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

NCT05195047 | Completed DMC

• 1 other identifier: GUANKE-Trial 2
• Study Type: interventional
• Target: 44
• Locations: 1 country
• Sites: 2

Brief Summary

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.

Conditions

SARS-CoV-2

Keywords

Probiotic; lactobacillus plantarum

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (11)

• Antibody concentration

  12-24 weeks

• PBMC transcriptome expression

  12-24 weeks

• Serum cytokines

  12-24 weeks

• Serum neutralizing antibody positive rate

  12-24 weeks

• Serum neutralizing antibody positive conversion rate

  12-24 weeks

Other Outcomes (1)

• Safety indicators

  12-24 weeks

Study Arms (4)

Probiotics-Placebo-Placebo

EXPERIMENTAL

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); Dietary Supplement: 1 week placebo(Week 2); Dietary Supplement: 1 week placebo(Week 3)

Placebo-Probiotics-Placebo

EXPERIMENTAL

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); Dietary Supplement: 1 week of probiotics(Week 2); Dietary Supplement: 1 week placebo(Week 3)

Placebo-Placebo-Probiotics

EXPERIMENTAL

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); Dietary Supplement: 1 week placebo(Week 2); Dietary Supplement: 1 week of probiotics(Week 3)

Placebo

PLACEBO COMPARATOR

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); Dietary Supplement: 1 week placebo(Week 2); Dietary Supplement: 1 week placebo(Week 3)

Interventions

1 week placebo(Week 1) DIETARY_SUPPLEMENT

1 week of consecutively consuming oral placebo (1 time/day)

Placebo; Placebo-Placebo-Probiotics; Placebo-Probiotics-Placebo

1 week of probiotics(Week 1) DIETARY_SUPPLEMENT

1 week of consecutively consuming oral probiotics (1 time/day)

Probiotics-Placebo-Placebo

1 week placebo(Week 2) DIETARY_SUPPLEMENT

1 week of consecutively consuming oral placebo (1 time/day)

Placebo; Placebo-Placebo-Probiotics; Probiotics-Placebo-Placebo

1 week of probiotics(Week 2) DIETARY_SUPPLEMENT

1 week of consecutively consuming oral probiotics (1 time/day)

Placebo-Probiotics-Placebo

1 week placebo(Week 3) DIETARY_SUPPLEMENT

1 week of consecutively consuming oral placebo (1 time/day)

Placebo; Placebo-Probiotics-Placebo; Probiotics-Placebo-Placebo

1 week of probiotics(Week 3) DIETARY_SUPPLEMENT

1 week of consecutively consuming oral probiotics (1 time/day)

Placebo-Placebo-Probiotics

Eligibility Criteria

• Age: 18 Years - 59 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• ≤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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Peking University: lead
• Centers for Disease Control and Prevention, China: collaborator
• Beijing Pinggu District Hospital: collaborator
• Peking University Health Science Center Hospital: collaborator

Study Sites (2)

Beijing Pinggu Hospital

Beijing, China

Location

Peking University Health Science Center Hospital

Beijing, China

Location

Related Publications (25)

• Shrotri M, Navaratnam AMD, Nguyen V, Byrne T, Geismar C, Fragaszy E, Beale S, Fong WLE, Patel P, Kovar J, Hayward AC, Aldridge RW; Virus Watch Collaborative. Spike-antibody waning after second dose of BNT162b2 or ChAdOx1. Lancet. 2021 Jul 31;398(10298):385-387. doi: 10.1016/S0140-6736(21)01642-1. Epub 2021 Jul 17. No abstract available.

  PMID: 34274038 BACKGROUND

• Naaber P, Tserel L, Kangro K, Sepp E, Jurjenson V, Adamson A, Haljasmagi L, Rumm AP, Maruste R, Karner J, Gerhold JM, Planken A, Ustav M, Kisand K, Peterson P. Dynamics of antibody response to BNT162b2 vaccine after six months: a longitudinal prospective study. Lancet Reg Health Eur. 2021 Nov;10:100208. doi: 10.1016/j.lanepe.2021.100208. Epub 2021 Sep 6.

  PMID: 34514454 BACKGROUND

• Liu YW, Liong MT, Tsai YC. New perspectives of Lactobacillus plantarum as a probiotic: The gut-heart-brain axis. J Microbiol. 2018 Sep;56(9):601-613. doi: 10.1007/s12275-018-8079-2. Epub 2018 Aug 23.

  PMID: 30141154 BACKGROUND

• Gorska A, Przystupski D, Niemczura MJ, Kulbacka J. Probiotic Bacteria: A Promising Tool in Cancer Prevention and Therapy. Curr Microbiol. 2019 Aug;76(8):939-949. doi: 10.1007/s00284-019-01679-8. Epub 2019 Apr 4.

  PMID: 30949803 BACKGROUND

• Huang Y, Wang X, Wang J, Wu F, Sui Y, Yang L, Wang Z. Lactobacillus plantarum strains as potential probiotic cultures with cholesterol-lowering activity. J Dairy Sci. 2013 May;96(5):2746-53. doi: 10.3168/jds.2012-6123. Epub 2013 Mar 15.

