RCT of Fomitopsis Officinalis and Trametes Versicolor to Treat COVID-19

Phase 1

Completed

Conditions: COVID-19

Interventions: Drug: FoTv

Registration Number: NCT04667247

Lead Sponsor: Gordon Saxe

Brief Summary: 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: 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responses associated with both immune-activation and resolution of host defense- induced inflammatory reactions (unpublished).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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 54

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:
1. Trouble breathing
2. Persistent pain or pressure in the chest
3. New confusion or inability to arouse
4. 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

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	FoTv	Organic brown rice
Mushrooms	FoTv	Fomitopsis officinalis and Trametes versicolor

Primary Outcome Measures

Name	Time	Method
Total Protein Normal to Abnormal Transition	14 days	We examined participants who were normal at Baseline (Day 1). The Normal to Abnormal proportion reflects the proportion of participants with normal values at Day 1 that became abnormal at Day 14 relative to all participants with normal values at baseline.
Albumin Normal to Abnormal Transition	14 days	We examined participants who were normal at Baseline (Day 1). The Normal to Abnormal proportion reflects the proportion of participants with normal values at Day 1 that became abnormal at Day 14 relative to all participants with normal values at baseline.
Alkaline Phosphatase Normal to Abnormal Transition	14 days	We examined participants who were normal at Baseline (Day 1). The Normal to Abnormal proportion reflects the proportion of participants with normal values at Day 1 that became abnormal at Day 14 relative to all participants with normal values at baseline.
AST Normal to Abnormal Transition	14 days	We examined participants who were normal at Baseline (Day 1). The Normal to Abnormal proportion reflects the proportion of participants with normal values at Day 1 that became abnormal at Day 14 relative to all participants with normal values at baseline.
ALT Normal to Abnormal Transition	14 days	We examined participants who were normal at Baseline (Day 1). The Normal to Abnormal proportion reflects the proportion of participants with normal values at Day 1 that became abnormal at Day 14 relative to all participants with normal values at baseline.
Bilirubin Normal to Abnormal Transition	14 days	We examined participants who were normal at Baseline (Day 1). The Normal to Abnormal proportion reflects the proportion of participants with normal values at Day 1 that became abnormal at Day 14 relative to all participants with normal values at baseline.
Adj. EGFR Normal to Abnormal Transition	14 days	We examined participants who were normal at Baseline (Day 1). The Normal to Abnormal proportion reflects the proportion of participants with normal values at Day 1 that became abnormal at Day 14 relative to all participants with normal values at baseline.
Prothrombin Time Normal to Abnormal Transition	14 days	We examined participants who were normal at Baseline (Day 1). The Normal to Abnormal proportion reflects the proportion of participants with normal values at Day 1 that became abnormal at Day 14 relative to all participants with normal values at baseline.
APTT Normal to Abnormal Transition	14 days	We examined participants who were normal at Baseline (Day 1). The Normal to Abnormal proportion reflects the proportion of participants with normal values at Day 1 that became abnormal at Day 14 relative to all participants with normal values at baseline.
ESR Normal to Abnormal Transition	14 days	We examined participants who were normal at Baseline (Day 1). The Normal to Abnormal proportion reflects the proportion of participants with normal values at Day 1 that became abnormal at Day 14 relative to all participants with normal values at baseline.
CRP Normal to Abnormal Transition	14 days	We examined participants who were normal at Baseline (Day 1). The Normal to Abnormal proportion reflects the proportion of participants with normal values at Day 1 that became abnormal at Day 14 relative to all participants with normal values at baseline.
LDH Normal to Abnormal Transition	14 days	We examined participants who were normal at Baseline (Day 1). The Normal to Abnormal proportion reflects the proportion of participants with normal values at Day 1 that became abnormal at Day 14 relative to all participants with normal values at baseline.

Secondary Outcome Measures

Name	Time	Method
Total Bilirubin	14 days	comparison of the Total Bilirubin of baseline laboratory data with end-of-treatment labs
Prothrombin Time	14 days	comparison of the prothrombin time of baseline laboratory data with end-of-treatment labs
Aspartate Aminotransferase (AST)	14 days	Comparison of the aspartate transaminase of baseline laboratory data with end-of-treatment labs
Alanine Transaminase (ALT)	14 days	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)
Albumin	14 days	comparing Albumin of baseline laboratory data with end-of-treatment labs
Alkaline Phosphatase	14 days	comparing the Alkaline Phosphatase of baseline laboratory data with end-of-treatment labs
Lactate Dehydrogenase	14 days	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).
C-Reactive Protein	14 days	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).
Mid-turbinate SARS CoV-2 Viral Load	14 days	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.
ESR	14 days	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 ESR of baseline laboratory data with end-of-treatment labs or on hospital admission labs (for hospitalized patients).
Symptom Count	14 days	Symptom severity was assessed via a daily questionnaire across Days 0-14, where participants rated their symptoms on a scale of 0 (none or absent) to 3 (severe). A composite measure was created for each day, based on the 12 symptoms most commonly associated with COVID-19 (fever, fatigue, muscle aches, shortness of breath, shortness of breath upon exertion, cough, sore throat, stuffy nose, runny nose, loss of taste, loss of smell, headache), and counting the total number of symptoms present. scores of 1 or more were considered to be present.
Symptom Severities	14 days	Symptom severity was assessed via a daily questionnaire across Days 0-14, where participants rated their symptoms on a scale of 0 (none or absent) to 3 (severe). A composite measure was created for each day, based on the 12 symptoms most commonly associated with COVID-19 (fever, fatigue, muscle aches, shortness of breath, shortness of breath upon exertion, cough, sore throat, stuffy nose, runny nose, loss of taste, loss of smell, headache), and summing the total symptom severities. Higher symptom severities indicates a worse outcome. The minimum and maximum were: 0 to 36, respectively.
Adj. EGFR	14 days	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 Adj. EGFR of baseline laboratory data with end-of-treatment labs or on hospital admission labs (for hospitalized patients).
APTT	14 days	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 APTT of baseline laboratory data with end-of-treatment labs or on hospital admission labs (for hospitalized patients).
INR	14 days	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 INR of baseline laboratory data with end-of-treatment labs or on hospital admission labs (for hospitalized patients). The INR is a result of a blood test that measures how long it takes for blood to clot, also known as the prothrombin time (PT). The INR is calculated by comparing the PT to the mean normal prothrombin time (MNPT).

Trial Locations

Locations (2): University of California, Los Angeles
🇺🇸
Los Angeles, California, United States
University of California, San Diego
🇺🇸
San Diego, California, United States
University of California, Los Angeles
🇺🇸Los Angeles, California, United States