UMIN-CTR Clinical Trial
| Unique ID issued by UMIN | UMIN000040479 |
|---|---|
| Receipt number | 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 08:47:41 |
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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
| Japan |
Condition
Condition
COVID-19
Classification by specialty
| Pneumology | Infectious disease | Adult |
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
| Food |
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
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
| 20 | years-old | <= |
Age-upper limit
| 70 | years-old | > |
Gender
Male and Female
Key inclusion criteria
Healthy volunteers
Key exclusion criteria
1) Current infectious, inflammatory, or immune-related diseases
2) Pregnant female
Target sample size
30
Research contact person
Name of lead principal investigator
| 1st name | Tsutomu |
| Middle name | |
| Last name | Nakamura |
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
| 1st name | Tomoka |
| Middle name | |
| Last name | Ebisui |
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 or person
Institute
Administration Department, Takanawa Clinic
Institute
Department
Personal name
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
| 2020 | Year | 05 | Month | 22 | Day |
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
| 2021 | Year | 09 | Month | 11 | Day |
Results Delayed
Results Delay Reason
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.
Plan to share IPD
IPD sharing Plan description
Progress
Recruitment status
Completed
Date of protocol fixation
| 2020 | Year | 04 | Month | 26 | Day |
Date of IRB
| 2020 | Year | 05 | Month | 07 | Day |
Anticipated trial start date
| 2020 | Year | 05 | Month | 22 | Day |
Last follow-up date
| 2020 | Year | 06 | Month | 30 | Day |
Date of closure to data entry
Date trial data considered complete
Date analysis concluded
Other
Other related information
Management information
Registered date
| 2020 | Year | 05 | Month | 21 | Day |
Last modified on
| 2021 | Year | 09 | Month | 11 | Day |
Link to view the page
Value
https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000046202
