The Impact of Fecal Microbiota Transplantation as an Immunomodulation on the Risk Reduction of COVID-19 Disease Progression With Escalating Cytokine Storm and Inflammatory Parameters

NCT04824222 | Unknown Phase 3

• 2 other identifiers: FeMToCOVID2020-003915-84
• Study Type: interventional
• Target: 366
• Locations: 0 countries
• Sites: N/A

Brief Summary

The gut microbiota provides an intestinal biological barrier against pathogens and has a pivotal role in the maintenance of intestinal homeostasis and modulation of the host immune system. The gut microbiota in a dysbiotic state has increasingly been implicated in the pathogenesis and progression of numerous diseases. However, whether dysbiosis reflects changes caused by the disease itself, or should be considered as a driving step in the pathogenesis, is not always understood. Dysbiosis results in the disturbance of several metabolic pathways that influence immunological and mechanical processes both in and outside the intestine, and it impairs colonization resistance. These processes may be reverted by fecal microbiota transplantation (FMT). FMT is a type of treatment that relies on transferring the microbiota that targets and corrects intestinal dysbiosis. FMT is based on collecting stool from healthy donors and - after preparation - administering the material to an individual with a specific disease. In summary, a subset of the symptoms associated with COVID-19 during the initial phase are intestinal complications, such as vomiting or diarrhea. Detecting these symptoms might not only lead to slowdown in transmission but also open the door to novel treatments that could reduce the severity of COVID-19.There is a positive correlation between severity of patient condition and level of proinflammatory cytokines (cytokine storm) in group of patients with COVID 19. Though numerous studies have been published on FMT for the treatment of certain diseases, there are only scarce studies on FMT for the treatment of SARS-CoV-2. Antiviral mechanism depended on the gut-lung axis was intimately proved in case of flu virus. The same dependency is observed in SARS CoV2 as well. That seems, good condition of intestinal microbiota could impact on antiviral effects and inhibits replication of virus. This leads to inhibit progress of inflammatory process in lung tissue. Silencing of inflammatory process through reestablish right influence of gut-lung axis could be fundamental meaning in arresting of cytokines storm and development of ARDS in patients with COVID-19. The scientist rationale definitely argue a clear need to studies of gut wellbeing in COVID 19 and using FMT to reduce development of COVID 19. According to our knowledge FeMToCOVID will be the first clinical trial with using of FMT in COVID 19. We postulate FMT in the beginning of cytokine storm during CIVUD-19 may act as an immunomodulation and stop the progression of the disease.

Conditions

Covid19

Keywords

COVID 19; FMT; fecal microbiota transplantation; MBiotix HBI; gut-lung axis

Outcome Measures

Primary Outcomes (2)

• Incidence of adverse events after administration of IMP in the phase II/III

  The incidence of adverse events up to day 30 after administration of the product in the safety pilot group

  30 days

• Percentage of patients requiring escalation of oxygen therapy in non-invasive and invasive methods in phase III

  Percentage of patients in the study and control groups requiring escalation of oxygen therapy in non-invasive methods (increasing FiO2 and / or the use of HFNOT and / or other non-invasive methods, e.g. CPAP) and / or invasive ventilation, ventilator therapy and / or hospitalization in the intensive care unit (corresponding to disease exacerbation at grade 5-7 on the COVID-19 Performance Status scale)

  100 days

Secondary Outcomes (13)

• Mortality during hospitalization, up to 14, 30, 60 and 100 days of observation in the study and control groups,

  14, 30, 60, 100 days

• The number of complications secondary to COVID-19 (bacterial, fungal infections, sepsis, septic shock, multi-organ failure) by the 30th day of observation;

  30 days

• COVID-19 Performance Status score during hospitalization from randomization to discharge from hospital or death, and to day 14 and 30 of observation in the study and control groups

  14, 30 days

• The maximum degree of COVID-19 disease severity assessed in the COVID-19 Performance Status scale during hospitalization (until discharge from hospital or death)

  until discharge or death

• NEWS (National Early Warning Score) 2 scores during hospitalization from randomization to discharge from hospital or death in the study and control groups

  until discharge or death

Study Arms (2)

A - SOC+IMP

EXPERIMENTAL

The FMT (fecal microbiota transplantation) will be administered along with the standard COVID 19 pharmacological treatment (SOC- Standard of care). The FMT will be administered orally in one dose - in double cover, gastro-resistant, enteric release capsules in 60g dose (about 30-50 frozen capsules).

