Back to resultsEffect of a Multi-strain Probiotic Formulation on Immune Response to Influenza Vaccination (FLUVAC21)
Primary Purpose
Influenza Vaccine
Status
Completed
Phase
Not Applicable
Locations
Spain
Study Type
Interventional
Intervention
Food Supplement
Placebo
Sponsored by
About this trial
This is an interventional other trial for Influenza Vaccine focused on measuring influenza vaccination, probiotic
Eligibility Criteria
Inclusion Criteria:
- Subjects 50 - 80 years old receiving seasonal Influenza vaccine in season 2021-2022
- Body mass index (BMI) 18.5-34.9 kg/m2
- Willing to provide informed consent
- Able to follow study procedures, according to the criteria of study investigator
Exclusion Criteria:
- Hypersensitivity to any of the components of influenza vaccine
- Previous influenza infection in the same season (from 01/09/2021)
- Having received influenza vaccination in the previous season less than 9 months before study entry (from 01/01/2021)
- Having received another vaccine -different from COVID19 vaccine- up to 1 month before study inclusion or planning to receive it 1 month after study inclusion
- Active infection at the moment of study entry as diagnosed by study physician
- History of severe allergic reactions (food and non-food), including severe asthma.
- Receiving immunosuppressant therapy, displaying neutropenia, lymphopenia, AIDS, immunoglobulin deficiency, active oncological disease.
- Daily ingestion of any food complement or food added with probiotics (including Actimel o similar products) 2 weeks before inclusion in the study
- Acute pancreatitis, short bowel syndrome or active inflammatory bowel disease
- Diagnosed from other pathologies that according to study physician may compromise the immunological function of the individual (such as immunodeficiencies, lupus, multiple sclerosis, among others)
- Having received antibiotic treatment in the previous month
Exclusion criteria during the study:
- Withdrawal from the study as per study investigator criteria, in case that study procedures are not followed by the participant
- In case of adverse event that prevents them from following study procedures or complying with the treatments under study.
- Failure to comply with study procedures: Complete less than 70% of the days in the patient's diary and/or take less than 80% of the days of the study products.
- Receive any of the unauthorized treatments indicated in the selection criteria, with the exception of antibiotics that will be allowed under medical prescription.
Sites / Locations
- Hospital General de Granollers
- Hospital Parc Tauli
- IDIAP Jordi Gol-Centro de Atención Primaria La Mina
- Mutua de Terrassa
- FIBAO- Fundación para la Investigación Biosanitaria de Andalucia Oriental
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
Experimental
Placebo
Arm Description
Probiotic multi-strain formulation comprising L. plantarum CECT30292, CECT7484, CECT7585 and P. acidilactici and maltodextrin (E1400, qs) as excipient in hydroxymethylpropyl-cellulose (HPMC) capsules. Probiotic strains have Qualified Presumption of Safety (QPS) status by European Food Safety Authority
Maltodextrin (E1400, qs) in HPMC capsules
Outcomes
Primary Outcome Measures
IgG antibodies against vaccine influenza antigens
Titer of specific total IgG antibodies against vaccine influenza A and B antigens at day 28
Secondary Outcome Measures
IgG antibodies against vaccine influenza antigens
Titer of specific total IgG antibodies against vaccine influenza A and B antigens at day 56
IgM antibodies against vaccine influenza antigens
Titer of specific total IgM antibodies against vaccine influenza A and B antigens at day 28 and 56
Seroconversion
Percentage of patients with seroconversion (defined as 4 fold change in influenza IgG antibodies concentration compared to baseline) at day 28 and 56
Incidence of influenza like infections (ILI)
Cumulative incidence of influenza like infection (ILI), according to the European Diseases Prevention and Control Center (ECDC) criteria
Incidence of any other respiratory infections (including COVID-19)
Cumulative incidence of any other respiratory infections
Incidence of fever
Cumulative number of days with fever (> 37.5ºC)
Use of analgesics and antibiotics
Cumulative number of days using analgesics and antibiotics
Duration of vaccine-related symptoms: injection-site pain, swelling, redness
Duration (in days) of symptoms after receiving the flu vaccine.
Severity of vaccine-related symptoms: injection-site pain, swelling, redness
Severity of symptoms after receiving the flu vaccine. Measured on a 4-point scale: 0 = none , 1 = mild, 2 = moderate, and 3 = severe
Gastrointestinal symptoms
Gastrointestinal manifestations documented through questionnaire in participants diary. Measured on a 4-point scale: 0 = none , 1 = mild, 2 = moderate, and 3 = severe.
