<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/NCT03292978</url>
  </required_header>
  <id_info>
    <org_study_id>DIC2016-08</org_study_id>
    <nct_id>NCT03292978</nct_id>
  </id_info>
  <brief_title>An Intervention on Healthy Adults of Probiotics on Gut Flora Metabolisms of Choline</brief_title>
  <official_title>Probiotics Intervention on Gut Flora Metabolisms of Choline:A Randomized Double-Blind Control Trial</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Huilian Zhu</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Sun Yat-sen University</source>
  <oversight_info>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      The aim of the study is to examine the effects of probiotics intervention on choline&#xD;
      metabolites and intestinal microbiota composition using a randomized double blind clinical&#xD;
      trial. Also, we proposed to explore the real-time change of choline metabolites after&#xD;
      probiotics intervention through a PC challenge test. Our study will clarify the biochemical&#xD;
      pathway involved in metabolic diseases and hope to provide a new targeted-preventive and&#xD;
      therapeutic strategy for chronic metabolic diseases.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Dietary choline (mainly refer to phosphatidylcholine, PC) produce trimethylamine (TMA)&#xD;
      through the action of gut flora in vivo. TMA then readily absorbed into systemic circulation&#xD;
      and oxidized by hepatic flavin monoxygenases (FMO3) to trimethylamine-N-oxide (TMAO). The&#xD;
      elevated levels of circulating TMAO is identified as a risk factor for the prevalence and&#xD;
      development of metabolic diseases such as cardiovascular diseases and nonalcoholic fatty&#xD;
      liver diseases. Targeting gut flora for reducing TMAO may be a promising approach for&#xD;
      preventing chronic metabolic diseases. Recent studies found that some strains representing&#xD;
      two different phyla (Firmicutes and Proteobacteria) are capable of producing TMA from choline&#xD;
      in vitro. On the other hand, TMA intervention can change the structure of intestinal flora,&#xD;
      reducing the abundance of bifidobacterium and lactobacillus. Probiotics can improve the&#xD;
      ecological balance of the gut flora, which might be beneficial to human health and disease&#xD;
      prevention. However, whether probiotics could inhibit the TMA-producing bacterias and reduce&#xD;
      the TMA and TMAO levels through balancing the gut flora was unclear.&#xD;
&#xD;
      In order to explore whether probiotics can reduce the TMA and TMAO levels, we are proposed to&#xD;
      recruit 50 volunteers aged from 18-30 years old to participate in the randomized double-blind&#xD;
      trial. The volunteers are randomized allocated into different intervention groups. The&#xD;
      probiotics intervention group is provided once daily orally-taken powder in a sachet, which&#xD;
      contains 4 strains of probiotics. The non-probiotic control is provided with a powder without&#xD;
      probiotics , but has same look, color, taste, flavor and weight as the probiotics&#xD;
      intervention group. A PC challenge test will be hold before and after the 4 weeks&#xD;
      intervention. The blood and fecal sample will be collected before and after the trial and&#xD;
      analyzed by appropriate method. The dietary assessment is assessed by a 3-day dietary&#xD;
      record.The statistic analysis is by SPSS 23.0.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">July 1, 2017</start_date>
  <completion_date type="Actual">December 31, 2018</completion_date>
  <primary_completion_date type="Actual">December 31, 2017</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>
    <primary_purpose>Basic Science</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>choline metabolites</measure>
    <time_frame>4 weeks later</time_frame>
    <description>The metabolites of choline before and after the intervention including free choline, betaine, TMA, TMAO will be measured by UPLC/MS.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>intestinal microbiota composition</measure>
    <time_frame>4 weeks later</time_frame>
    <description>The intestinal microbiota composition of feces before and after the intervention will be examined by 16S-DNA.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>anthropometry measurement</measure>
    <time_frame>4 weeks later</time_frame>
    <description>The height and weight which are combined to report BMI in kg/m^2 will be measured before and after the intervention by professional investigators.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>blood biochemical markers</measure>
    <time_frame>4 weeks later</time_frame>
    <description>Overnight fasting serum total cholesterol (TC), triglyceride (TG), LDL cholesterol (LDLc), HDL cholesterol (HDLc) and fasting blood glucose were measured by colorimetric methods using a Hitachi 7600-010 automated analyzer.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">40</enrollment>
  <condition>Healthy</condition>
  <arm_group>
    <arm_group_label>probiotics intervention</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>The probiotic is provided in sachets as a 2g powder dried with corn starch.&#xD;
The powder is orally taken once daily for 4 weeks.&#xD;
The powder contains totally 11 log 10 colony forming units(CFU) of probiotics.&#xD;
The types of probiotics are Lactobacillus.rhamnosus, Lactobacillus.acidophilus, Bifidobacteria.animalis and Bifidobacteria.longum.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>non-probiotic control</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>The placebo is corn starch alone provided and the shape, color, weight,flavor and taste are same with the powder of probiotics intervention.</description>
  </arm_group>
  <intervention>
    <intervention_type>Dietary Supplement</intervention_type>
    <intervention_name>probiotics intervention</intervention_name>
    <description>The probiotics intention is provided with 4 strains of probiotics as a 2g sachet powder, dried with corn starch for 4 weeks.</description>
    <arm_group_label>probiotics intervention</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Dietary Supplement</intervention_type>
    <intervention_name>non-probiotic control</intervention_name>
    <description>The placebo is corn starch alone provided and the shape, color, flavor and taste are same with the powder of probiotics intervention.</description>
    <arm_group_label>non-probiotic control</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Healthy males at 18 to 30 years old;&#xD;
&#xD;
          -  Free from antibiotics and probiotic products for at least 1 month;&#xD;
&#xD;
          -  Willing to participate in the study, consume the test product and perform all&#xD;
             measurements.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Sever physical diseases;&#xD;
&#xD;
          -  Intolerance to probiotics or eggs&#xD;
      </textblock>
    </criteria>
    <gender>Male</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>30 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Zhu Hui lian, Professor</last_name>
    <role>Study Chair</role>
    <affiliation>Sun Yat-sen University</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>SunYat-sen University</name>
      <address>
        <city>Guangzhou</city>
        <state>Guangdong</state>
        <zip>510080</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <verification_date>November 2019</verification_date>
  <study_first_submitted>September 19, 2017</study_first_submitted>
  <study_first_submitted_qc>September 22, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">September 26, 2017</study_first_posted>
  <last_update_submitted>November 11, 2019</last_update_submitted>
  <last_update_submitted_qc>November 11, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">November 13, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor-Investigator</responsible_party_type>
    <investigator_affiliation>Sun Yat-sen University</investigator_affiliation>
    <investigator_full_name>Huilian Zhu</investigator_full_name>
    <investigator_title>Professor</investigator_title>
  </responsible_party>
  <!-- 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/NCT03292978
org study id: DIC2016-08
nct id: NCT03292978
lead sponsor: 
is fda regulated drug: No
is fda regulated device: No
The aim of the study is to examine the effects of probiotics intervention on choline
      metabolites and intestinal microbiota composition using a randomized double blind clinical
      trial. Also, we proposed to explore the real-time change of choline metabolites after
      probiotics intervention through a PC challenge test. Our study will clarify the biochemical
      pathway involved in metabolic diseases and hope to provide a new targeted-preventive and
      therapeutic strategy for chronic metabolic diseases.
