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

Covid19 Clinical Trial

Official title:

Exploratory Study on the Effects of Probiotic Supplementation on SARS-CoV-2 Antibody Response in Healthy Adults

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04734886
• Other study ID #: Provid
• Status: Completed
• Phase: N/A
• Start date: November 27, 2020
• Est. completion date: September 13, 2021

Study information

• Verified date: September 2021
• Source: Örebro University, Sweden
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 161
• Est. completion date: September 13, 2021
• Est. primary completion date: September 13, 2021
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 60 Years

Eligibility

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

Related Conditions & MeSH terms

• COVID-19
• Covid19

Intervention

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 + 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

Locations

Country	Name	City	State
Sweden	Örebro University	Örebro	Örebro Län

Sponsors (2)

Lead Sponsor	Collaborator
Örebro University, Sweden	BioGaia AB

Country where clinical trial is conducted

Sweden, 

References & Publications (2)

Lehtoranta L, Pitkäranta 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. Review. — View 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. Review. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Composition of intestinal microbiota and COVID-19 related symptoms	Correlation of intestinal microbiota composition to duration and severity of COVID-19 related symptoms	3 months + 6 months
Other	Composition of intestinal microbiota and SARS-CoV-2 specific antibody	Correlation of intestinal microbiota composition to SARS-CoV-2 specific antibody levels in serum	3 months + 6 months
Other	Composition of intestinal microbiota and inflammatory profile	Correlation of intestinal microbiota composition to TNF-a, IFN-y, IL-1B, IL-4, IL-6, IL-8, IL-10 levels in serum	3 months + 6 months
Primary	SARS-CoV-2 specific antibodies	Change in SARS-CoV-2 specific IgG/IgM antibodies in serum between the study arms	3 months (interim analysis) or at 6 months
Secondary	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	3 months + 6 months
Secondary	Duration of COVID-19 symptoms measured by a weekly symptom questionnaire	Change in duration of COVID-19 related symptoms between the study arms	3 months + 6 months
Secondary	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	3 months + 6 months
Secondary	Secretory IgA (sIgA) antibodies	Change in sIgA levels in saliva between the study arms	3 months + 6 months
Secondary	Blood group A antigen antibodies	Change in anti-A levels in serum between the study arms	3 months + 6 months
Secondary	Blood group B antigen antibodies	Change in anti-B levels in serum between the study arms	3 months + 6 months
Secondary	Tn antigen antibodies	Change in anti-Tn levels in serum between the study arms	3 months + 6 months
Secondary	Innate immune system activation	Change in high-sensitive C-reactive protein (hs-CRP) levels in plasma between the study groups	3 months + 6 months
Secondary	Cytokines	Change in TNF-a, IFN-y, IL-1B, IL-4, IL-6, IL-8, IL-10 levels in serum between the study groups	3 months + 6 months
Secondary	Total antibodies	Change in total IgG and IgM levels in serum between the study groups	3 months + 6 months
Secondary	T cell activation	Change in the proportion of SARS-CoV-2 specific T cells of all T cells in blood between the study arms	3 months + 6 months
Secondary	B cell activation	Change in the proportion of SARS-CoV-2 specific B cells of all B cells in blood between the study arms	3 months + 6 months
Secondary	Intestinal inflammation	Change in faecal calprotectin levels between the study arms	3 months + 6 months
Secondary	Intestinal barrier function	Change in I-FABP levels in plasma between the study arms	3 months + 6 months
Secondary	Indirect marker of intestinal permeability	Change in LBP levels in plasma between the study arms	3 months + 6 months