Mushroom-based Product for COVID-19

Study Overview
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Brief Summary
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This is a multi-center, randomized, double-blind, placebo-controlled clinical trial to evaluate two polypore mushrooms, Fomitopsis officinalis and Trametes versicolor (FoTv), to treat COVID-19-positive outpatients with mild-to-moderate symptoms assigned to self-quarantined and home management. The study aims to establish the safety and feasibility of the use of FoTv vs placebo in 66 total subjects.

Detailed Description
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Despite biomedical advances, medical intervention for COVID-19 is largely limited to vaccinations and supportive care during the later stages of disease. While antiviral, anti-inflammatory, and antimalarial options have been explored for later stages of disease, fewer studies have been conducted on medications to reduce the risk of outpatient cases progressing to severe disease. Therefore, it is important that we broaden the search to include agents outside of our usual pharmacopeia. Integrative Medicine offers several promising therapeutics that are available today and warrant investigation. Some of the botanicals used for their possible immune modulating functions include polypore mushrooms. Among these, Turkey Tail (Trametes versicolor) has a long history of use for its immune supporting properties. An RCT examining the effects of Trametes versicolor in breast cancer patients detected increases in lymphocyte counts and natural killer cell functional activity (Torkelson et al, 2012 and Benson et al, 2019) both of which are key to host COVID-19 response. Further investigations into other relevant mushroom species demonstrated that Agarikon (Fomitopsis officinalis) can strongly induce an array of differential cytokine responses associated with both immune-activation and resolution of host defense- induced inflammatory reactions (unpublished). This homeostatic effect deserves attention for COVID-19 given the high mortality rate associated with cytokine storm. This is a multi-center, randomized, double blind, placebo-controlled clinical trial to evaluate two polypore mushrooms, Fomitopsis officinalis and Trametes versicolor (FoTv), to treat COVID-19-positive outpatients with mild-to-moderate symptoms assigned to self-quarantined and home management. This study aims to establish the safety and feasibility of the use of FoTv vs placebo in 66 total subjects. Subsequent trials will evaluate Chinese herbal medicine as well as the efficacy of FoTv in a larger study population.

Official Title
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Multicenter Double Blind, Placebo Controlled RCT of Fomitopsis Officinalis and Trametes Versicolor to Treat COVID-19

Conditions
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COVID-19

Intervention / Treatment
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* Drug: FoTv


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Positive COVID-19 diagnosis within the prior 72 hours Age 18 years and older Women of childbearing potential must have a negative urine or serum hCG. Women of childbearing potential must have a negative serum pregnancy test at screening and agree to use contraception throughout the study period. Capable of documenting vitals, symptoms, and study product intake daily and communicating this information to the study team Willing to avoid alcohol, cannabis, and dairy products during the study period. Exclusion Criteria: Any of the following symptoms which, according to the CDC, require hospitalization: Trouble breathing Persistent pain or pressure in the chest New confusion or inability to arouse Bluish lips or face Current use of investigational agents to prevent or treat COVID-19 Known liver disease (ALT/AST >3x ULN or diagnosis of cirrhosis) Known renal disease (eGFR < 60 ml/min) or acute nephritis. Uncontrolled hypertension (SBP>140 or DBP>90 while on medications) Pregnant or breastfeeding women

