Clinical trial NCT04734886: 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
Overall status: COMPLETED
Phase: NA
Conditions: Covid19
Lead sponsor: Örebro University, Sweden
Sponsor class: OTHER
Collaborators: name: BioGaia AB
First posted: 2021-02-02
Enrollment: 161
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

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.

Eligibility criteria: 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

Primary outcomes:
measure: SARS-CoV-2 specific antibodies
timeFrame: 3 months (interim analysis) or at 6 months
Secondary outcomes:
measure: Maintenance of SARS-CoV-2 seroconversion in seropositive individuals
timeFrame: 3 months + 6 months
measure: Duration of COVID-19 symptoms measured by a weekly symptom questionnaire
timeFrame: 3 months + 6 months
measure: Severity of COVID-19 symptoms measured by Ordinal Scale for Clinical Improvement (scale 0-7, a lower score corresponds to a better outcome)
timeFrame: 3 months + 6 months
measure: Secretory IgA (sIgA) antibodies
timeFrame: 3 months + 6 months
measure: Blood group A antigen antibodies
timeFrame: 3 months + 6 months
measure: Blood group B antigen antibodies
timeFrame: 3 months + 6 months
measure: Tn antigen antibodies
timeFrame: 3 months + 6 months
measure: Innate immune system activation
timeFrame: 3 months + 6 months
measure: Cytokines
timeFrame: 3 months + 6 months
measure: Total antibodies
timeFrame: 3 months + 6 months
measure: T cell activation
timeFrame: 3 months + 6 months
measure: B cell activation
timeFrame: 3 months + 6 months
measure: Intestinal inflammation
timeFrame: 3 months + 6 months
measure: Intestinal barrier function
timeFrame: 3 months + 6 months
measure: Indirect marker of intestinal permeability
timeFrame: 3 months + 6 months
Other outcomes:
measure: Composition of intestinal microbiota and COVID-19 related symptoms
timeFrame: 3 months + 6 months
measure: Composition of intestinal microbiota and SARS-CoV-2 specific antibody
timeFrame: 3 months + 6 months
measure: Composition of intestinal microbiota and inflammatory profile
timeFrame: 3 months + 6 months
Locations:
city: Örebro
country: Sweden
facility: Örebro University
state: Örebro Län
Study officials:
affiliation: Örebro University, Sweden
name: Robert J Brummer, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
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.
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.