Adverse events
Frequency of adverse events reported in medical visits or patient diary
Albumin
Albumin concentration in blood
Alkaline phosphatase (ALP)
Alkaline phosphatase (ALP) concentration in blood
Gamma-glutamil transpeptidase (GGT)
Gamma-glutamil transpeptidase (GGT) concentration in blood
Aspartate aminotransferase (GOT)
Aspartate aminotransferase (AST) concentration in blood
Alanine aminotransferase (AST)
Aspartate aminotransferase (AST) concentration in blood
Basic hemogram
Blood cell count
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT05157425
Brief Title
Effect of a Multi-strain Probiotic Formulation on Immune Response to Influenza Vaccination
Acronym
FLUVAC21
Official Title
Efficacy and Safety of a Multistrain Probiotic Formula to Boost the Immune Response to Influenza Virus Vaccination
Study Type
Interventional
2. Study Status
Record Verification Date
July 2022
Overall Recruitment Status
Completed
Study Start Date
October 26, 2021 (Actual)
Primary Completion Date
February 28, 2022 (Actual)
Study Completion Date
May 31, 2022 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
AB Biotics, SA
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
Randomized clinical trial to determine whether a probiotic formulation containing 4 probiotic strains which belong to Lactiplantibacillus plantarum and Pediococcus acidilactici species can boost the immune response to influenza vaccination evaluated at 4 weeks in a population between 50 and 80 years of age. Secondary outcomes comprise evaluation of immune response at 8 weeks after vaccination, percentage of patients with seroconversion, incidence and duration of influenza-like infections and respiratory infections throughout a 4-month period and safety.
Detailed Description
Double blind, randomized, placebo-controlled clinical trial to determine whether supplementation with a probiotic formulation containing 4 probiotic strains (L. plantarum CECT 30292, CECT7484, CECT7485 and P. acidilactici CECT7483) can improve immune response to seasonal influenza vaccination. Subjects with age comprised between 50 and 80 years who meet inclusion and exclusion criteria will be randomized 1:1 to one of the following study groups: one will receive probiotic formulation for 28 days (1 capsule/day) and the other will receive placebo, starting the same day of the influenza vaccination. Main study outcome will be immune response at 4 weeks after vaccination, which will be determined by analysis of specific IgG antibodies in serum against influenza A and B. Secondary outcomes comprise serum titers of specific IgG at 8 weeks after vaccination, percentage of patients with seroconversion at 4 and 8 weeks, evaluation of influenza-like infections or respiratory infections throughout a 4-month period and adverse events.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Influenza Vaccine
Keywords
influenza vaccination, probiotic
7. Study Design
Primary Purpose
Other
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Model Description
Double blind, randomized controlled trial in 140 subjects 50-80 years old receiving influenza vaccination, who will be allocated to receive either an experimental product containing multi-strain probiotic formula or placebo for 28 days
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Masking Description
Both placebo and active product will be provided in identical packaging.
Allocation
Randomized
Enrollment
140 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Experimental
Arm Type
Experimental
Arm Description
Probiotic multi-strain formulation comprising L. plantarum CECT30292, CECT7484, CECT7585 and P. acidilactici and maltodextrin (E1400, qs) as excipient in hydroxymethylpropyl-cellulose (HPMC) capsules. Probiotic strains have Qualified Presumption of Safety (QPS) status by European Food Safety Authority
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Maltodextrin (E1400, qs) in HPMC capsules
Intervention Type
Dietary Supplement
Intervention Name(s)
Food Supplement
Other Intervention Name(s)
Probiotic
Intervention Description
Probiotic multistrain formulation containing Lactiplantibacillus plantarum CECT30292, CECT7484, CECT7485 and P. acidilactici CECT7483 for 28 days, starting the same day of influenza vaccination
Intervention Type
Dietary Supplement
Intervention Name(s)
Placebo
Intervention Description
One maltodextrin-containing capsule/day for 28 days, starting the same day of influenza vaccination
Primary Outcome Measure Information:
Title
IgG antibodies against vaccine influenza antigens
Description
Titer of specific total IgG antibodies against vaccine influenza A and B antigens at day 28
Time Frame
4 weeks (day 1 and day 28)
Secondary Outcome Measure Information:
