<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/NCT03033199</url>
  </required_header>
  <id_info>
    <org_study_id>ITP-Microbiota</org_study_id>
    <nct_id>NCT03033199</nct_id>
  </id_info>
  <brief_title>Clinical Trial of Gut Microbiota in the Management of Immune Thrombocytopenia</brief_title>
  <official_title>A Multi-center Randomized Clinical Trial of Regulating Gut Microbiota by Probiotic Agents in Management of Immune Thrombocytopenia</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Shandong University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Jinan Central Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>The Second Hospital of Shandong University</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Qianfoshan Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Qingdao University</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Yantai Yuhuangding Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Shandong University</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Primary immune thrombocytopenia (ITP) is an acquired autoimmune bleeding disorder, accounting&#xD;
      for about 1/3 of clinical hemorrhagic diseases. Loss of immune tolerance leading to increased&#xD;
      platelet destruction and decreased platelet production is the main pathogenesis of ITP.&#xD;
      Dysbiosis of the gut microbiota was found in many autoimmune diseases like rheumatic&#xD;
      arthritis(RA),inflammatory bowel disease(IBD),multiple sclerosis and probiotic treatment or&#xD;
      fecal microbiota transplantation(FMT) which can regulate the gut microbiota has good clinical&#xD;
      efficacy in those disorders. One ITP patient with ulcerative colitis(UC) was treated with FMT&#xD;
      and got progressive but significant increase in platelet level and lasted for several years.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The investigators are undertaking a multicenter, single-arm study of 60 primary ITP adult&#xD;
      patients from 5 medical centers in China. All the participants are randomly divided into two&#xD;
      groups to orally intake either probiotic supplements (n = 30) or placebo (n = 30) for 4 weeks&#xD;
      in addition with high dose dexamethasone(40 mg/d for 4 days). Platelet count, bleeding and&#xD;
      other symptoms were evaluated before and after treatment. Adverse events are also recorded&#xD;
      throughout the study.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date>January 2017</start_date>
  <completion_date type="Anticipated">August 2018</completion_date>
  <primary_completion_date type="Anticipated">February 2018</primary_completion_date>
  <phase>Phase 2</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>Single (Participant)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Platelet count</measure>
    <time_frame>From date of randomization until the date of first documented progression,up to 12 months</time_frame>
    <description>R. A response (R) was defined as a sustained (≥ 3 months) platelet count ≥ 30×10^9/L without recurrence of thrombocytopenia</description>
  </primary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">60</enrollment>
  <condition>Immune Thrombocytopenia</condition>
  <arm_group>
    <arm_group_label>Probiotic Agent Combining HD-DXM</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>probiotic capsules containing three viable and freezedried strains-Lactobacillus acidophilus,Lactobacillus casei, and Bifidobacterium bifidum：2 capsules, bid x 4 weeks for one cycle. It will be given for one or two cycles.&#xD;
Dexamethasone 40mg per day, 4 consecutive day</description>
  </arm_group>
  <arm_group>
    <arm_group_label>HD-DXM</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Dexamethasone 40 mg per day, 4 consecutive days</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Probiotic Agent</intervention_name>
    <description>probiotic capsules containing three viable and freezedried strains-Lactobacillus acidophilus,Lactobacillus casei, and Bifidobacterium bifidum：2 capsules, bid x 4 weeks for one cycle. It will be given for one or two cycles.</description>
    <arm_group_label>Probiotic Agent Combining HD-DXM</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Dexamethasone</intervention_name>
    <description>Dexamethasone 40 mg per day, 4 consecutive days</description>
    <arm_group_label>HD-DXM</arm_group_label>
    <arm_group_label>Probiotic Agent Combining HD-DXM</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  need of treatment(s) (including, but not limited to, low dose of corticosteroids) to&#xD;
