The Effect of Probiotic Supplementation on SARS-CoV-2 Antibody Response After COVID-19

Sponsor
Örebro University, Sweden (Other)
Overall Status
Completed
CT.gov ID
NCT04734886
Collaborator
BioGaia AB (Industry)
161
1
2
9.5
16.9

Study Details

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.

Condition or Disease Intervention/Treatment Phase
  • Dietary Supplement: L. reuteri DSM 17938 + vitamin D
  • Dietary Supplement: Placebo + vitamin D
N/A

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.

Study Design

Study Type:
Interventional
Actual Enrollment :
161 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose:
Basic Science
Official Title:
Exploratory Study on the Effects of Probiotic Supplementation on SARS-CoV-2 Antibody Response in Healthy Adults
Actual Study Start Date :
Nov 27, 2020
Actual Primary Completion Date :
Sep 13, 2021
Actual Study Completion Date :
Sep 13, 2021

Arms and Interventions

Arm Intervention/Treatment
Active Comparator: L. reuteri DSM 17938

Probiotic compound

Dietary Supplement: L. reuteri DSM 17938 + vitamin D
1 * 10^8 CFU of L. reuteri DSM 17938 + 10 ug vitamin D3, two capsules per day for 6 months

Placebo Comparator: Placebo

Placebo compound

Dietary Supplement: Placebo + vitamin D
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

Outcome Measures

Primary Outcome Measures

  1. SARS-CoV-2 specific antibodies [3 months (interim analysis) or at 6 months]

    Change in SARS-CoV-2 specific IgG/IgM antibodies in serum between the study arms

Secondary Outcome Measures

  1. Maintenance of SARS-CoV-2 seroconversion in seropositive individuals [3 months + 6 months]

    Change in the maintenance of SARS-CoV-2 specific IgG/IgM antibody levels in serum between the study arms

  2. Duration of COVID-19 symptoms measured by a weekly symptom questionnaire [3 months + 6 months]

    Change in duration of COVID-19 related symptoms between the study arms

  3. Severity of COVID-19 symptoms measured by Ordinal Scale for Clinical Improvement (scale 0-7, a lower score corresponds to a better outcome) [3 months + 6 months]

    Change in severity of COVID-19 related symptoms between the study arms

  4. Secretory IgA (sIgA) antibodies [3 months + 6 months]

    Change in sIgA levels in saliva between the study arms

  5. Blood group A antigen antibodies [3 months + 6 months]

    Change in anti-A levels in serum between the study arms

  6. Blood group B antigen antibodies [3 months + 6 months]

    Change in anti-B levels in serum between the study arms

  7. Tn antigen antibodies [3 months + 6 months]

    Change in anti-Tn levels in serum between the study arms

  8. Innate immune system activation [3 months + 6 months]

    Change in high-sensitive C-reactive protein (hs-CRP) levels in plasma between the study groups

  9. Cytokines [3 months + 6 months]

    Change in TNF-a, IFN-y, IL-1B, IL-4, IL-6, IL-8, IL-10 levels in serum between the study groups

  10. Total antibodies [3 months + 6 months]

    Change in total IgG and IgM levels in serum between the study groups

  11. T cell activation [3 months + 6 months]

    Change in the proportion of SARS-CoV-2 specific T cells of all T cells in blood between the study arms

  12. B cell activation [3 months + 6 months]

    Change in the proportion of SARS-CoV-2 specific B cells of all B cells in blood between the study arms

  13. Intestinal inflammation [3 months + 6 months]

    Change in faecal calprotectin levels between the study arms

  14. Intestinal barrier function [3 months + 6 months]

    Change in I-FABP levels in plasma between the study arms

  15. Indirect marker of intestinal permeability [3 months + 6 months]

    Change in LBP levels in plasma between the study arms

Other Outcome Measures

  1. Composition of intestinal microbiota and COVID-19 related symptoms [3 months + 6 months]

    Correlation of intestinal microbiota composition to duration and severity of COVID-19 related symptoms

  2. Composition of intestinal microbiota and SARS-CoV-2 specific antibody [3 months + 6 months]

    Correlation of intestinal microbiota composition to SARS-CoV-2 specific antibody levels in serum

  3. Composition of intestinal microbiota and inflammatory profile [3 months + 6 months]

    Correlation of intestinal microbiota composition to TNF-a, IFN-y, IL-1B, IL-4, IL-6, IL-8, IL-10 levels in serum

Eligibility Criteria

Criteria

Ages Eligible for Study:
18 Years to 60 Years
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
Yes
Inclusion Criteria:
  1. Signed informed consent

  2. Age between 18-60

Exclusion Criteria:
  1. Previous diagnosis of COVID-19 (by positive PCR) or previous confirmation of seropositivity to SARS-CoV-2

  2. Body Mass Index over 35 or under 16

  3. Current diagnosis of cancer or ongoing cancer treatment in the last 12 months

  4. Diabetes mellitus

  5. Cardiovascular disorder in need of pharmaceutical treatment

  6. Chronic kidney disease

  7. Chronic lung disease with decreased lung capacity

  8. Chronic liver disease with liver cirrhosis

  9. Current diagnosis of dementia, severe depression, major psychiatric disorder, or other incapacity for adequate cooperation

  10. Chronic neurological/neurodegenerative disease (e.g. Parkinson's disease)

  11. Decreased function of the adrenal cortex (e.g. Addison's disease)

  12. Autoimmune disease (e.g. rheumatoid arthritis)

  13. Chronic pain syndromes (e.g. fibromyalgia)

  14. Pregnancy or breast-feeding

  15. Immunodeficiency due to disease or ongoing medical treatment

  16. Regular intake of anti-inflammatory and/or other immunosuppressive medication within the last 3 months

  17. Use of anti-depressants within the last 3 months

  18. Antimicrobial treatment within the last 12 weeks before baseline sampling

  19. 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

  20. Inability to maintain current diet and lifestyle during the study period

  21. Alcohol or drug abuse

  22. 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

Contacts and Locations

Locations

Site City State Country Postal Code
1 Örebro University Örebro Örebro Län Sweden 703 62

Sponsors and Collaborators

  • Örebro University, Sweden
  • BioGaia AB

Investigators

  • Principal Investigator: Robert J Brummer, MD, PhD, Örebro University, Sweden

Study Documents (Full-Text)

None provided.

More Information

Publications

Responsible Party:
Örebro University, Sweden
ClinicalTrials.gov Identifier:
NCT04734886
Other Study ID Numbers:
  • Provid
First Posted:
Feb 2, 2021
Last Update Posted:
Oct 15, 2021
Last Verified:
Sep 1, 2021
Individual Participant Data (IPD) Sharing Statement:
No
Plan to Share IPD:
No
Studies a U.S. FDA-regulated Drug Product:
No
Studies a U.S. FDA-regulated Device Product:
No
Additional relevant MeSH terms:

Study Results

No Results Posted as of Oct 15, 2021