Back to resultsThe Effect of Probiotic Supplementation on SARS-CoV-2 Antibody Response After COVID-19
Primary Purpose
Covid19
Status
Completed
Phase
Not Applicable
Locations
Sweden
Study Type
Interventional
Intervention
L. reuteri DSM 17938 + vitamin D
Placebo + vitamin D
Sponsored by
About this trial
This is an interventional basic science trial for Covid19
Eligibility Criteria
Inclusion Criteria:
- Signed informed consent
- Age between 18-60
Exclusion Criteria:
- Previous diagnosis of COVID-19 (by positive PCR) or previous confirmation of seropositivity to SARS-CoV-2
- Body Mass Index over 35 or under 16
- Current diagnosis of cancer or ongoing cancer treatment in the last 12 months
- Diabetes mellitus
- Cardiovascular disorder in need of pharmaceutical treatment
- Chronic kidney disease
- Chronic lung disease with decreased lung capacity
- Chronic liver disease with liver cirrhosis
- Current diagnosis of dementia, severe depression, major psychiatric disorder, or other incapacity for adequate cooperation
- Chronic neurological/neurodegenerative disease (e.g. Parkinson's disease)
- Decreased function of the adrenal cortex (e.g. Addison's disease)
- Autoimmune disease (e.g. rheumatoid arthritis)
- Chronic pain syndromes (e.g. fibromyalgia)
- Pregnancy or breast-feeding
- Immunodeficiency due to disease or ongoing medical treatment
- Regular intake of anti-inflammatory and/or other immunosuppressive medication within the last 3 months
- Use of anti-depressants within the last 3 months
- Antimicrobial treatment within the last 12 weeks before baseline sampling
- Regular intake of probiotics, as well as nutritional supplements or herb products that might affect intestinal function within the last 4 weeks if the investigator considers that those could affect study outcome
- Inability to maintain current diet and lifestyle during the study period
- Alcohol or drug abuse
- Any clinically significant present or past disease/condition which the investigator considers to possibly interfere with the study outcome or increase the risk for severe form of COVID-19
Sites / Locations
- Örebro University
Arms of the Study
Arm 1
Arm 2
Arm Type
Active Comparator
Placebo Comparator
Arm Label
L. reuteri DSM 17938
Placebo
Arm Description
Probiotic compound
Placebo compound
Outcomes
Primary Outcome Measures
SARS-CoV-2 specific antibodies
Change in SARS-CoV-2 specific IgG/IgM antibodies in serum between the study arms
Secondary Outcome Measures
Maintenance of SARS-CoV-2 seroconversion in seropositive individuals
Change in the maintenance of SARS-CoV-2 specific IgG/IgM antibody levels in serum between the study arms
Duration of COVID-19 symptoms measured by a weekly symptom questionnaire
Change in duration of COVID-19 related symptoms between the study arms
Severity of COVID-19 symptoms measured by Ordinal Scale for Clinical Improvement (scale 0-7, a lower score corresponds to a better outcome)
Change in severity of COVID-19 related symptoms between the study arms
Secretory IgA (sIgA) antibodies
Change in sIgA levels in saliva between the study arms
Blood group A antigen antibodies
Change in anti-A levels in serum between the study arms
Blood group B antigen antibodies
Change in anti-B levels in serum between the study arms
Tn antigen antibodies
Change in anti-Tn levels in serum between the study arms
Innate immune system activation
Change in high-sensitive C-reactive protein (hs-CRP) levels in plasma between the study groups
Cytokines
Change in TNF-a, IFN-y, IL-1B, IL-4, IL-6, IL-8, IL-10 levels in serum between the study groups
Total antibodies
Change in total IgG and IgM levels in serum between the study groups
T cell activation
Change in the proportion of SARS-CoV-2 specific T cells of all T cells in blood between the study arms
B cell activation
Change in the proportion of SARS-CoV-2 specific B cells of all B cells in blood between the study arms
Intestinal inflammation
Change in faecal calprotectin levels between the study arms
Intestinal barrier function
Change in I-FABP levels in plasma between the study arms
Indirect marker of intestinal permeability
Change in LBP levels in plasma between the study arms
Full Information
NCT ID
NCT04734886
First Posted
December 10, 2020
Last Updated
October 14, 2021
Sponsor
Örebro University, Sweden
Collaborators
BioGaia AB
1. Study Identification
Unique Protocol Identification Number
NCT04734886
Brief Title
The Effect of Probiotic Supplementation on SARS-CoV-2 Antibody Response After COVID-19
Official Title
Exploratory Study on the Effects of Probiotic Supplementation on SARS-CoV-2 Antibody Response in Healthy Adults
Study Type
Interventional
2. Study Status
Record Verification Date
September 2021
Overall Recruitment Status
Completed
Study Start Date
November 27, 2020 (Actual)
Primary Completion Date
September 13, 2021 (Actual)
Study Completion Date
September 13, 2021 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Örebro University, Sweden
Collaborators
BioGaia AB
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
This study will explore how a well-known probiotic strain L. reuteri DSM 17938 impacts SARS-CoV-2 specific antibody response upon and after infection in healthy adults.