  PMID: 23498020 BACKGROUND

• Li J, Zhao F, Wang Y, Chen J, Tao J, Tian G, Wu S, Liu W, Cui Q, Geng B, Zhang W, Weldon R, Auguste K, Yang L, Liu X, Chen L, Yang X, Zhu B, Cai J. Gut microbiota dysbiosis contributes to the development of hypertension. Microbiome. 2017 Feb 1;5(1):14. doi: 10.1186/s40168-016-0222-x.

  PMID: 28143587 BACKGROUND

• Palmu J, Salosensaari A, Havulinna AS, Cheng S, Inouye M, Jain M, Salido RA, Sanders K, Brennan C, Humphrey GC, Sanders JG, Vartiainen E, Laatikainen T, Jousilahti P, Salomaa V, Knight R, Lahti L, Niiranen TJ. Association Between the Gut Microbiota and Blood Pressure in a Population Cohort of 6953 Individuals. J Am Heart Assoc. 2020 Aug 4;9(15):e016641. doi: 10.1161/JAHA.120.016641. Epub 2020 Jul 21.

  PMID: 32691653 BACKGROUND

• Khalesi S, Sun J, Buys N, Jayasinghe R. Effect of probiotics on blood pressure: a systematic review and meta-analysis of randomized, controlled trials. Hypertension. 2014 Oct;64(4):897-903. doi: 10.1161/HYPERTENSIONAHA.114.03469. Epub 2014 Jul 21.

  PMID: 25047574 BACKGROUND

• Wu Y, Zhang Q, Ren Y, Ruan Z. Effect of probiotic Lactobacillus on lipid profile: A systematic review and meta-analysis of randomized, controlled trials. PLoS One. 2017 Jun 8;12(6):e0178868. doi: 10.1371/journal.pone.0178868. eCollection 2017.

  PMID: 28594860 BACKGROUND

• Bock PM, Telo GH, Ramalho R, Sbaraini M, Leivas G, Martins AF, Schaan BD. The effect of probiotics, prebiotics or synbiotics on metabolic outcomes in individuals with diabetes: a systematic review and meta-analysis. Diabetologia. 2021 Jan;64(1):26-41. doi: 10.1007/s00125-020-05295-1. Epub 2020 Oct 13.

  PMID: 33047170 BACKGROUND

• Seddik HA, Bendali F, Gancel F, Fliss I, Spano G, Drider D. Lactobacillus plantarum and Its Probiotic and Food Potentialities. Probiotics Antimicrob Proteins. 2017 Jun;9(2):111-122. doi: 10.1007/s12602-017-9264-z.

  PMID: 28271469 BACKGROUND

• Kujawa-Szewieczek A, Adamczak M, Kwiecien K, Dudzicz S, Gazda M, Wiecek A. The Effect of Lactobacillus plantarum 299v on the Incidence of Clostridium difficile Infection in High Risk Patients Treated with Antibiotics. Nutrients. 2015 Dec 4;7(12):10179-88. doi: 10.3390/nu7125526.

  PMID: 26690209 BACKGROUND

• Ducrotte P, Sawant P, Jayanthi V. Clinical trial: Lactobacillus plantarum 299v (DSM 9843) improves symptoms of irritable bowel syndrome. World J Gastroenterol. 2012 Aug 14;18(30):4012-8. doi: 10.3748/wjg.v18.i30.4012.

  PMID: 22912552 BACKGROUND

• Fuentes MC, Lajo T, Carrion JM, Cune J. Cholesterol-lowering efficacy of Lactobacillus plantarum CECT 7527, 7528 and 7529 in hypercholesterolaemic adults. Br J Nutr. 2013 May 28;109(10):1866-72. doi: 10.1017/S000711451200373X. Epub 2012 Sep 28.

  PMID: 23017585 BACKGROUND

• Miele E, Pascarella F, Giannetti E, Quaglietta L, Baldassano RN, Staiano A. Effect of a probiotic preparation (VSL#3) on induction and maintenance of remission in children with ulcerative colitis. Am J Gastroenterol. 2009 Feb;104(2):437-43. doi: 10.1038/ajg.2008.118. Epub 2009 Jan 20.

  PMID: 19174792 BACKGROUND

• Szymanski H, Armanska M, Kowalska-Duplaga K, Szajewska H. Bifidobacterium longum PL03, Lactobacillus rhamnosus KL53A, and Lactobacillus plantarum PL02 in the prevention of antibiotic-associated diarrhea in children: a randomized controlled pilot trial. Digestion. 2008;78(1):13-7. doi: 10.1159/000151300. Epub 2008 Aug 14.

  PMID: 18701826 BACKGROUND

• Liu YW, Liong MT, Chung YE, Huang HY, Peng WS, Cheng YF, Lin YS, Wu YY, Tsai YC. Effects of Lactobacillus plantarum PS128 on Children with Autism Spectrum Disorder in Taiwan: A Randomized, Double-Blind, Placebo-Controlled Trial. Nutrients. 2019 Apr 11;11(4):820. doi: 10.3390/nu11040820.

