|---|
| Age, Continuous | 52 Years | 46.09 Years | 47.67 Years |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 4 Participants | 10 Participants | 14 Participants |
| Region of Enrollment United States | 4 participants | 11 participants | 15 participants |
| Sex: Female, Male Female | 3 Participants | 7 Participants | 10 Participants |
| Sex: Female, Male Male | 1 Participants | 4 Participants | 5 Participants |
| Smoke Cigarettes Does not smoke cigarettes | 3 Participants | 10 Participants | 13 Participants |
| Smoke Cigarettes Smokes cigarettes | 1 Participants | 1 Participants | 2 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 1 / 4 | 0 / 11 |
| other Total, other adverse events | 0 / 4 | 0 / 11 |
| serious Total, serious adverse events | 1 / 4 | 0 / 11 |
Outcome results
Primary
Number of Outpatient Subject Hospitalizations
whether the subject is hospitalized for COVID-19 symptoms
Time frame: 2 months
Population: We had intended this measure for outpatients but had very few study participants who were outpatients.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Treatment As Usual | Number of Outpatient Subject Hospitalizations | 0 Participants |
| Fluoxetine | Number of Outpatient Subject Hospitalizations | 0 Participants |
Primary
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.
Time frame: 2 months
Population: review of charts to determine death by any cause within 2 months of entry into study
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Treatment As Usual | Number of Patients Who Died Within 2 Months of Entry Into the Study | 1 Participants |
| Fluoxetine | Number of Patients Who Died Within 2 Months of Entry Into the Study | 0 Participants |
Primary
Number of Subjects Undergoing Intubation
whether the subject is intubated for COVID-19 symptoms
Time frame: 2 months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Treatment As Usual | Number of Subjects Undergoing Intubation | 1 Participants |
| Fluoxetine | Number of Subjects Undergoing Intubation | 0 Participants |
Secondary
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
Time frame: 2 months
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Treatment As Usual | Participants With 1 or More Symptom Free Day With no COVID Primary Symptoms During 2 Months After Study Entry | 1 or more symptom free days | 3 Participants |
| Treatment As Usual | Participants With 1 or More Symptom Free Day With no COVID Primary Symptoms During 2 Months After Study Entry | no symptom free days | 1 Participants |
| Fluoxetine | Participants With 1 or More Symptom Free Day With no COVID Primary Symptoms During 2 Months After Study Entry | 1 or more symptom free days | 7 Participants |
| Fluoxetine | Participants With 1 or More Symptom Free Day With no COVID Primary Symptoms During 2 Months After Study Entry | no symptom free days | 4 Participants |
Secondary
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
Time frame: 2 months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Treatment As Usual | Participants With Generalized Anxiety Disorder (GAD) -7 Scale Score Below 10 After Baseline Assessment | 4 Participants |
| Fluoxetine | Participants With Generalized Anxiety Disorder (GAD) -7 Scale Score Below 10 After Baseline Assessment | 10 Participants |
Secondary
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
Time frame: 2 months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Treatment As Usual | Participants With Patient Health Questionnaire (PHQ) -9 Score Below 10 After Baseline Assessment | 4 Participants |
| Fluoxetine | Participants With Patient Health Questionnaire (PHQ) -9 Score Below 10 After Baseline Assessment | 10 Participants |