Detailed Description
After giving their informed consent, the study subjects will complete screening procedures to assess their eligibility for the study (Visit 1). Participants deemed suitable for the study will be randomized into two study arms (placebo, probiotic) before undergoing a baseline visit (Visit 2) before the start of the intervention period. During the 6-month intervention period, the participants will attend study visits at 3 months (Visit 3) into the intervention as well as at the end of intervention (at 6 months, Visit 4). Blood, saliva, and faecal samples will be collected at visits 2-4. In addition to sampling, during the whole intervention period, the participants will fill out a weekly questionnaire in which they are asked to record any possible symptoms of COVID-19. The participants' dietary habits are assessed via a food frequency questionnaire (FFQ) before the start of the intervention period. Also, the participants are asked to maintain their habitual diet and lifestyle as well as not to consume any other probiotic or prebiotic supplements.
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
Basic Science
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
161 (Actual)
8. Arms, Groups, and Interventions
Arm Title
L. reuteri DSM 17938
Arm Type
Active Comparator
Arm Description
Probiotic compound
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Placebo compound
Intervention Type
Dietary Supplement
Intervention Name(s)
L. reuteri DSM 17938 + vitamin D
Intervention Description
1 * 10^8 CFU of L. reuteri DSM 17938 + 10 ug vitamin D3, two capsules per day for 6 months
Intervention Type
Dietary Supplement
Intervention Name(s)
Placebo + vitamin D
Intervention Description
Placebo tablet + 10 ug vitamin D3, Similar in shape and taste to intervention capsules but without the probiotic components, two capsules per day over six weeks
Primary Outcome Measure Information:
Title
SARS-CoV-2 specific antibodies
Description
Change in SARS-CoV-2 specific IgG/IgM antibodies in serum between the study arms
Time Frame
3 months (interim analysis) or at 6 months
Secondary Outcome Measure Information:
Title
Maintenance of SARS-CoV-2 seroconversion in seropositive individuals
Description
Change in the maintenance of SARS-CoV-2 specific IgG/IgM antibody levels in serum between the study arms
Time Frame
3 months + 6 months
Title
Duration of COVID-19 symptoms measured by a weekly symptom questionnaire
Description
Change in duration of COVID-19 related symptoms between the study arms
Time Frame
3 months + 6 months
Title
Severity of COVID-19 symptoms measured by Ordinal Scale for Clinical Improvement (scale 0-7, a lower score corresponds to a better outcome)
Description
Change in severity of COVID-19 related symptoms between the study arms
Time Frame
3 months + 6 months
Title
Secretory IgA (sIgA) antibodies
Description
Change in sIgA levels in saliva between the study arms
Time Frame
3 months + 6 months
Title
Blood group A antigen antibodies
Description
Change in anti-A levels in serum between the study arms
Time Frame
3 months + 6 months
Title
Blood group B antigen antibodies
Description
Change in anti-B levels in serum between the study arms
Time Frame
3 months + 6 months
Title
Tn antigen antibodies
Description
Change in anti-Tn levels in serum between the study arms
Time Frame
3 months + 6 months
Title
Innate immune system activation
Description
Change in high-sensitive C-reactive protein (hs-CRP) levels in plasma between the study groups
Time Frame
3 months + 6 months
Title
Cytokines
Description
Change in TNF-a, IFN-y, IL-1B, IL-4, IL-6, IL-8, IL-10 levels in serum between the study groups
Time Frame
3 months + 6 months
Title
Total antibodies
Description
Change in total IgG and IgM levels in serum between the study groups
Time Frame
3 months + 6 months
Title
T cell activation
Description
Change in the proportion of SARS-CoV-2 specific T cells of all T cells in blood between the study arms
Time Frame
3 months + 6 months
Title
B cell activation
Description