  PMID: 30979038 BACKGROUND

• Hwang YH, Park S, Paik JW, Chae SW, Kim DH, Jeong DG, Ha E, Kim M, Hong G, Park SH, Jung SJ, Lee SM, Na KH, Kim J, Chung YC. Efficacy and Safety of Lactobacillus Plantarum C29-Fermented Soybean (DW2009) in Individuals with Mild Cognitive Impairment: A 12-Week, Multi-Center, Randomized, Double-Blind, Placebo-Controlled Clinical Trial. Nutrients. 2019 Feb 1;11(2):305. doi: 10.3390/nu11020305.

  PMID: 30717153 BACKGROUND

• Hakansson A, Andren Aronsson C, Brundin C, Oscarsson E, Molin G, Agardh D. Effects of Lactobacillus plantarum and Lactobacillus paracasei on the Peripheral Immune Response in Children with Celiac Disease Autoimmunity: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial. Nutrients. 2019 Aug 16;11(8):1925. doi: 10.3390/nu11081925.

  PMID: 31426299 BACKGROUND

• Chong HX, Yusoff NAA, Hor YY, Lew LC, Jaafar MH, Choi SB, Yusoff MSB, Wahid N, Abdullah MFIL, Zakaria N, Ong KL, Park YH, Liong MT. Lactobacillus plantarum DR7 alleviates stress and anxiety in adults: a randomised, double-blind, placebo-controlled study. Benef Microbes. 2019 Apr 19;10(4):355-373. doi: 10.3920/BM2018.0135. Epub 2019 Mar 18.

  PMID: 30882244 BACKGROUND

• Lee A, Lee YJ, Yoo HJ, Kim M, Chang Y, Lee DS, Lee JH. Consumption of Dairy Yogurt Containing Lactobacillus paracasei ssp. paracasei, Bifidobacterium animalis ssp. lactis and Heat-Treated Lactobacillus plantarum Improves Immune Function Including Natural Killer Cell Activity. Nutrients. 2017 May 31;9(6):558. doi: 10.3390/nu9060558.

  PMID: 28561762 BACKGROUND

• Lew LC, Hor YY, Yusoff NAA, Choi SB, Yusoff MSB, Roslan NS, Ahmad A, Mohammad JAM, Abdullah MFIL, Zakaria N, Wahid N, Sun Z, Kwok LY, Zhang H, Liong MT. Probiotic Lactobacillus plantarum P8 alleviated stress and anxiety while enhancing memory and cognition in stressed adults: A randomised, double-blind, placebo-controlled study. Clin Nutr. 2019 Oct;38(5):2053-2064. doi: 10.1016/j.clnu.2018.09.010. Epub 2018 Sep 19.

  PMID: 30266270 BACKGROUND

• Nam B, Kim SA, Park SD, Kim HJ, Kim JS, Bae CH, Kim JY, Nam W, Lee JL, Sim JH. Regulatory effects of Lactobacillus plantarum HY7714 on skin health by improving intestinal condition. PLoS One. 2020 Apr 10;15(4):e0231268. doi: 10.1371/journal.pone.0231268. eCollection 2020.

  PMID: 32275691 BACKGROUND

• Kageyama Y, Nishizaki Y, Aida K, Yayama K, Ebisui T, Akiyama T, Nakamura T. Lactobacillus plantarum induces innate cytokine responses that potentially provide a protective benefit against COVID-19: A single-arm, double-blind, prospective trial combined with an in vitro cytokine response assay. Exp Ther Med. 2022 Jan;23(1):20. doi: 10.3892/etm.2021.10942. Epub 2021 Nov 2.

  PMID: 34815772 BACKGROUND

• Lee MC, Tu YT, Lee CC, Tsai SC, Hsu HY, Tsai TY, Liu TH, Young SL, Lin JS, Huang CC. Lactobacillus plantarum TWK10 Improves Muscle Mass and Functional Performance in Frail Older Adults: A Randomized, Double-Blind Clinical Trial. Microorganisms. 2021 Jul 8;9(7):1466. doi: 10.3390/microorganisms9071466.

  PMID: 34361902 BACKGROUND

Study Officials

• Yangfeng Wu, PHD

  Peking University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: This study is double-blinded, which neither participants nor investigators know the results of intervention. In addition, laboratory test of blood samples will also be conducted without knowing the randomization results of participants to ensure the evaluation of outcome measure is objective.
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Epidemiology and Sciences in Clincial Research

Model Details: A prospective, randomized, double-blind, placebo parallel controlled clinical trial.

Study Record Dates

• First Submitted: January 12, 2022
• First Posted: January 18, 2022
• Study Start: February 27, 2022
• Primary Completion: August 21, 2022
• Study Completion: August 21, 2022
• Last Updated: November 3, 2022

Record last verified: 2022-11

Locations

CN (2)