Safety and Efficacy of Lactobacillus plantarum K014 on Gastrointestinal and Immune Systems in Healthy Volunteers: A Randomized, Double-blind, Placebo-Controlled, Parallel-Group Trial
Probiotic K014 Clinical Trial (USM)
General Information
Lactobacillus plantarum has been extensively studied for its health benefits and versatility. It has a long history of safe use in food fermentation. Currently, it is employed in the probiotic field, with growing research on postbiotics derived from L. plantarum. Its efficacy in enhancing human health has been demonstrated in clinical trials. Recently, a new strain, L. plantarum K014, was isolated from fermented vegetables. As a newly identified strain, there is limited data on L. plantarum K014. Given the existing studies on L. plantarum, it would be interesting to investigate the potential effects and safety of L. plantarum K014 as a probiotic and postbiotic for gastrointestinal and immune health.
Despite the widespread use of L. plantarum as a probiotic and postbiotic globally, there is a lack of data on its effects and safety in Malaysia. Human trials are limited, especially for the new strain. Conducting a comprehensive human trial on L. plantarum in Malaysia is warranted to understand its potential benefits, considering the country's unique dietary and cultural factors.
2.0 Research questions
1. Would the administration of probiotic and postbiotic cause any adverse effects on gut health of healthy subjects?
2. Would the administration of probiotic and postbiotic cause any adverse effects on immune health of healthy subjects?
3. Does the intake of probiotic and postbiotic lead to better effectiveness in the enhancement of gut health of healthy subjects?
4. Does the intake of probiotic and postbiotic lead to better effectiveness in the enhancement of immune health of healthy subjects?
3.0 Objectives
3.1 General Objective:
To assess the safety of probiotic and postbiotic and evaluate their effectiveness in gut and immune health of healthy subjects.
3.2 Specific Objective:
3.2.1 Primary Objective:
a. To assess the safety of probiotic and postbiotic by observing the adverse effects on gut health of healthy subjects compare to placebo group.
b. To assess the safety of probiotic and postbiotic by observing the adverse effects on immune health of healthy subjects compare to placebo group.
3.2.2 Secondary Objective:
a. To evaluate the efficacy of probiotic and postbiotic on gut health of healthy subjects compare to placebo group.
b. To evaluate the efficacy of probiotic and postbiotic on immune health of healthy subjects compare to placebo group.
4.0 Study design
The study design will be single-centred, randomized, double-blind, placebo-controlled and parallel-group study for a duration of 26 weeks. This interventional study will involve the observation on the safety and effectiveness of the administration of probiotic and postbiotic from L. plantarum K014 in healthy subjects. There are three parallel arms in this study: probiotic, postbiotic, and placebo.
5.0 Study population & study site
The study will be implemented in the main campus of Universiti Sains Malaysia (USM), Pulau Penang. Participants involved are Malaysian healthy adults (students and staffs of USM) in good health without any diagnosed chronic diseases.
5.1 Inclusion Criteria
- Malaysian
- Adults age 18 years or more
- Adults in good health without any diagnosed chronic diseases
- Adults with no acute illnesses in the past 7 days
5.2 Exclusion Criteria
- Adults with history of consuming products containing probiotics or postbiotics one months prior to the study
- Adults who are allergic to probiotics, postbiotics, and maltodextrin
- Adult with gastrointestinal diseases, malnutrition, severe diseases and/or on long-term prescription medication
5.3 Sample size
A total of 300 participants will be included in this study. Each arm of the study consists of 100 subjects.
5.4 Study duration
The duration of the study is 6 months.
6.0 Trial interventions
6.1 Investigational Product (IP) Description
The investigational products of this study are probiotic, postbiotic (Ferment Lysate), and placebo. The probiotic contained active ingredient, ≥1×[10]^9 CFU of live L. plantarum K014 mixed with the excipient. While the postbiotic contained postbiotic which equivalent to ≥1×[10]^11 CFU of inanimate L. plantarum K014 and maltodextrin as excipient. The placebo contained only 2 gram of the excipient, maltodextrin. Each dose was supplied in an aluminium sachet.
6.2 Dosage and Administration
Probiotic: 1 sachet per day; Postbiotic: 1 sachet per day; Placebo: 1 sachet per day.
Participants are required to consume one sachet daily at a fixed dose of ≥1×[10]^11 CFU of L. plantarum K014 postbiotic and ≥1×[10]^9 CFU of L. plantarum K014 probiotic for a duration of 26 weeks.
6.3 Recruitment
Participants will be recruited by the co-researchers using random sampling method around the main campus of USM, Pulau Pinang. The recruitment information will be distributed through brochures, flyers and USM Pentadbir Emel to reach out the targeted participants. The brochures and flyers will be placed at several points of campus including the registration counter of Pusat Sejahtera, counter of main office of each school in the main campus.
6.4 Randomization
Randomisation of the eligible participants is carried out using an online randomisation software, named as GraphPad Software-QuickCalcs (http://graphpad.com/quickcals/randomize1/). They are randomised with a ratio of 1:1:1 into three arms of the study according to a computer generated, blocked randomisation list containing treatment codes.
6.5 Baseline Assessments
At baseline, participants’ demographic information will be collected. Subsequently, the anthropometric measurement and blood as well as urine test of the participants will be conducted and recorded by the medical officers in Pusat Sejahtera, USM. Questionnaires will be given to the participants for safety and efficacy assessments.
6.6 Subsequent Visits
Subsequent visits will occur at Month 1 (M1), 3 (M3), and 6 (M6) for safety and efficacy assessments for the duration of the study. There will be a total of 3 visits. At M1, anthropometric measurements and questionnaire of the participants will be collected and recorded by the medical officers in Pusat Sejahtera, USM. Following at M3 and M6, the anthropometric measurement and questionnaire of the participants are obtained, with concurrent blood and urine tests being conducted.
6.7 Safety Assessment
To assess safety, the following are observed:
i. Presence of gastrointestinal symptoms
ii. Presence of upper respiratory symptoms
iii. Presence of adverse effects
iv. Anthropometric measures which include body height, weight, body mass index (BMI), body fat composition, blood pressure, and heart rate.
v. Haematological measures which include full blood count.
vi. Biochemical measures which include sodium, potassium, chloride, urea, creatinine, calcium, phosphate, uric acid, EGFR, total protein, albumin, globulin, total bilirubin, ALP, AST (SGOT), ALT (SGPT), GGT, glucose, total cholesterol, HDL cholesterol, LDL cholesterol, triglycerides, total cholesterol/ HDL cholesterol, EFEME.
6.8 Efficacy Assessment
To assess efficacy, the following are observed:
i. Duration, episode, and frequency of the symptoms
ii. Severity of the symptoms
iii. Frequency and condition of defecation
Study Information
Inclusion & Exclusion Criteria
Study Timeline