             minimize the risk of clinically significant bleeding. Need of on-demand or adjunctive&#xD;
             therapy alone does not qualify the patient as refractory&#xD;
&#xD;
          -  primary ITP confirmed by excluding other supervened causes of thrombocytopenia&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  pregnancy&#xD;
&#xD;
          -  hypertension&#xD;
&#xD;
          -  cardiovascular disease&#xD;
&#xD;
          -  diabetes&#xD;
&#xD;
          -  liver and kidney function impairment&#xD;
&#xD;
          -  HCV, HIV, HBsAg seropositive status&#xD;
&#xD;
          -  patients with systemic lupus erythematosus and/or antiphospholipid syndrome&#xD;
&#xD;
          -  patients with known gastro-intestinal bleeding.&#xD;
&#xD;
          -  use of antibiotics, prebiotics or probiotics in the past 4 weeks;&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>70 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Ming Hou</last_name>
    <role>Principal Investigator</role>
    <affiliation>Qilu Hospital, Shandong University</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Ming Hou</last_name>
    <email>houming@medmail.com.cn</email>
  </overall_contact>
  <location>
    <facility>
      <name>Shandong University Qilu hospital</name>
      <address>
        <city>Jinan</city>
        <state>Shandong</state>
        <zip>250012</zip>
        <country>China</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Ming Hou</last_name>
      <email>houming@medmail.com.cn</email>
    </contact>
    <investigator>
      <last_name>Ming Hou</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <reference>
    <citation>Kang Y, Cai Y, Zhang X, Kong X, Su J. Altered gut microbiota in RA: implications for treatment. Z Rheumatol. 2017 Jun;76(5):451-457. doi: 10.1007/s00393-016-0237-5.</citation>
    <PMID>27909795</PMID>
  </reference>
  <reference>
    <citation>Vaghef-Mehrabany E, Alipour B, Homayouni-Rad A, Sharif SK, Asghari-Jafarabadi M, Zavvari S. Probiotic supplementation improves inflammatory status in patients with rheumatoid arthritis. Nutrition. 2014 Apr;30(4):430-5. doi: 10.1016/j.nut.2013.09.007. Epub 2013 Dec 17.</citation>
    <PMID>24355439</PMID>
  </reference>
  <reference>
    <citation>Smits LP, Bouter KE, de Vos WM, Borody TJ, Nieuwdorp M. Therapeutic potential of fecal microbiota transplantation. Gastroenterology. 2013 Nov;145(5):946-53. doi: 10.1053/j.gastro.2013.08.058. Epub 2013 Sep 7.</citation>
    <PMID>24018052</PMID>
  </reference>
  <reference>
    <citation>Zamani B, Golkar HR, Farshbaf S, Emadi-Baygi M, Tajabadi-Ebrahimi M, Jafari P, Akhavan R, Taghizadeh M, Memarzadeh MR, Asemi Z. Clinical and metabolic response to probiotic supplementation in patients with rheumatoid arthritis: a randomized, double-blind, placebo-controlled trial. Int J Rheum Dis. 2016 Sep;19(9):869-79. doi: 10.1111/1756-185X.12888. Epub 2016 May 2.</citation>
    <PMID>27135916</PMID>
  </reference>
  <verification_date>January 2017</verification_date>
  <study_first_submitted>January 16, 2017</study_first_submitted>
  <study_first_submitted_qc>January 24, 2017</study_first_submitted_qc>
  <study_first_posted type="Estimate">January 26, 2017</study_first_posted>
  <last_update_submitted>January 24, 2017</last_update_submitted>
  <last_update_submitted_qc>January 24, 2017</last_update_submitted_qc>
  <last_update_posted type="Estimate">January 26, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Shandong University</investigator_affiliation>
    <investigator_full_name>Ming Hou</investigator_full_name>
    <investigator_title>Professor and Director</investigator_title>
  </responsible_party>
  <keyword>Gut microbiota</keyword>
  <keyword>Immune thrombocytopenia</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Thrombocytopenia</mesh_term>
    <mesh_term>Purpura, Thrombocytopenic, Idiopathic</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Dexamethasone</mesh_term>
  </intervention_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/NCT03033199
org study id: ITP-Microbiota
nct id: NCT03033199
lead sponsor: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
has dmc: Yes
Primary immune thrombocytopenia (ITP) is an acquired autoimmune bleeding disorder, accounting
      for about 1/3 of clinical hemorrhagic diseases. Loss of immune tolerance leading to increased
      platelet destruction and decreased platelet production is the main pathogenesis of ITP.