Title
IgG antibodies against vaccine influenza antigens
Description
Titer of specific total IgG antibodies against vaccine influenza A and B antigens at day 56
Time Frame
8 weeks (day 1 and day 56)
Title
IgM antibodies against vaccine influenza antigens
Description
Titer of specific total IgM antibodies against vaccine influenza A and B antigens at day 28 and 56
Time Frame
8 weeks (day 1 and day 56)
Title
Seroconversion
Description
Percentage of patients with seroconversion (defined as 4 fold change in influenza IgG antibodies concentration compared to baseline) at day 28 and 56
Time Frame
8 weeks (day 1,day 28 and 56)
Title
Incidence of influenza like infections (ILI)
Description
Cumulative incidence of influenza like infection (ILI), according to the European Diseases Prevention and Control Center (ECDC) criteria
Time Frame
16 weeks (day 1, day 56)
Title
Incidence of any other respiratory infections (including COVID-19)
Description
Cumulative incidence of any other respiratory infections
Time Frame
16 weeks (day 1, day 56)
Title
Incidence of fever
Description
Cumulative number of days with fever (> 37.5ºC)
Time Frame
16 weeks (day 1, day 56)
Title
Use of analgesics and antibiotics
Description
Cumulative number of days using analgesics and antibiotics
Time Frame
16 weeks (day 1, day 56)
Title
Duration of vaccine-related symptoms: injection-site pain, swelling, redness
Description
Duration (in days) of symptoms after receiving the flu vaccine.
Time Frame
1 week (day 1, day 7)
Title
Severity of vaccine-related symptoms: injection-site pain, swelling, redness
Description
Severity of symptoms after receiving the flu vaccine. Measured on a 4-point scale: 0 = none , 1 = mild, 2 = moderate, and 3 = severe
Time Frame
1 week (day 1, day 7)
Title
Gastrointestinal symptoms
Description
Gastrointestinal manifestations documented through questionnaire in participants diary. Measured on a 4-point scale: 0 = none , 1 = mild, 2 = moderate, and 3 = severe.
Time Frame
4 weeks (day 1, day 28)
Title
Adverse events
Description
Frequency of adverse events reported in medical visits or patient diary
Time Frame
8 weeks (day 56)
Title
Albumin
Description
Albumin concentration in blood
Time Frame
4 weeks (day 1, day 28)
Title
Alkaline phosphatase (ALP)
Description
Alkaline phosphatase (ALP) concentration in blood
Time Frame
4 weeks (day 1, day 28)
Title
Gamma-glutamil transpeptidase (GGT)
Description
Gamma-glutamil transpeptidase (GGT) concentration in blood
Time Frame
4 weeks (day 1, day 28)
Title
Aspartate aminotransferase (GOT)
Description
Aspartate aminotransferase (AST) concentration in blood
Time Frame
4 weeks (day 1, day 28)
Title
Alanine aminotransferase (AST)
Description
Aspartate aminotransferase (AST) concentration in blood
Time Frame
4 weeks (day 1, day 28)
Title
Basic hemogram
Description
Blood cell count
Time Frame
4 weeks (day 1, day 28)
10. Eligibility
Sex
All
Minimum Age & Unit of Time
50 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria:
Subjects 50 - 80 years old receiving seasonal Influenza vaccine in season 2021-2022
Body mass index (BMI) 18.5-34.9 kg/m2
Willing to provide informed consent
Able to follow study procedures, according to the criteria of study investigator
Exclusion Criteria:
Hypersensitivity to any of the components of influenza vaccine
Previous influenza infection in the same season (from 01/09/2021)
Having received influenza vaccination in the previous season less than 9 months before study entry (from 01/01/2021)
Having received another vaccine -different from COVID19 vaccine- up to 1 month before study inclusion or planning to receive it 1 month after study inclusion
Active infection at the moment of study entry as diagnosed by study physician
History of severe allergic reactions (food and non-food), including severe asthma.
Receiving immunosuppressant therapy, displaying neutropenia, lymphopenia, AIDS, immunoglobulin deficiency, active oncological disease.
Daily ingestion of any food complement or food added with probiotics (including Actimel o similar products) 2 weeks before inclusion in the study
Acute pancreatitis, short bowel syndrome or active inflammatory bowel disease
Diagnosed from other pathologies that according to study physician may compromise the immunological function of the individual (such as immunodeficiencies, lupus, multiple sclerosis, among others)
Having received antibiotic treatment in the previous month
Exclusion criteria during the study:
Withdrawal from the study as per study investigator criteria, in case that study procedures are not followed by the participant
In case of adverse event that prevents them from following study procedures or complying with the treatments under study.
