<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/NCT03259971</url>
  </required_header>
  <id_info>
    <org_study_id>201703061MIPA</org_study_id>
    <nct_id>NCT03259971</nct_id>
  </id_info>
  <brief_title>The Role of Probiotics PS128 in Movement Disorders</brief_title>
  <official_title>The Role of Probiotics PS128 in Movement Disorders</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>National Taiwan University Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>National Taiwan University Hospital</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>
      Pediatric movement disorders comprise of a large number of different neurological diseases&#xD;
      including Rett syndrome (RTT) and Tourette syndrome. Studies in the literature as well as our&#xD;
      preliminary reports showed that Rett syndrome and Tourette syndrome/Tic disorders are&#xD;
      associated with a dysbiosis of the gut microbiota compared to normal control. Probiotic&#xD;
      Lactobacillus plantarum PS128 is a diet supplement that available for human consumption.&#xD;
      Probiotic Lactobacillus plantarum PS128 had showed psychotropic effects such as ameliorate&#xD;
      anxiety- and depression-like behaviors as well as altered the level of neurotransmitters such&#xD;
      as dopamine in the brain in animal models, which might be through microbiota-gut-brain axis.&#xD;
      Therefore, the purpose of this study is to access the possible neurobehavior effects of&#xD;
      Probiotic Lactobacillus plantarum PS128 in Rett syndrome and Tic disorders/Tourette syndrome.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The study is a placebo-controlled double-blind randomized study, to determine the benefits of&#xD;
      probiotic Lactobacillus plantarum PS128 vs placebo on symptoms for Tic disorders; and the&#xD;
      symptoms, behavior, or cognition for Rett syndrome.&#xD;
&#xD;
      Patients with the Rett syndrome and Tic disorders/Tourette syndrome will be recruited into&#xD;
      our study.The study period will last 4 months for Rett syndrome patients, age one&#xD;
      year-50years; while 2 months for Tic disorders/Tourette syndrome patient, age 5 years-18&#xD;
      years.&#xD;
&#xD;
      The study will be performed in National Taiwan University Children Hospital. The patients&#xD;
      will have neuropsychological and gut microbiota evaluation before and at the end of the&#xD;
      study. There will also be interim follow up evaluations each month after the patient start&#xD;
      taking the probiotic or placebo.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date type="Actual">August 25, 2017</start_date>
  <completion_date type="Anticipated">August 20, 2021</completion_date>
  <primary_completion_date type="Anticipated">August 20, 2021</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>Treatment</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
    <masking_description>Randomized double blind placebo-controlled</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Neuropsychological test (Mullen Scales of Early Learning)</measure>
    <time_frame>Change at four months from baseline</time_frame>
    <description>for Rett syndrome</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Yale Global Tic Severity Scale (YGTSS)</measure>
    <time_frame>Change at 2 months from baseline</time_frame>
    <description>for Tic disorders</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>RTT severity score</measure>
    <time_frame>Change at four months from baseline</time_frame>
    <description>For Rett syndrome</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Dystonia status (Fahn Marsden rating scale/Unified Dystonia Rating Scale )</measure>
    <time_frame>Visit 1, Visit 2, Visit 3, Visit 4 (Up to 4 months)</time_frame>
    <description>For Rett syndrome</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Anxiety, Depression, and Mood Scale (ADAMS)</measure>
    <time_frame>Change at four months from baseline</time_frame>
    <description>For Rett syndrome</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Ghuman-Folstein Screen for Social Interaction (SSI)</measure>
    <time_frame>Change at four months from baseline</time_frame>
    <description>For Rett syndrome</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Vineland Adaptive Behavioral scale</measure>
    <time_frame>Change at four months from baseline</time_frame>
    <description>For Rett syndrome</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Early social communication scales</measure>
