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Post COVID-19 Syndrome and the Gut-lung Axis

Primary Purpose

Covid19

Status
Active
Phase
Not Applicable
Locations
Austria
Study Type
Interventional
Intervention
Omni-Biotic Pro Vi 5
Placebo
Sponsored by
Medical University of Graz
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional other trial for Covid19

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesAccepts Healthy Volunteers

Inclusion Criteria:

  • 18 years or older
  • Covid-19 infection with severe disease defined within the last 12 months (defined as one or more of the following: hospitalization, need for oxygen supply, need for intensive care treatment, need for specific treatment of Covid disease, antibiotic treatment)
  • Subjective presence of residual symptoms of Covid disease OR no residual symptoms of Covid disease (Controls)
  • Informed consent

Exclusion Criteria:

  • Continuous probiotic treatment in the last 4 weeks before inclusion
  • Pre-existing lung diseases

Sites / Locations

  • Medical University Graz

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Placebo Comparator

Arm Label

Synbiotic

Placebo

Arm Description

Omni-Biotic Pro Vi 5

similar looking and tasting

Outcomes

Primary Outcome Measures

Microbiome composition
16 sRNA sequencing
Intestinal barrier
Change in zonulin levels over time and with/without the intervention
sCD14
Change in sCD14 levels over time and with/without the intervention
endotoxin
Change in endotoxin levels serum over time and with/without the intervention
TNFalpha
Change in TNFalpha levels serum over time and with/without the intervention
Interleukin 1b
Change in Interleukin 1b serum levels over time and with/without the intervention
Interleukin 6
Change in interleukin 6 serum levels over time and with/without the intervention
Interleukin 6 receptor
Change in Interleukin 6 receptor serum levels over time and with/without the intervention
interleukin 8
Change in interleukin 8 serum levels over time and with/without the intervention
interleukin 10
Change in interleukin 10 serum levels over time and with/without the intervention
interleukin 17
Change in interleukin 17 serum levels over time and with/without the intervention
interleukin 23
Change in interleukin 23 serum levels over time and with/without the intervention
neutrophil function burst function
Change in neutrophil burst function over time and with/without the intervention
neutrophil function phagocytosis
Change in neutrophil phagocytosis function over time and with/without the intervention
neutrophil NET formation
Change in neutrophil NET formation over time and with/without the intervention
neutrophil surface receptor expression
Change in neutrophil surface receptor expression over time and with/without the intervention
monocyte burst
Change in monocyte burst over time and with/without the intervention
monocyte phagocytosis
Change in monocyte phagocytosis over time and with/without the intervention
monocyte function surface receptor expression
Change in monocyte surface receptor expression over time and with/without the intervention
T cell immunophenotyping
Change in T cell subtypes over time and with/without the intervention
B cells immunophenotyping
Change in B cell subtypes over time and with/without the intervention
Spirometry
Change in spirometry measurements over time and with/without the intervention
Lung volume
Change in lung volume over time and with/without the intervention
Gas diffusion
Change in pulmonary gas diffusion over time and with/without the intervention

Secondary Outcome Measures

Full Information

First Posted
March 15, 2021
Last Updated
February 13, 2023
Sponsor
Medical University of Graz
Collaborators
CBmed Ges.m.b.H.
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1. Study Identification

Unique Protocol Identification Number
NCT04813718
Brief Title
Post COVID-19 Syndrome and the Gut-lung Axis
Official Title
Post COVID-19 Syndrome: A Pilot Study to Explore the Gut-lung Axis
Study Type
Interventional

2. Study Status

Record Verification Date
September 2022
Overall Recruitment Status
Active, not recruiting
Study Start Date
June 2, 2021 (Actual)
Primary Completion Date
July 11, 2022 (Actual)
Study Completion Date
December 31, 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Medical University of Graz
Collaborators
CBmed Ges.m.b.H.

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
The outbreak of the novel coronavirus (SARS-CoV-2)-infected disease (COVID-19) began in December 2019, spread throughout China in early 2020 and developed as a pandemic thereafter. Based on current knowledge, Covid-19 infection causes mild to moderate respiratory and gastrointestinal symptoms in the majority of patients. In a smaller percentage severe disease courses are observed, often with the need of hospitalization and intensive care treatment. Apparently, symptoms can persist for relatively long time after viral clearance, suggesting the existence of a "Post-Covid" syndrome. A study from the UK identified fatigue, breathlessness and psychosocial stress as common symptoms after discharge from the hospital. Covid-19 infection is frequently characterized by a hyperinflammatory phenotype and a cytokine storm. The Covid-19 cytokine storm is characterised by rapid proliferation and hyperactivation of T cells, macrophages, mast cells, neutrophil granulocytes and natural killer cells, and the overproduction of inflammatory cytokines and chemical mediators released by immune or nonimmune cells. Early data also suggest that even if symptoms are just 'mild to moderate' during the acute infection, fibrotic lung damage develops in some patients. This may lead to long-term pulmonary complications for a subset of patients. The mechanisms for post-Covid pulmonary fibrosis are still unclear: inflammation triggering fibrosis, epithelial and endothelial injury with inadequate fibroproliferation and vascular damage are considered to be possible mechanisms. A potential therapeutic target in ameliorating post-Covid symptoms could be the gut microbiome. Gut microbiome alterations have been described in Covid-19. The gut-lung axis as a link between dysbiosis, barrier dysfunction, translocation of bacterial products and hyperinflammation has been proposed as a potential therapeutic target. Probiotics have been proposed to be a possible modulator of the deranged gut-lung axis in Covid-disease and post-Covid syndrome. Currently 11 studies are registered in clinicaltrials.gov for treatment of acute Covid disease and prevention of the disease (including one study from Graz), but no study related to post-Covid syndrome could be found. Therefore, it is currently unclear, which clinical, immune system or microbiome related biomarker would be the best to study the effect of a microbiome-based intervention in post-Covid syndrome.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Covid19