Change in the proportion of SARS-CoV-2 specific B cells of all B cells in blood between the study arms
Time Frame
3 months + 6 months
Title
Intestinal inflammation
Description
Change in faecal calprotectin levels between the study arms
Time Frame
3 months + 6 months
Title
Intestinal barrier function
Description
Change in I-FABP levels in plasma between the study arms
Time Frame
3 months + 6 months
Title
Indirect marker of intestinal permeability
Description
Change in LBP levels in plasma between the study arms
Time Frame
3 months + 6 months
Other Pre-specified Outcome Measures:
Title
Composition of intestinal microbiota and COVID-19 related symptoms
Description
Correlation of intestinal microbiota composition to duration and severity of COVID-19 related symptoms
Time Frame
3 months + 6 months
Title
Composition of intestinal microbiota and SARS-CoV-2 specific antibody
Description
Correlation of intestinal microbiota composition to SARS-CoV-2 specific antibody levels in serum
Time Frame
3 months + 6 months
Title
Composition of intestinal microbiota and inflammatory profile
Description
Correlation of intestinal microbiota composition to TNF-a, IFN-y, IL-1B, IL-4, IL-6, IL-8, IL-10 levels in serum
Time Frame
3 months + 6 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
60 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria:
Signed informed consent
Age between 18-60
Exclusion Criteria:
Previous diagnosis of COVID-19 (by positive PCR) or previous confirmation of seropositivity to SARS-CoV-2
Body Mass Index over 35 or under 16
Current diagnosis of cancer or ongoing cancer treatment in the last 12 months
Diabetes mellitus
Cardiovascular disorder in need of pharmaceutical treatment
Chronic kidney disease
Chronic lung disease with decreased lung capacity
Chronic liver disease with liver cirrhosis
Current diagnosis of dementia, severe depression, major psychiatric disorder, or other incapacity for adequate cooperation
Chronic neurological/neurodegenerative disease (e.g. Parkinson's disease)
Decreased function of the adrenal cortex (e.g. Addison's disease)
Autoimmune disease (e.g. rheumatoid arthritis)
Chronic pain syndromes (e.g. fibromyalgia)
Pregnancy or breast-feeding
Immunodeficiency due to disease or ongoing medical treatment
Regular intake of anti-inflammatory and/or other immunosuppressive medication within the last 3 months
Use of anti-depressants within the last 3 months
Antimicrobial treatment within the last 12 weeks before baseline sampling
Regular intake of probiotics, as well as nutritional supplements or herb products that might affect intestinal function within the last 4 weeks if the investigator considers that those could affect study outcome
Inability to maintain current diet and lifestyle during the study period
Alcohol or drug abuse
Any clinically significant present or past disease/condition which the investigator considers to possibly interfere with the study outcome or increase the risk for severe form of COVID-19
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Robert J Brummer, MD, PhD
Organizational Affiliation
Örebro University, Sweden
Official's Role
Principal Investigator
Facility Information:
Facility Name
Örebro University
City
Örebro
State/Province
Örebro Län
ZIP/Postal Code
703 62
Country
Sweden
12. IPD Sharing Statement
Plan to Share IPD
No
IPD Sharing Plan Description
IPD will not be shared, results will shared only on group-level
Citations:
PubMed Identifier
24638909
Citation
Lehtoranta L, Pitkaranta A, Korpela R. Probiotics in respiratory virus infections. Eur J Clin Microbiol Infect Dis. 2014 Aug;33(8):1289-302. doi: 10.1007/s10096-014-2086-y. Epub 2014 Mar 18.
Results Reference
background
PubMed Identifier
28923425
Citation
Zimmermann P, Curtis N. The influence of probiotics on vaccine responses - A systematic review. Vaccine. 2018 Jan 4;36(2):207-213. doi: 10.1016/j.vaccine.2017.08.069. Epub 2017 Sep 18.
Results Reference
background
Learn more about this trial
The Effect of Probiotic Supplementation on SARS-CoV-2 Antibody Response After COVID-19
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