    <time_frame>Change at four months from baseline</time_frame>
    <description>For Rett syndrome</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pediatric Evaluation of Disability Inventory</measure>
    <time_frame>Change at four months from baseline</time_frame>
    <description>For Rett syndrome</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Stool and gut microbiota evaluation</measure>
    <time_frame>Change at four months from baseline</time_frame>
    <description>For Rett and Tic disorders</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Child Behavior Checklist (CBCL)</measure>
    <time_frame>Change at 2 months from baseline</time_frame>
    <description>For Tic disorders</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Continuous performance test</measure>
    <time_frame>Change at 2 months from baseline</time_frame>
    <description>For Tic disorders</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The Migraine Disability Assessment Test</measure>
    <time_frame>Change at 2 months from baseline</time_frame>
    <description>For Tic disorders</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Children's Depression Inventory</measure>
    <time_frame>Change at 2 months from baseline</time_frame>
    <description>For Tic disorders</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Obsessive-compulsive inventory</measure>
    <time_frame>Change at 2 months from baseline</time_frame>
    <description>For Tic disorders</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Swanson, Nolan and Pehlam version IV</measure>
    <time_frame>Change at 2 months from baseline</time_frame>
    <description>For Tic disorders</description>
  </secondary_outcome>
  <number_of_arms>4</number_of_arms>
  <enrollment type="Anticipated">500</enrollment>
  <condition>Rett Syndrome</condition>
  <condition>Tourette Syndrome</condition>
  <condition>Tic Disorders</condition>
  <arm_group>
    <arm_group_label>Placebo (for tic disorder)</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>The placebo will be dispensed to equal the volume of 1 tablet of Probiotic PS128, which is taken orally in 2 divided doses, 12 hours apart during the study period of 2 months for Tic disorders.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>PS128 (tic disorder)</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>The Probiotic group in tic disorder will take Probiotic-Lactobacillus plantarum PS128, which contain 300mg (3x10^10 CFU) Lactobacillus plantarum PS128 and 100mg of Microcrystalline Cellulose in each tablet. It will be taken orally in 2 divided doses, 12 hours apart during the study period of 2 months for Tic disorders.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo (for Rett syndrome)</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>The placebo will be dispensed to equal the volume of 1 tablet of Probiotic PS128, which is taken orally in 2 divided doses, 12 hours apart during the study period of 4 months for Rett syndrome</description>
  </arm_group>
  <arm_group>
    <arm_group_label>PS128 (Rett syndrome)</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>The Probiotic group will take Probiotic-Lactobacillus plantarum PS128, which contain 300mg (3x10^10 CFU) Lactobacillus plantarum PS128 and 100mg of Microcrystalline Cellulose in each tablet. It will be taken orally in 2 divided doses, 12 hours apart during the study period of 4 months for Rett Syndrome.</description>
  </arm_group>
  <intervention>
    <intervention_type>Dietary Supplement</intervention_type>
    <intervention_name>Probiotic-Lactobacillus plantarum PS128</intervention_name>
    <description>Probiotic supplement of Lactobacillus plantarum PS128 , 1 tablet , twice a day , 12 hrs apart, lasting 2 months for Tic disorders and 4 months for Rett syndrome</description>
    <arm_group_label>PS128 (Rett syndrome)</arm_group_label>
    <arm_group_label>PS128 (tic disorder)</arm_group_label>
    <other_name>Lactobacillus plantarum PS128</other_name>
  </intervention>
  <intervention>
    <intervention_type>Dietary Supplement</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>placebo , 1 tablet , twice a day , 12 hrs apart, lasting 2 months for Tic disorders and 4 months for Rett syndrome</description>
    <arm_group_label>Placebo (for Rett syndrome)</arm_group_label>
    <arm_group_label>Placebo (for tic disorder)</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Rett syndrome:&#xD;
&#xD;
          -  Males and females who have classic or atypical RTT diagnosed under consensus criteria&#xD;