7. Study Design

Primary Purpose
Other
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
20 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Synbiotic
Arm Type
Active Comparator
Arm Description
Omni-Biotic Pro Vi 5
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
similar looking and tasting
Intervention Type
Dietary Supplement
Intervention Name(s)
Omni-Biotic Pro Vi 5
Intervention Description
Pre- and probiotic
Intervention Type
Dietary Supplement
Intervention Name(s)
Placebo
Intervention Description
Placebo
Primary Outcome Measure Information:
Title
Microbiome composition
Description
16 sRNA sequencing
Time Frame
6 months
Title
Intestinal barrier
Description
Change in zonulin levels over time and with/without the intervention
Time Frame
6 months
Title
sCD14
Description
Change in sCD14 levels over time and with/without the intervention
Time Frame
6 months
Title
endotoxin
Description
Change in endotoxin levels serum over time and with/without the intervention
Time Frame
6 months
Title
TNFalpha
Description
Change in TNFalpha levels serum over time and with/without the intervention
Time Frame
6 months
Title
Interleukin 1b
Description
Change in Interleukin 1b serum levels over time and with/without the intervention
Time Frame
6 months
Title
Interleukin 6
Description
Change in interleukin 6 serum levels over time and with/without the intervention
Time Frame
6 months
Title
Interleukin 6 receptor
Description
Change in Interleukin 6 receptor serum levels over time and with/without the intervention
Time Frame
6 months
Title
interleukin 8
Description
Change in interleukin 8 serum levels over time and with/without the intervention
Time Frame
6 months
Title
interleukin 10
Description
Change in interleukin 10 serum levels over time and with/without the intervention
Time Frame
6 months
Title
interleukin 17
Description
Change in interleukin 17 serum levels over time and with/without the intervention
Time Frame
6 months
Title
interleukin 23
Description
Change in interleukin 23 serum levels over time and with/without the intervention
Time Frame
6 months
Title
neutrophil function burst function
Description
Change in neutrophil burst function over time and with/without the intervention
Time Frame
6 months
Title
neutrophil function phagocytosis
Description
Change in neutrophil phagocytosis function over time and with/without the intervention
Time Frame
6 months
Title
neutrophil NET formation
Description
Change in neutrophil NET formation over time and with/without the intervention
Time Frame
6 months
Title
neutrophil surface receptor expression
Description
Change in neutrophil surface receptor expression over time and with/without the intervention
Time Frame
6 months
Title
monocyte burst
Description
Change in monocyte burst over time and with/without the intervention
Time Frame
6 months
Title
monocyte phagocytosis
Description
Change in monocyte phagocytosis over time and with/without the intervention
Time Frame
6 months
Title
monocyte function surface receptor expression
Description
Change in monocyte surface receptor expression over time and with/without the intervention
Time Frame
6 months
Title
T cell immunophenotyping
Description
Change in T cell subtypes over time and with/without the intervention
Time Frame
6 months
Title
B cells immunophenotyping
Description
Change in B cell subtypes over time and with/without the intervention
Time Frame
6 months
Title
Spirometry
Description
Change in spirometry measurements over time and with/without the intervention
Time Frame
6 months
Title
Lung volume
Description
Change in lung volume over time and with/without the intervention
Time Frame
6 months
Title
Gas diffusion
Description
Change in pulmonary gas diffusion over time and with/without the intervention
Time Frame
6 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria: 18 years or older Covid-19 infection with severe disease defined within the last 12 months (defined as one or more of the following: hospitalization, need for oxygen supply, need for intensive care treatment, need for specific treatment of Covid disease, antibiotic treatment) Subjective presence of residual symptoms of Covid disease OR no residual symptoms of Covid disease (Controls) Informed consent Exclusion Criteria: Continuous probiotic treatment in the last 4 weeks before inclusion Pre-existing lung diseases
Facility Information:
Facility Name
Medical University Graz
City
Graz
Country
Austria

12. IPD Sharing Statement

Plan to Share IPD
No
IPD Sharing Plan Description
Data will be shared upon reasonable request

Learn more about this trial

Post COVID-19 Syndrome and the Gut-lung Axis

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