<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT03268447</url>
  </required_header>
  <id_info>
    <org_study_id>USM/JEPeM/16050195</org_study_id>
    <nct_id>NCT03268447</nct_id>
  </id_info>
  <brief_title>Lactobacillus Plantarum P8 for Its Brain Health Promotion Potential</brief_title>
  <acronym>P8</acronym>
  <official_title>Lactobacillus Plantarum P8 for Its Brain Health Promotion Potential</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Universiti Sains Malaysia</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Beijing Scitop Bio-Tech Shareholding Co.Ltd.</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Universiti Sains Malaysia</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      This project aims to study the benefits of probiotics namely Lactobacillus plantarum P8 for&#xD;
      brain health properties, primarily alleviation of stress, among adults in Malaysia aged from&#xD;
      18 to 60 years.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The emerging concept of gut-brain-axis has been implying that gut health plays a pivotal role&#xD;
      in maintaining brain health4. Probiotics have entered the picture in promoting gut health for&#xD;
      better brain health. Probiotic can be defined as &quot;live microorganisms that grant health&#xD;
      effects to the host if consumed in sufficient amounts&quot;. Lactobacilli, as one of the largest&#xD;
      genera for probiotic microorganisms have been researched to alleviate stress, anxiety and/or&#xD;
      depression disorders.&#xD;
&#xD;
      L. plantarum P8 was isolated from traditionally fermented sour milk samples collected from&#xD;
      herdsmen in Wulatezhongqi grassland, Bayannaoer, Inner Mongolia, China. L. plantarum P8 was&#xD;
      selected as it was the best among 347 other Lactobacillus strains with excellent tolerance to&#xD;
      gastric acid, intestinal fluid and bile salt of the digestive system. P8 is incorporated and&#xD;
      sold in the market of China, Taiwan and Singapore in a variety of products, ranging from&#xD;
      dairy (yoghurt and fermented milk), health supplements to pet foods. P8 is patented in China&#xD;
      and also awarded by the Chinese government as a functional probiotic. Two human clinical&#xD;
      trials have shown that the administration of P8 at a concentration of 10 log CFU/day for&#xD;
      4-weeks, improved gastrointestinal health of adults subjects via increasing the population of&#xD;
      beneficial gut microbiota accompanied by decreasing gut opportunistic pathogens, increasing&#xD;
      fecal levels of secretory immunoglobulin-A and short chain fatty acids.&#xD;
&#xD;
      Thus, with evidence from other studies supporting the stress-alleviation effects of&#xD;
      lactobacilli and the current gut modulation properties of P8, we believe that L. plantarum P8&#xD;
      could exert stress alleviation potentials as well.&#xD;
&#xD;
      P8 has confirmed its safety for consumption, and for this intervention, it will be produced&#xD;
      under ISO9001 and HALAL in China. HALAL certification is provided by ARA HALAL Development&#xD;
      Services Center Inc. (ARA), which is recognized by JAKIM, Malaysia, an organization that&#xD;
      oversees the implementation of Halal requirement in Malaysia.&#xD;
&#xD;
      A total number of 176 healthy adults from age 18 -60 years old will be recruited for this&#xD;
      study.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">August 5, 2017</start_date>
  <completion_date type="Actual">January 31, 2018</completion_date>
  <primary_completion_date type="Actual">January 31, 2018</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <intervention_model_description>Placebo and P8 will be administered via a parallel design</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Triple (Participant, Care Provider, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Perceived Stress Scale (PSS) Scores</measure>
    <time_frame>12 weeks</time_frame>
    <description>Stress Questionnaires for the determination of stress (low, moderate, high)</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Fecal microbiota profiling</measure>
    <time_frame>12 weeks</time_frame>
    <description>Deoxyribonucleic acid (DNA) sequencing of fecal samples to compare DNA sequences of the different microbiota between adult participants taking P8 vs. placebo</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">120</enrollment>
  <condition>Healthy Volunteers</condition>
  <arm_group>
    <arm_group_label>Lactobacillus plantarum P8</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Intervention consists of daily administration of 2g probiotic Lactobacillus plantarum P8, administered daily at a fixed dosage of 10 log CFU/sachet/day and continue for 12 weeks.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Intervention consists of daily administration of 2g placebo (no probiotic bacteria), administered daily and continue for 12 weeks.</description>
  </arm_group>
  <intervention>
    <intervention_type>Dietary Supplement</intervention_type>