&#xD;
          -  Age: 1-50 years&#xD;
&#xD;
          -  Tic disorders:&#xD;
&#xD;
          -  males and females with clinical diagnosis&#xD;
&#xD;
          -  Age: 8-18years&#xD;
&#xD;
          -  Treatment naive 4 weeks prior to study&#xD;
&#xD;
          -  Those with standard medications, dosage stable 4 weeks prior to study&#xD;
&#xD;
          -  AADC syndrome:&#xD;
&#xD;
          -  Males and females with AADC diagnosis&#xD;
&#xD;
          -  Age: 1-50 years&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Those who took probiotic or probiotic related product 4 weeks prior to the study or&#xD;
             during the study&#xD;
&#xD;
          -  Those who took antibiotic 4 weeks prior to the study&#xD;
&#xD;
          -  Those showing poor compliance with any aspect of the study&#xD;
&#xD;
          -  Those had adverse reactions to PS128&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>1 Year</minimum_age>
    <maximum_age>50 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Wang-Tso Lee, MD,PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>National Taiwan University Children Hospital</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Wang-Tso Lee, MD,PhD</last_name>
    <phone>+886-223123456</phone>
    <phone_ext>71618</phone_ext>
    <email>leeped@hotmail.com</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Lee Chin Wong, MD</last_name>
    <phone>+886-223123456</phone>
    <phone_ext>71618</phone_ext>
    <email>leechinx@hotmail.com</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>National Taiwan University Children Hospital</name>
      <address>
        <city>Taipei</city>
        <zip>100</zip>
        <country>Taiwan</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Wang-Tso Lee, PhD</last_name>
      <phone>02-23123456</phone>
      <phone_ext>71618</phone_ext>
      <email>leeped@hotmail.com</email>
    </contact>
  </location>
  <location_countries>
    <country>Taiwan</country>
  </location_countries>
  <verification_date>April 2020</verification_date>
  <study_first_submitted>August 16, 2017</study_first_submitted>
  <study_first_submitted_qc>August 21, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">August 24, 2017</study_first_posted>
  <last_update_submitted>October 18, 2020</last_update_submitted>
  <last_update_submitted_qc>October 18, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">October 22, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Rett syndrome</keyword>
  <keyword>Tourette syndrome</keyword>
  <keyword>Probiotic</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Movement Disorders</mesh_term>
    <mesh_term>Tourette Syndrome</mesh_term>
    <mesh_term>Rett Syndrome</mesh_term>
    <mesh_term>Tic Disorders</mesh_term>
    <mesh_term>Syndrome</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </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/NCT03259971
org study id: 201703061MIPA
nct id: NCT03259971
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
Pediatric movement disorders comprise of a large number of different neurological diseases
      including Rett syndrome (RTT) and Tourette syndrome. Studies in the literature as well as our
      preliminary reports showed that Rett syndrome and Tourette syndrome/Tic disorders are
      associated with a dysbiosis of the gut microbiota compared to normal control. Probiotic
      Lactobacillus plantarum PS128 is a diet supplement that available for human consumption.
      Probiotic Lactobacillus plantarum PS128 had showed psychotropic effects such as ameliorate
      anxiety- and depression-like behaviors as well as altered the level of neurotransmitters such
      as dopamine in the brain in animal models, which might be through microbiota-gut-brain axis.
      Therefore, the purpose of this study is to access the possible neurobehavior effects of
      Probiotic Lactobacillus plantarum PS128 in Rett syndrome and Tic disorders/Tourette syndrome.
The study is a placebo-controlled double-blind randomized study, to determine the benefits of
      probiotic Lactobacillus plantarum PS128 vs placebo on symptoms for Tic disorders; and the
      symptoms, behavior, or cognition for Rett syndrome.

      Patients with the Rett syndrome and Tic disorders/Tourette syndrome will be recruited into
      our study.The study period will last 4 months for Rett syndrome patients, age one
      year-50years; while 2 months for Tic disorders/Tourette syndrome patient, age 5 years-18
      years.

