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UMIN-CTR Clinical Trial |
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Name | UMIN ID |
Recruitment status | Completed |
Unique ID issued by UMIN | UMIN000040479 |
Receipt No. | R000046202 |
Scientific Title | Immunological efficacy of lactic acid bacteria for COVID-19: an open-label trial |
Date of disclosure of the study information | 2020/05/22 |
Last modified on | 2021/09/11 |
Basic information | ||
Public title | Immunological efficacy of lactic acid bacteria for COVID-19 | |
Acronym | COVID-19/lactic acid bacteria | |
Scientific Title | Immunological efficacy of lactic acid bacteria for COVID-19: an open-label trial | |
Scientific Title:Acronym | COVID-19/lactic acid bacteria | |
Region |
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Condition | ||||
Condition | COVID-19 | |||
Classification by specialty |
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Classification by malignancy | Others | |||
Genomic information | NO |
Objectives | |
Narrative objectives1 | A rapid increase in the numbers of patients with and deaths from COVID-19 is becoming a global threat to public health. One of the reasons for the current pandemic is that effective vaccine or specific drugs against COVID-19 remain unavailable. Previous studies have shown that intake of lactic acid bacteria has a preventive effect on the infection of influenza virus. However, the feasibility of prophylactic use against COVID-19 has not been confirmed. We thus examine whether hematological and immunological measures of healthy individuals are affected by the administration of lactic acid bacteria. |
Basic objectives2 | Efficacy |
Basic objectives -Others | |
Trial characteristics_1 | |
Trial characteristics_2 | |
Developmental phase |
Assessment | |
Primary outcomes | Plasma cytokine levels after the administration of lactic acid bacteria for 7 days . |
Key secondary outcomes | Hematology and blood biochemistry after the administration of lactic acid bacteria for 7 days . |
Base | |
Study type | Interventional |
Study design | |
Basic design | Single arm |
Randomization | Non-randomized |
Randomization unit | |
Blinding | Open -no one is blinded |
Control | Uncontrolled |
Stratification | |
Dynamic allocation | |
Institution consideration | |
Blocking | |
Concealment |
Intervention | ||
No. of arms | 1 | |
Purpose of intervention | Prevention | |
Type of intervention |
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Interventions/Control_1 | Using the lactic acid bacteria suitability assay, the best- and worst-matched species are selected for each subject from the following three species of lactic acid bacteria: Lactobacillus plantarum, Bifidobacterium longum, and Lactococcus lactis ssp. lactis, which have been shown to be effective for the prevention of influenza in previous studies. The subjects are instructed to take the species (granular powder) in accordance with the following protocol.
Duration: 3 weeks (the best-matched species for 1 week, washout for 1 week, and the worst-matched species for 1 week) Dose: one-hundred billion (heat-killed bacteria)/day Frequency: twice daily, morning and night at 12-hour intervals Blood sampling: 3 times |
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Interventions/Control_2 | ||
Interventions/Control_3 | ||
Interventions/Control_4 | ||
Interventions/Control_5 | ||
Interventions/Control_6 | ||
Interventions/Control_7 | ||
Interventions/Control_8 | ||
Interventions/Control_9 | ||
Interventions/Control_10 |
Eligibility | ||||
Age-lower limit |
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Age-upper limit |
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Gender | Male and Female | |||
Key inclusion criteria | Healthy volunteers | |||
Key exclusion criteria | 1) Current infectious, inflammatory, or immune-related diseases
2) Pregnant female |
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Target sample size | 30 |
Research contact person | |||||||
Name of lead principal investigator |
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Organization | Institute for Quantitative Biosciences, The University of Tokyo | ||||||
Division name | Laboratory of Molecular and Genetic Information | ||||||
Zip code | 113-0032 | ||||||
Address | 1-1-1, Yayoi, Bunkyo-ku, Tokyo | ||||||
TEL | 03-5841-7834 | ||||||
nakamurachibiko@gmail.com |
Public contact | |||||||
Name of contact person |
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Organization | Takanawa Clinic | ||||||
Division name | Administration Department | ||||||
Zip code | 140-0001 | ||||||
Address | 1-22-17, Kitashinagawa, Shinagawa-ku, Tokyo | ||||||
TEL | 03-6433-3165 | ||||||
Homepage URL | |||||||
jimukyoku@takanawa-clinic.com |
Sponsor | |
Institute | Administration Department, Takanawa Clinic |
Institute | |
Department |
Funding Source | |
Organization | Administration Department, Takanawa Clinic |
Organization | |
Division | |
Category of Funding Organization | Self funding |
Nationality of Funding Organization |
Other related organizations | |