      Dysbiosis of the gut microbiota was found in many autoimmune diseases like rheumatic
      arthritis(RA),inflammatory bowel disease(IBD),multiple sclerosis and probiotic treatment or
      fecal microbiota transplantation(FMT) which can regulate the gut microbiota has good clinical
      efficacy in those disorders. One ITP patient with ulcerative colitis(UC) was treated with FMT
      and got progressive but significant increase in platelet level and lasted for several years.
The investigators are undertaking a multicenter, single-arm study of 60 primary ITP adult
      patients from 5 medical centers in China. All the participants are randomly divided into two
      groups to orally intake either probiotic supplements (n = 30) or placebo (n = 30) for 4 weeks
      in addition with high dose dexamethasone(40 mg/d for 4 days). Platelet count, bleeding and
      other symptoms were evaluated before and after treatment. Adverse events are also recorded
      throughout the study.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Single (Participant)
measure: Platelet count
time frame: From date of randomization until the date of first documented progression,up to 12 months
description: R. A response (R) was defined as a sustained (≥ 3 months) platelet count ≥ 30×10^9/L without recurrence of thrombocytopenia
arm group label: Probiotic Agent Combining HD-DXM
arm group type: Active Comparator
description: probiotic capsules containing three viable and freezedried strains-Lactobacillus acidophilus,Lactobacillus casei, and Bifidobacterium bifidum：2 capsules, bid x 4 weeks for one cycle. It will be given for one or two cycles.
Dexamethasone 40mg per day, 4 consecutive day
arm group label: HD-DXM
arm group type: Active Comparator
description: Dexamethasone 40 mg per day, 4 consecutive days
intervention type: Drug
intervention name: Probiotic Agent
description: probiotic capsules containing three viable and freezedried strains-Lactobacillus acidophilus,Lactobacillus casei, and Bifidobacterium bifidum：2 capsules, bid x 4 weeks for one cycle. It will be given for one or two cycles.
arm group label: Probiotic Agent Combining HD-DXM
intervention type: Drug
intervention name: Dexamethasone
description: Dexamethasone 40 mg per day, 4 consecutive days
arm group label: HD-DXM
arm group label: Probiotic Agent Combining HD-DXM
criteria: 
gender: All
minimum age: 18 Years
maximum age: 70 Years
healthy volunteers: No
last name: Ming Hou
role: Principal Investigator
affiliation: Qilu Hospital, Shandong University
last name: Ming Hou
email: houming@medmail.com.cn
facility: 
status: Recruiting
contact: 
investigator: 
country: China
citation: Kang Y, Cai Y, Zhang X, Kong X, Su J. Altered gut microbiota in RA: implications for treatment. Z Rheumatol. 2017 Jun;76(5):451-457. doi: 10.1007/s00393-016-0237-5.
PMID: 27909795
citation: Vaghef-Mehrabany E, Alipour B, Homayouni-Rad A, Sharif SK, Asghari-Jafarabadi M, Zavvari S. Probiotic supplementation improves inflammatory status in patients with rheumatoid arthritis. Nutrition. 2014 Apr;30(4):430-5. doi: 10.1016/j.nut.2013.09.007. Epub 2013 Dec 17.
PMID: 24355439
citation: Smits LP, Bouter KE, de Vos WM, Borody TJ, Nieuwdorp M. Therapeutic potential of fecal microbiota transplantation. Gastroenterology. 2013 Nov;145(5):946-53. doi: 10.1053/j.gastro.2013.08.058. Epub 2013 Sep 7.
PMID: 24018052
citation: Zamani B, Golkar HR, Farshbaf S, Emadi-Baygi M, Tajabadi-Ebrahimi M, Jafari P, Akhavan R, Taghizadeh M, Memarzadeh MR, Asemi Z. Clinical and metabolic response to probiotic supplementation in patients with rheumatoid arthritis: a randomized, double-blind, placebo-controlled trial. Int J Rheum Dis. 2016 Sep;19(9):869-79. doi: 10.1111/1756-185X.12888. Epub 2016 May 2.
PMID: 27135916
responsible party type: Principal Investigator
investigator affiliation: Shandong University
investigator full name: Ming Hou
investigator title: Professor and Director
mesh term: Thrombocytopenia
mesh term: Purpura, Thrombocytopenic, Idiopathic
mesh term: Dexamethasone
sharing ipd: No