      The study will be performed in National Taiwan University Children Hospital. The patients
      will have neuropsychological and gut microbiota evaluation before and at the end of the
      study. There will also be interim follow up evaluations each month after the patient start
      taking the probiotic or placebo.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
masking description: Randomized double blind placebo-controlled
measure: Neuropsychological test (Mullen Scales of Early Learning)
time frame: Change at four months from baseline
description: for Rett syndrome
measure: Yale Global Tic Severity Scale (YGTSS)
time frame: Change at 2 months from baseline
description: for Tic disorders
measure: RTT severity score
time frame: Change at four months from baseline
description: For Rett syndrome
measure: Dystonia status (Fahn Marsden rating scale/Unified Dystonia Rating Scale )
time frame: Visit 1, Visit 2, Visit 3, Visit 4 (Up to 4 months)
description: For Rett syndrome
measure: Anxiety, Depression, and Mood Scale (ADAMS)
time frame: Change at four months from baseline
description: For Rett syndrome
measure: Ghuman-Folstein Screen for Social Interaction (SSI)
time frame: Change at four months from baseline
description: For Rett syndrome
measure: Vineland Adaptive Behavioral scale
time frame: Change at four months from baseline
description: For Rett syndrome
measure: Early social communication scales
time frame: Change at four months from baseline
description: For Rett syndrome
measure: Pediatric Evaluation of Disability Inventory
time frame: Change at four months from baseline
description: For Rett syndrome
measure: Stool and gut microbiota evaluation
time frame: Change at four months from baseline
description: For Rett and Tic disorders
measure: Child Behavior Checklist (CBCL)
time frame: Change at 2 months from baseline
description: For Tic disorders
measure: Continuous performance test
time frame: Change at 2 months from baseline
description: For Tic disorders
measure: The Migraine Disability Assessment Test
time frame: Change at 2 months from baseline
description: For Tic disorders
measure: Children's Depression Inventory
time frame: Change at 2 months from baseline
description: For Tic disorders
measure: Obsessive-compulsive inventory
time frame: Change at 2 months from baseline
description: For Tic disorders
measure: Swanson, Nolan and Pehlam version IV
time frame: Change at 2 months from baseline
description: For Tic disorders
arm group label: Placebo (for tic disorder)
arm group type: Placebo Comparator
description: The placebo will be dispensed to equal the volume of 1 tablet of Probiotic PS128, which is taken orally in 2 divided doses, 12 hours apart during the study period of 2 months for Tic disorders.
arm group label: PS128 (tic disorder)
arm group type: Active Comparator
description: The Probiotic group in tic disorder will take Probiotic-Lactobacillus plantarum PS128, which contain 300mg (3x10^10 CFU) Lactobacillus plantarum PS128 and 100mg of Microcrystalline Cellulose in each tablet. It will be taken orally in 2 divided doses, 12 hours apart during the study period of 2 months for Tic disorders.
arm group label: Placebo (for Rett syndrome)
arm group type: Placebo Comparator
description: The placebo will be dispensed to equal the volume of 1 tablet of Probiotic PS128, which is taken orally in 2 divided doses, 12 hours apart during the study period of 4 months for Rett syndrome
arm group label: PS128 (Rett syndrome)
arm group type: Active Comparator
description: The Probiotic group will take Probiotic-Lactobacillus plantarum PS128, which contain 300mg (3x10^10 CFU) Lactobacillus plantarum PS128 and 100mg of Microcrystalline Cellulose in each tablet. It will be taken orally in 2 divided doses, 12 hours apart during the study period of 4 months for Rett Syndrome.
intervention type: Dietary Supplement
intervention name: Probiotic-Lactobacillus plantarum PS128
description: Probiotic supplement of Lactobacillus plantarum PS128 , 1 tablet , twice a day , 12 hrs apart, lasting 2 months for Tic disorders and 4 months for Rett syndrome
arm group label: PS128 (Rett syndrome)
arm group label: PS128 (tic disorder)
other name: Lactobacillus plantarum PS128
intervention type: Dietary Supplement
intervention name: Placebo
description: placebo , 1 tablet , twice a day , 12 hrs apart, lasting 2 months for Tic disorders and 4 months for Rett syndrome
arm group label: Placebo (for Rett syndrome)
arm group label: Placebo (for tic disorder)
criteria: 
gender: All
minimum age: 1 Year
maximum age: 50 Years
healthy volunteers: No
last name: Wang-Tso Lee, MD,PhD
role: Principal Investigator
affiliation: National Taiwan University Children Hospital
last name: Wang-Tso Lee, MD,PhD
phone: +886-223123456
phone ext: 71618
email: leeped@hotmail.com
last name: Lee Chin Wong, MD
phone: +886-223123456
phone ext: 71618
email: leechinx@hotmail.com
facility: 
status: Recruiting
contact: 
country: Taiwan
responsible party type: Sponsor
mesh term: Movement Disorders
mesh term: Tourette Syndrome
mesh term: Rett Syndrome
mesh term: Tic Disorders
mesh term: Syndrome
sharing ipd: No