Co-sponsor | |
Name of secondary funder(s) |
IRB Contact (For public release) | |
Organization | Research Ethics Committee of Takanawa Clinic |
Address | 1-22-17, Kitashinagawa, Shinagawa-ku, Tokyo |
Tel | 03-6712-9747 |
support@idou-medical.jp |
Secondary IDs | |
Secondary IDs | NO |
Study ID_1 | |
Org. issuing International ID_1 | |
Study ID_2 | |
Org. issuing International ID_2 | |
IND to MHLW |
Institutions | |
Institutions | 高輪クリニック(東京都) |
Other administrative information | |||||||
Date of disclosure of the study information |
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Related information | |
URL releasing protocol | Our protocol will be opened to the public in a scientific paper. |
Publication of results | Unpublished |
Result | |||||||
URL related to results and publications | Our findings will be opened to the public in a scientific paper. | ||||||
Number of participants that the trial has enrolled | 20 | ||||||
Results | L. plantarum showed the strikingly high innate cytokine index in all subjects in the in vitro cytokine response assay. In the subsequent trial, oral L. plantarum significantly increased the innate cytokine index and decreased the plasma level of IL-6. The cytokine index increased in 16 of 18 subjects with considerable individual differences in the fold change. In line with these innate cytokine changes, L. plantarum ingestion significantly enhanced the activity of natural killer cells. | ||||||
Results date posted |
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Results Delayed | |||||||
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Date of the first journal publication of results | |||||||
Baseline Characteristics | 18 healthy adult subjects (1 male, 17 females; ages 28-66 years; mean age [SD], 44.2 [10.1] years) completed the intervention. They had no recorded and reported comorbidities and were negative for PCR and IgM/IgG antibodies tests for SARS-CoV-2 at study entry (i.e. no previous and current SARS-CoV-2 infection). | ||||||
Participant flow | A total of 20 volunteers were screened for eligibility, found to be eligible, and enrolled in this trial. LAB species were administered to all the enrolled participants, 2 of whom were excluded from the main analysis due to no visit to our clinic after the LAB prescription. Consequently, 18 subjects completed the intervention, and the data were subjected to the statistical analysis. | ||||||
Adverse events | No adverse events were observed during this study period. | ||||||
Outcome measures | The primary outcome measure
Oral intake of L. plantarum significantly increased plasma IL-1beta (median [IQR]: 0.00 [0.00-0.00] vs 0.134 [0.0915-0.292] pg/mL; P = 0.0000310 in the Friedman test; P = 0.00284 in the post hoc Nemenyi test) and decreased plasma IL-6 (median [IQR]: 1.18 [0.812-2.13] vs 0.495 [0.425-0.775] pg/mL; P = 0.0131 in the Friedman test; P = 0.0128 in the post hoc Nemenyi test). There were no significant differences in the plasma levels of TNF-alpha, IL-18, and IL-8. Consequently, the QICI value was significantly increased (mean fold change: 16.8-fold; median [IQR]: 1760 [680-3550] vs 12300 [5440-42200]; P = 0.0173 in the Friedman test; P = 0.0138 in the post hoc Nemenyi test). The QICI values were increased in 16 of 18 subjects (88.9%) with considerable individual differences in the fold change (1.06-128-fold, mean fold change: 18.8-fold), suggesting that there are large variations in responsiveness to L. plantarum among individuals. In contrast, oral intake of B. longum induced a significant decrease in plasma IL-1beta (median [IQR]: 0.134 [0.0915-0.292] vs 0.00 [0.00-0.00] pg/mL; P = 0.0000310 in the Friedman test; P = 0.000706 in the post hoc Nemenyi test); however, the QICI value did not change significantly (mean fold change: 1.54-fold; median [IQR]: 12300 [5440-42200] vs 2780 [940-9820]; P = 0.0173 in the Friedman test; P = 0.474 in the post hoc Nemenyi test). The QICI values increased in 8 of 18 subjects (44.4%), but the fold changes were markedly lower (1.20-8.58-fold, mean fold change: 3.30-fold) than those obtained during the L. plantarum session. The secondary outcome measure We found that L. plantarum ingestion caused a minor but significant change in mean corpuscular hemoglobin concentration (median [IQR]: 33.3 [32.4-33.9] vs 32.6 [32.1-33.1] %; P = 0.00456 in the Friedman test; P = 0.00836 in the post hoc Nemenyi test). No significant changes in the hematological parameters were observed during the B. longum session. |
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Recruitment status | Completed | ||||||
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Last modified on |
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Link to view the page | |
URL(English) | https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000046202 |
Research Plan | |
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Research case data specifications | |
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Research case data | |
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