Failure to comply with study procedures: Complete less than 70% of the days in the patient's diary and/or take less than 80% of the days of the study products.
Receive any of the unauthorized treatments indicated in the selection criteria, with the exception of antibiotics that will be allowed under medical prescription.
Facility Information:
Facility Name
Hospital General de Granollers
City
Granollers
State/Province
Barcelona
ZIP/Postal Code
08401
Country
Spain
Facility Name
Hospital Parc Tauli
City
Sabadell
State/Province
Barcelona
ZIP/Postal Code
08208
Country
Spain
Facility Name
IDIAP Jordi Gol-Centro de Atención Primaria La Mina
City
Sant Adrià De Besòs
State/Province
Barcelona
ZIP/Postal Code
08930
Country
Spain
Facility Name
Mutua de Terrassa
City
Terrassa
State/Province
Barcelona
ZIP/Postal Code
08221
Country
Spain
Facility Name
FIBAO- Fundación para la Investigación Biosanitaria de Andalucia Oriental
City
Granada
ZIP/Postal Code
18002
Country
Spain
12. IPD Sharing Statement
Plan to Share IPD
No
Citations:
PubMed Identifier
23002979
Citation
Lambert ND, Ovsyannikova IG, Pankratz VS, Jacobson RM, Poland GA. Understanding the immune response to seasonal influenza vaccination in older adults: a systems biology approach. Expert Rev Vaccines. 2012 Aug;11(8):985-94. doi: 10.1586/erv.12.61.
Results Reference
background
PubMed Identifier
30551178
Citation
Ng TWY, Cowling BJ, Gao HZ, Thompson MG. Comparative Immunogenicity of Enhanced Seasonal Influenza Vaccines in Older Adults: A Systematic Review and Meta-analysis. J Infect Dis. 2019 Apr 19;219(10):1525-1535. doi: 10.1093/infdis/jiy720.
Results Reference
background
PubMed Identifier
33643929
Citation
Harper A, Vijayakumar V, Ouwehand AC, Ter Haar J, Obis D, Espadaler J, Binda S, Desiraju S, Day R. Viral Infections, the Microbiome, and Probiotics. Front Cell Infect Microbiol. 2021 Feb 12;10:596166. doi: 10.3389/fcimb.2020.596166. eCollection 2020.
Results Reference
background
PubMed Identifier
30019448
Citation
Trombetta CM, Remarque EJ, Mortier D, Montomoli E. Comparison of hemagglutination inhibition, single radial hemolysis, virus neutralization assays, and ELISA to detect antibody levels against seasonal influenza viruses. Influenza Other Respir Viruses. 2018 Nov;12(6):675-686. doi: 10.1111/irv.12591. Epub 2018 Aug 11.
Results Reference
background
PubMed Identifier
34002068
Citation
Lynn DJ, Benson SC, Lynn MA, Pulendran B. Modulation of immune responses to vaccination by the microbiota: implications and potential mechanisms. Nat Rev Immunol. 2022 Jan;22(1):33-46. doi: 10.1038/s41577-021-00554-7. Epub 2021 May 17.
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
result
PubMed Identifier
29416317
Citation
Yeh TL, Shih PC, Liu SJ, Lin CH, Liu JM, Lei WT, Lin CY. The influence of prebiotic or probiotic supplementation on antibody titers after influenza vaccination: a systematic review and meta-analysis of randomized controlled trials. Drug Des Devel Ther. 2018 Jan 25;12:217-230. doi: 10.2147/DDDT.S155110. eCollection 2018.
Results Reference
result
PubMed Identifier
33578007
Citation
Darbandi A, Asadi A, Ghanavati R, Afifirad R, Darb Emamie A, Kakanj M, Talebi M. The effect of probiotics on respiratory tract infection with special emphasis on COVID-19: Systemic review 2010-20. Int J Infect Dis. 2021 Apr;105:91-104. doi: 10.1016/j.ijid.2021.02.011. Epub 2021 Feb 9. Erratum In: Int J Infect Dis. 2021 Sep;110:337.
Results Reference
result
Learn more about this trial
Effect of a Multi-strain Probiotic Formulation on Immune Response to Influenza Vaccination
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