Dietary choline (mainly refer to phosphatidylcholine, PC) produce trimethylamine (TMA)
      through the action of gut flora in vivo. TMA then readily absorbed into systemic circulation
      and oxidized by hepatic flavin monoxygenases (FMO3) to trimethylamine-N-oxide (TMAO). The
      elevated levels of circulating TMAO is identified as a risk factor for the prevalence and
      development of metabolic diseases such as cardiovascular diseases and nonalcoholic fatty
      liver diseases. Targeting gut flora for reducing TMAO may be a promising approach for
      preventing chronic metabolic diseases. Recent studies found that some strains representing
      two different phyla (Firmicutes and Proteobacteria) are capable of producing TMA from choline
      in vitro. On the other hand, TMA intervention can change the structure of intestinal flora,
      reducing the abundance of bifidobacterium and lactobacillus. Probiotics can improve the
      ecological balance of the gut flora, which might be beneficial to human health and disease
      prevention. However, whether probiotics could inhibit the TMA-producing bacterias and reduce
      the TMA and TMAO levels through balancing the gut flora was unclear.

      In order to explore whether probiotics can reduce the TMA and TMAO levels, we are proposed to
      recruit 50 volunteers aged from 18-30 years old to participate in the randomized double-blind
      trial. The volunteers are randomized allocated into different intervention groups. The
      probiotics intervention group is provided once daily orally-taken powder in a sachet, which
      contains 4 strains of probiotics. The non-probiotic control is provided with a powder without
      probiotics , but has same look, color, taste, flavor and weight as the probiotics
      intervention group. A PC challenge test will be hold before and after the 4 weeks
      intervention. The blood and fecal sample will be collected before and after the trial and
      analyzed by appropriate method. The dietary assessment is assessed by a 3-day dietary
      record.The statistic analysis is by SPSS 23.0.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Basic Science
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: choline metabolites
time frame: 4 weeks later
description: The metabolites of choline before and after the intervention including free choline, betaine, TMA, TMAO will be measured by UPLC/MS.
measure: intestinal microbiota composition
time frame: 4 weeks later
description: The intestinal microbiota composition of feces before and after the intervention will be examined by 16S-DNA.
measure: anthropometry measurement
time frame: 4 weeks later
description: The height and weight which are combined to report BMI in kg/m^2 will be measured before and after the intervention by professional investigators.
measure: blood biochemical markers
time frame: 4 weeks later
description: Overnight fasting serum total cholesterol (TC), triglyceride (TG), LDL cholesterol (LDLc), HDL cholesterol (HDLc) and fasting blood glucose were measured by colorimetric methods using a Hitachi 7600-010 automated analyzer.
arm group label: probiotics intervention
arm group type: Experimental
description: The probiotic is provided in sachets as a 2g powder dried with corn starch.
The powder is orally taken once daily for 4 weeks.
The powder contains totally 11 log 10 colony forming units(CFU) of probiotics.
The types of probiotics are Lactobacillus.rhamnosus, Lactobacillus.acidophilus, Bifidobacteria.animalis and Bifidobacteria.longum.
arm group label: non-probiotic control
arm group type: Placebo Comparator
description: The placebo is corn starch alone provided and the shape, color, weight,flavor and taste are same with the powder of probiotics intervention.
intervention type: Dietary Supplement
intervention name: probiotics intervention
description: The probiotics intention is provided with 4 strains of probiotics as a 2g sachet powder, dried with corn starch for 4 weeks.
arm group label: probiotics intervention
intervention type: Dietary Supplement
intervention name: non-probiotic control
description: The placebo is corn starch alone provided and the shape, color, flavor and taste are same with the powder of probiotics intervention.
arm group label: non-probiotic control
criteria: 
gender: Male
minimum age: 18 Years
maximum age: 30 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Zhu Hui lian, Professor
role: Study Chair
affiliation: Sun Yat-sen University
facility: 
country: China
responsible party type: Sponsor-Investigator
investigator affiliation: Sun Yat-sen University
investigator full name: Huilian Zhu
investigator title: Professor