Mushroom-based Product for COVID-19 (MACH19)

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

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.

Study Overview

• Status: Active, not recruiting
• Conditions: COVID-19
• Intervention / Treatment: Drug: FoTv

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responses associated with both immune-activation and resolution of host defense- induced inflammatory reactions (unpublished).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

• Study Type: Interventional
• Enrollment (Actual): 54
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • Los Angeles, California, United States, 90095
      • University of California, Los Angeles
    • San Diego, California, United States, 92093
      • University of California, San Diego

Participation Criteria

Eligibility Criteria

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

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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
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
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
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
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
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

Collaborators and Investigators

• Sponsor: Gordon Saxe
• Collaborators: University of California, Los Angeles; University of California, Irvine
• Investigators: Principal Investigator: Andrew Shubov, MD, University of California, Los Angeles

Study record dates

Study Major Dates

• Study Start (Actual): December 3, 2020
• Primary Completion (Actual): May 15, 2023
• Study Completion (Estimated): December 1, 2023

Study Registration Dates

• First Submitted: December 3, 2020
• First Submitted That Met QC Criteria: December 11, 2020
• First Posted (Actual): December 14, 2020

Study Record Updates

• Last Update Posted (Actual): August 8, 2023
• Last Update Submitted That Met QC Criteria: August 4, 2023
• Last Verified: August 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia, Viral; Pneumonia; Lung Diseases; COVID-19
• Other Study ID Numbers: 200633-1a

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No