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Mushrooms<br>Fomitopsis officinalis and Trametes versicolor | Drug: FoTv<br>* 8 capsules three times a day for 14 consecutive days.<br>* Other names: Fomitopsis officinalis and Trametes versicolor;|
| Placebo Comparator: Placebo<br>Organic brown rice | Drug: FoTv<br>* 8 capsules three times a day for 14 consecutive days.<br>* Other names: Fomitopsis officinalis and Trametes versicolor;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adverse Events | The safety of the study medication will be assessed by number and severity of participants with treatment-related adverse events as assessed by Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events Corrected Version 2.1 July 2017 between the two study arms. | 2 months | 
| Creatinine | The safety of the study medication will also assessed by a comparison of the serum creatinine level of baseline laboratory data with end-of-treatment labs or on hospital admission labs (for hospitalized patients) | 2 months | 
| Aspartate transaminase | The safety of the study medication will also assessed by a comparison of the aspartate transaminase of baseline laboratory data with end-of-treatment labs or on hospital admission labs (for hospitalized patients) | 2 months | 
| Alanine transaminase | The safety of the study medication will also assessed by a comparison of the alanine transaminase of baseline laboratory data with end-of-treatment labs or on hospital admission labs (for hospitalized patients) | 2 months | 
| Prothrombin time | The safety of the study medication will also assessed by a comparison of the prothrombin time of baseline laboratory data with end-of-treatment labs or on hospital admission labs (for hospitalized patients) | 2 months | 
| Partial Thromboplastin Time | The safety of the study medication will also assessed by a comparison of the Partial Thromboplastin Time of baseline laboratory data with end-of-treatment labs or on hospital admission labs (for hospitalized patients) | 2 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Duration of viral illness | A secondary exploratory objective will be to evaluate COVID-19 severity among subjects in each of the two medication arms, compared with placebo, as ascertained by duration of COVID-19 acute viral illness (as measured by fever and self-reported symptom scores) | 6 months | 
| Hospitalization rate | A secondary exploratory objective will be to evaluate COVID-19 severity among subjects in each of the two medication arms, compared with placebo, as ascertained by hospitalization rate. | 6 months | 
| ICU admission | A secondary exploratory objective will be to evaluate COVID-19 severity among subjects in each of the two medication arms, compared with placebo, as ascertained by ICU admission rate. | 6 months | 
| Ventilatory requirement | A secondary exploratory objective will be to evaluate COVID-19 severity among subjects in each of the two medication arms, compared with placebo, as ascertained by maximum ventilatory requirement during hospitalization, if applicable. | 6 months | 
| Lymphocyte count | A secondary exploratory objective will be to evaluate COVID-19 severity among subjects in each of the two medication arms, compared with placebo, as ascertained by comparing the lymphocyte count of baseline laboratory data with end-of-treatment labs or on hospital admission labs (for hospitalized patients). | 6 months | 
| Neutrophil count | A secondary exploratory objective will be to evaluate COVID-19 severity among subjects in each of the two medication arms, compared with placebo, as ascertained by comparing the neutrophil count of baseline laboratory data with end-of-treatment labs or on hospital admission labs (for hospitalized patients). | 6 months | 
| Ferritin | A secondary exploratory objective will be to evaluate COVID-19 severity among subjects in each of the two medication arms, compared with placebo, as ascertained by comparing the serum ferritin level of baseline laboratory data with end-of-treatment labs or on hospital admission labs (for hospitalized patients). | 6 months | 
| D-Dimer | A secondary exploratory objective will be to evaluate COVID-19 severity among subjects in each of the two medication arms, compared with placebo, as ascertained by comparing the serum d-dimer level of baseline laboratory data with end-of-treatment labs or on hospital admission labs (for hospitalized patients). | 6 months | 
| Lactate Dehydrogenase | A secondary exploratory objective will be to evaluate COVID-19 severity among subjects in each of the two medication arms, compared with placebo, as ascertained by comparing the serum Lactate Dehydrogenase level of baseline laboratory data with end-of-treatment labs or on hospital admission labs (for hospitalized patients). | 6 months | 
| C-Reactive Protein | A secondary exploratory objective will be to evaluate COVID-19 severity among subjects in each of the two medication arms, compared with placebo, as ascertained by comparing the serum C-Reactive Protein level of baseline laboratory data with end-of-treatment labs or on hospital admission labs (for hospitalized patients). | 6 months | 
| Troponin | A secondary exploratory objective will be to evaluate COVID-19 severity among subjects in each of the two medication arms, compared with placebo, as ascertained by comparing the serum troponin level of baseline laboratory data with end-of-treatment labs or on hospital admission labs (for hospitalized patients). | 6 months | 
| Mid-turbinate nasal swabs | A secondary exploratory objective will be to evaluate COVID-19 severity among subjects in each of the two medication arms, compared with placebo, as ascertained by changes in the SARS CoV-2 viral loads among mid-turbinate nasal swabs taken on days 0, 4, 7 and 14. | 6 months | 
| Peripheral Blood Mononuclear Cell (PBMC) immune profiling | A secondary exploratory objective will be to evaluate immune response to FoTv in the setting of COVID-19 infection by comparing the PBMC transcriptome between subjects in each of the two arms. | 6 months |