Drug: Human fecal microbiota, MBiotix HBI; Drug: SOC

B - SOC+placebo

PLACEBO COMPARATOR

Using standard COVID 19 pharmacological treatment (SOC- Standard of care). The placebo will be administered orally in one dose - in double cover, gastro-resistant, enteric release capsules with lactose (about 30-50 frozen capsules).

Drug: Placebo; Drug: SOC

Interventions

Human fecal microbiota, MBiotix HBI DRUG

The FMT will be administered orally in double cover, gastro-resistant, enteric release capsules in 60g dose (about 30-50 frozen capsules).

Also known as: MBiotix HBI

A - SOC+IMP

Placebo DRUG

Double cover, gastro-resistant, enteric release capsules with lactose (about 30-50 frozen capsules)

B - SOC+placebo

SOC DRUG

The standard COVID 19 pharmacological treatment

A - SOC+IMP; B - SOC+placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Subject has signed Informed Consent Form and is able to understand the purpose and procedures required for the study and is willing to participate in the study.
• Male or female in aged 18 and older.
• Expected survival time, not taking into account SARSCoV2 infection, is at least 6 months.
• Diagnosis of COVID 19 disease confirmed by SARSCoV2 PCR test (the validity of test 7 days before the start of screening).
• Hospitalization due to COVID 19 disease or disease with accompanied COVID 19.
• Any of the following: use of oxygen therapy or oxygen therapy and remdesivir or use of oxygen therapy and convalescent plasma or use of oxygen therapy and remdesivir and convalescents plasma or no necessity of using oxygen therapy but necessity of using remdesivir or convalescents plasma or remdesivir and convalescents plasma (which corresponds to the disease severity of 4-6 points in COVID 19 Performance Status Scale).
• Initially escalated inflammatory process, defined as compliance at least 2 parameters from group "A", during 24 hours before including patient to the study or at least one parameter from group "B".
• Group "A":
• Plasma Amyloid A to lymphocyte count Ratio is greater than 100 (SAA/L\>100)
• SAA \>100mg/l
• Leukocytosis (WBC) over 10 k/ul with absolute lymphopenia under 1,0 k/ul
• CRP \>100 mg/l and absolute lymphopenia
• IL-6 \>25 pg/ml
• Inflammatory changes in lung assessed based on high resolution computed tomography (HRCT) at least 2 points in COVID-CT scale.
• Group "B":

You may not qualify if:

• Age \< 18 years old.
• Inability to obtain Informed Consent.
• Patient's impaired consciousness in opinion of investigator.
• Swallowing difficulties before SARS-CoV 2 infection or related to SASRS-CoV 2 infection (eg. Caused by dyspnea).
• Severe food allergy.
• At least 7 points in COVID-19 Performance Status.
• Significant intestinal passage disturbance, eg. bowel irritation, bowel obstruction, after bowel or stomach resection etc. diagnosed before COVID 19 diagnosis.
• Stoma, perforation or abscess located in gastrointestinal tract area in the past.
• Clinical significant systemic or localised infections, other than COVID 19, eg. lung abscess, pleural abscess, hepatitis, tuberculosis, sepsis ect.
• Severe cardiac failure (NYHA III or more) before COVID 19 diagnosis.
• Significant higher liver parameters: alanine aminotransferase or aspartate aminotransferase \> 500 U/l.
• Important primary or secondary immune dysfunction - eg. AIDS, severe neutropenia (neutrophiles \< 0,5k/ul), inborn immunodeficiency, myelosuppression after chemotherapy etc.
• Female in reproductive age with positive pregnancy test during screening.
• Breast-feeding female.
• Female after menopause:

Sponsors & Collaborators

• Medical University of Warsaw: lead
• Human Biome Institute S.A.: collaborator

MeSH Terms

Conditions

COVID-19

Condition Hierarchy (Ancestors)

Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Infections; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases

Study Officials

• Jarosław Biliński, MD, PhD

  Medical University of Warsaw

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Jarosław Biliński, MD, PhD

CONTACT

0048225992818; jaroslaw.bilinski@gmail.com

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: Phase II/III - open label Phase III - double blind
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Phase II/III : 20 subjects - standard of care (SOC) + FMT capsules Phase III : 173 subjects - arm with SOC + FMT capsules 173 subjects - arm with SOC + Placebo capsules

Study Record Dates

• First Submitted: March 26, 2021
• First Posted: April 1, 2021
• Study Start: April 1, 2021
• Primary Completion: July 1, 2022
• Study Completion: December 1, 2022
• Last Updated: April 1, 2021

Record last verified: 2021-03