    <intervention_name>Lactobacillus plantarum P8</intervention_name>
    <description>This project aims to study the benefits of probiotics namely Lactobacillus plantarum P8 for brain health benefits primarily to alleviate stress, among adults in Malaysia aged from 18-60 years.</description>
    <arm_group_label>Lactobacillus plantarum P8</arm_group_label>
    <other_name>P8</other_name>
  </intervention>
  <intervention>
    <intervention_type>Dietary Supplement</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>This project aims to study the benefits of probiotics namely Lactobacillus plantarum P8 for brain health benefits primarily to alleviate stress, among adults in Malaysia aged from 18-60 years.</description>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Male or female subjects&#xD;
&#xD;
          -  18-60 years old&#xD;
&#xD;
          -  No severe illness&#xD;
&#xD;
          -  BMI within a healthy range&#xD;
&#xD;
          -  Score between 13 -20 (moderate stress level) on Cohen's Perceived Stress Scale (PSS)&#xD;
&#xD;
          -  Willing to commit throughout the experiment&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Type-1 diabetes (one of the main metabolite of Lactobacillus is acetic acid. Acetic&#xD;
             acid has been reported to affect lipid metabolism in the liver and fat digestion in&#xD;
             the pancreas in animal studies, and has been applied in obesity studies)&#xD;
&#xD;
          -  Long term medication due to certain severe illness (certain medications may interfere&#xD;
             with the survivability of Lactobacillus in the gut, for example the interactions&#xD;
             between probiotics and warfarin&#xD;
&#xD;
          -  HIV/AIDS (there has been no substantial data on the detrimental effects of probiotics&#xD;
             on AIDS patients. However, AIDS patient may be immune-compromised in the sense of&#xD;
             &quot;leaky gut&quot; that may lead to bacterial translocation, including translocation of&#xD;
             Lactobacillus outside the gut environment, into the blood stream)&#xD;
&#xD;
          -  Glucose-6-phosphate dehydrogenase (G6PD) deficiency (there has been no substantial&#xD;
             data on the detrimental effects of probiotics on G6PD deficiency people. However,&#xD;
             certain strains of probiotics have been reported to benefit RBC irregularity disorders&#xD;
             such as spur cells formation. One of the main mechanisms, involve the alteration of&#xD;
             RBC membrane. Although this is a benefit, we are unsure of the effects on G6PD&#xD;
             deficiency people, with weaker RBC).&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>60 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Min Tze Liong, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Universiti Sains Malaysia</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>School of Industrial Technology</name>
      <address>
        <city>Universiti Sains Malaysia</city>
        <state>Penang</state>
        <zip>11900</zip>
        <country>Malaysia</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Malaysia</country>
  </location_countries>
  <reference>
    <citation>Kwok LY, Guo Z, Zhang J, Wang L, Qiao J, Hou Q, Zheng Y, Zhang H. The impact of oral consumption of Lactobacillus plantarum P-8 on faecal bacteria revealed by pyrosequencing. Benef Microbes. 2015;6(4):405-13. doi: 10.3920/BM2014.0063. Epub 2015 Feb 12.</citation>
    <PMID>25653153</PMID>
  </reference>
  <reference>
    <citation>Wang L, Zhang J, Guo Z, Kwok L, Ma C, Zhang W, Lv Q, Huang W, Zhang H. Effect of oral consumption of probiotic Lactobacillus planatarum P-8 on fecal microbiota, SIgA, SCFAs, and TBAs of adults of different ages. Nutrition. 2014 Jul-Aug;30(7-8):776-83.e1. doi: 10.1016/j.nut.2013.11.018. Epub 2013 Dec 4.</citation>
    <PMID>24984992</PMID>
  </reference>
  <verification_date>July 2018</verification_date>
  <study_first_submitted>August 25, 2017</study_first_submitted>
  <study_first_submitted_qc>August 30, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">August 31, 2017</study_first_posted>
  <last_update_submitted>July 2, 2018</last_update_submitted>
  <last_update_submitted_qc>July 2, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">July 3, 2018</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Universiti Sains Malaysia</investigator_affiliation>
    <investigator_full_name>Min-Tze LIONG</investigator_full_name>
    <investigator_title>Professor Dr.</investigator_title>
  </responsible_party>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
    <ipd_description>General grouping data only</ipd_description>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03268447
org study id: USM/JEPeM/16050195
nct id: NCT03268447
lead sponsor: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
This project aims to study the benefits of probiotics namely Lactobacillus plantarum P8 for
      brain health properties, primarily alleviation of stress, among adults in Malaysia aged from
      18 to 60 years.
