Efficacy and Safety of Oral Lactobacillus Plantarum GUANKE (CGMCC NO.21720) in Enhancement of Antibody Level After SARS-CoV-2 Vaccination (Trial 2)

Study Overview
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Brief Summary
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Preliminarily explore the effect of oral probiotics in SARS-CoV-2 serum neutralizing antibody titer level and T cell response level (spot formation cell counting). Provide a reference for determining the appropriate oral regimen. Provide necessary parameters for estimating the sample size of confirmatory clinical trial.

Detailed Description
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In selected communities or assigned clinical trial institutions, participants who intend to complete the third dose of SARS-CoV-2 vaccination will be invited in this study. Informed consent form will give to potential participants with well explained of trial contents during baseline. Participants who gave their signed informed consent form will be blocked randomized in a 1:1:1:1 ratio to intervention group A, intervention group B, intervention group C, or placebo group D.

Official Title
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Efficacy and Safety of Oral Lactobacillus Plantarum GUANKE (CGMCC NO.21720) in Enhancement of Antibody Level After SARS-CoV-2 Vaccination: A Prospective, Randomized, Double-blind, Placebo-Controlled Trial (Trial 2)

Conditions
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SARS-CoV-2

Intervention / Treatment
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* Dietary Supplement: 1 week placebo(Week 1)
* Dietary Supplement: 1 week of probiotics(Week 1)
* Dietary Supplement: 1 week placebo(Week 2)
* Dietary Supplement: 1 week of probiotics(Week 2)
* Dietary Supplement: 1 week placebo(Week 3)
* Dietary Supplement: 1 week of probiotics(Week 3)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 18 ≤age ≤59 years; Vaccinated with two doses of SARS-CoV-2 vaccine (manufactured by Sino Biopharmaceutical Limited or SINOVAC BIOTECH CO., LTD.) (≥6 months from the time of vaccination). Plan to vaccinate third dose vaccination (manufactured by Sino Biopharmaceutical Limited or SINOVAC BIOTECH CO., LTD.); Voluntarily participate in the study with signed informed consent form. Exclusion criteria: Pregnancy or lactation period; Infected with human immunodeficiency virus (HIV), hepatitis B virus (HBV) or hepatitis C virus (HCV); History of autoimmune diseases (e.g. rheumatoid arthritis, systemic lupus erythematosus, dry syndrome, etc.); Previously infected with SARS-CoV-2 or close contact of SARS-CoV-2 infected individual; Other SARS-CoV-2 vaccination history (not manufactured by Sino Biopharmaceutical Limited or SINOVAC BIOTECH CO., LTD.); End-stage cancer or other terminal diseases with life expectancy <6 month; History of severe cardiovascular and cerebrovascular diseases, such as heart failure, uncontrolled coronary heart disease, cardiomyopathy, uncontrolled arrhythmia, or history of myocardial or cerebral infarction within past six months; Participating in other clinical trials.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 59 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: A prospective, randomized, double-blind, placebo parallel controlled clinical trial.
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Probiotics-Placebo-Placebo<br>1 week of consecutively consuming oral probiotics (1 time/day) followed by SARS-CoV-2 vaccination, then 2 weeks of consecutively consuming oral placebo (1 time/day). | Dietary Supplement: 1 week of probiotics(Week 1)<br>* 1 week of consecutively consuming oral probiotics (1 time/day)<br>Dietary Supplement: 1 week placebo(Week 2)<br>* 1 week of consecutively consuming oral placebo (1 time/day)<br>Dietary Supplement: 1 week placebo(Week 3)<br>* 1 week of consecutively consuming oral placebo (1 time/day)<br>|
| Experimental: Placebo-Probiotics-Placebo<br>1 week of consecutively consuming oral placebo (1 time/day) followed by SARS-CoV-2 vaccination, then consuming oral probiotics (1 time/day) for 1 week and placebo (1 time/day) for 1 week (1 time/day) respectively. | Dietary Supplement: 1 week placebo(Week 1)<br>* 1 week of consecutively consuming oral placebo (1 time/day)<br>Dietary Supplement: 1 week of probiotics(Week 2)<br>* 1 week of consecutively consuming oral probiotics (1 time/day)<br>Dietary Supplement: 1 week placebo(Week 3)<br>* 1 week of consecutively consuming oral placebo (1 time/day)<br>|
| Experimental: Placebo-Placebo-Probiotics<br>1 week of consecutively consuming oral placebo (1 time/day) followed SARS-CoV-2 vaccination, then consuming oral placebo for 1 week (1 time/day) and probiotics for 1 week (1 time/day) respectively. | Dietary Supplement: 1 week placebo(Week 1)<br>* 1 week of consecutively consuming oral placebo (1 time/day)<br>Dietary Supplement: 1 week placebo(Week 2)<br>* 1 week of consecutively consuming oral placebo (1 time/day)<br>Dietary Supplement: 1 week of probiotics(Week 3)<br>* 1 week of consecutively consuming oral probiotics (1 time/day)<br>|
| Placebo Comparator: Placebo<br>1 week of consecutively consuming oral placebo (1 time/day) followed by SARS-CoV-2 vaccination, then 2 weeks of consecutively consuming oral placebo (1 time/day). | Dietary Supplement: 1 week placebo(Week 1)<br>* 1 week of consecutively consuming oral placebo (1 time/day)<br>Dietary Supplement: 1 week placebo(Week 2)<br>* 1 week of consecutively consuming oral placebo (1 time/day)<br>Dietary Supplement: 1 week placebo(Week 3)<br>* 1 week of consecutively consuming oral placebo (1 time/day)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The serum neutralizing antibody level of SARS-CoV-2. | The serum neutralizing antibody level of SARS-CoV-2 is determined by serum neutralization test, which is used to determine the serum dilution that protects 50% cells from cytopathic effect. | 12-24 weeks | 
| T-cell response level | Test of T-cell response level by spot-forming cell(SFC) counting, using Champspot III enzyme-linked spot automated image analysis system. | 12-24 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Antibody concentration | The binding antibody concentration of S protein IgG and IgA in SARS-CoV-2 serum. | 12-24 weeks | 
| PBMC transcriptome expression | The expression of PBMC transcriptome | 12-24 weeks | 
| Serum cytokines | The test of serum cytokines | 12-24 weeks | 
| Serum neutralizing antibody positive rate | The positive rate of serum neutralizing antibody. | 12-24 weeks | 
| Serum neutralizing antibody positive conversion rate | The positive conversion rate of serum neutralizing antibody. | 12-24 weeks | 
| Intestinal flora | The level of intestinal flora. | 12-24 weeks | 
| Fecal viable culture | The culture of fecal viable | 12-24 weeks | 
| Fecal specific binding antibody IgA | The specific binding antibody IgA of fecal | 12-24 weeks | 
| Blood pressure | The level of blood pressure. | 12-24 weeks | 
| Blood glucose | The level of blood glucose. | 12-24 weeks | 
| Blood lipid | The level of blood lipid. | 12-24 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Probiotic, lactobacillus plantarum