The emerging concept of gut-brain-axis has been implying that gut health plays a pivotal role
      in maintaining brain health4. Probiotics have entered the picture in promoting gut health for
      better brain health. Probiotic can be defined as "live microorganisms that grant health
      effects to the host if consumed in sufficient amounts". Lactobacilli, as one of the largest
      genera for probiotic microorganisms have been researched to alleviate stress, anxiety and/or
      depression disorders.

      L. plantarum P8 was isolated from traditionally fermented sour milk samples collected from
      herdsmen in Wulatezhongqi grassland, Bayannaoer, Inner Mongolia, China. L. plantarum P8 was
      selected as it was the best among 347 other Lactobacillus strains with excellent tolerance to
      gastric acid, intestinal fluid and bile salt of the digestive system. P8 is incorporated and
      sold in the market of China, Taiwan and Singapore in a variety of products, ranging from
      dairy (yoghurt and fermented milk), health supplements to pet foods. P8 is patented in China
      and also awarded by the Chinese government as a functional probiotic. Two human clinical
      trials have shown that the administration of P8 at a concentration of 10 log CFU/day for
      4-weeks, improved gastrointestinal health of adults subjects via increasing the population of
      beneficial gut microbiota accompanied by decreasing gut opportunistic pathogens, increasing
      fecal levels of secretory immunoglobulin-A and short chain fatty acids.

      Thus, with evidence from other studies supporting the stress-alleviation effects of
      lactobacilli and the current gut modulation properties of P8, we believe that L. plantarum P8
      could exert stress alleviation potentials as well.

      P8 has confirmed its safety for consumption, and for this intervention, it will be produced
      under ISO9001 and HALAL in China. HALAL certification is provided by ARA HALAL Development
      Services Center Inc. (ARA), which is recognized by JAKIM, Malaysia, an organization that
      oversees the implementation of Halal requirement in Malaysia.

      A total number of 176 healthy adults from age 18 -60 years old will be recruited for this
      study.
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: Placebo and P8 will be administered via a parallel design
primary purpose: Treatment
masking: Triple (Participant, Care Provider, Investigator)
measure: Perceived Stress Scale (PSS) Scores
time frame: 12 weeks
description: Stress Questionnaires for the determination of stress (low, moderate, high)
measure: Fecal microbiota profiling
time frame: 12 weeks
description: Deoxyribonucleic acid (DNA) sequencing of fecal samples to compare DNA sequences of the different microbiota between adult participants taking P8 vs. placebo
arm group label: Lactobacillus plantarum P8
arm group type: Active Comparator
description: Intervention consists of daily administration of 2g probiotic Lactobacillus plantarum P8, administered daily at a fixed dosage of 10 log CFU/sachet/day and continue for 12 weeks.
arm group label: Placebo
arm group type: Placebo Comparator
description: Intervention consists of daily administration of 2g placebo (no probiotic bacteria), administered daily and continue for 12 weeks.
intervention type: Dietary Supplement
intervention name: Lactobacillus plantarum P8
description: This project aims to study the benefits of probiotics namely Lactobacillus plantarum P8 for brain health benefits primarily to alleviate stress, among adults in Malaysia aged from 18-60 years.
arm group label: Lactobacillus plantarum P8
other name: P8
intervention type: Dietary Supplement
intervention name: Placebo
description: This project aims to study the benefits of probiotics namely Lactobacillus plantarum P8 for brain health benefits primarily to alleviate stress, among adults in Malaysia aged from 18-60 years.
arm group label: Placebo
criteria: 
gender: All
minimum age: 18 Years
maximum age: 60 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Min Tze Liong, PhD
role: Principal Investigator
affiliation: Universiti Sains Malaysia
facility: 
country: Malaysia
citation: Kwok LY, Guo Z, Zhang J, Wang L, Qiao J, Hou Q, Zheng Y, Zhang H. The impact of oral consumption of Lactobacillus plantarum P-8 on faecal bacteria revealed by pyrosequencing. Benef Microbes. 2015;6(4):405-13. doi: 10.3920/BM2014.0063. Epub 2015 Feb 12.
PMID: 25653153
citation: Wang L, Zhang J, Guo Z, Kwok L, Ma C, Zhang W, Lv Q, Huang W, Zhang H. Effect of oral consumption of probiotic Lactobacillus planatarum P-8 on fecal microbiota, SIgA, SCFAs, and TBAs of adults of different ages. Nutrition. 2014 Jul-Aug;30(7-8):776-83.e1. doi: 10.1016/j.nut.2013.11.018. Epub 2013 Dec 4.
PMID: 24984992
responsible party type: Principal Investigator
investigator affiliation: Universiti Sains Malaysia
investigator full name: Min-Tze LIONG
investigator title: Professor Dr.
sharing ipd: No
ipd description: General grouping data only