<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/NCT03033290</url>
  </required_header>
  <id_info>
    <org_study_id>CORPG1F0011</org_study_id>
    <nct_id>NCT03033290</nct_id>
  </id_info>
  <brief_title>Traditional Chinese Medicine on Gut Microbiota and Allergic Diseases</brief_title>
  <official_title>Effect of Traditional Chinese Medicine on Gut Microbiota, Physical Constitution, and Allergic Diseases</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Chang Gung Memorial Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Chang Gung Memorial Hospital</source>
  <oversight_info>
    <has_dmc>Yes</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>
      Allergic rhinitis is an importance disease in Taiwan with its high incidence about 20-30% and&#xD;
      gradually increased annually. However, symptom relapse still bothered the majority of&#xD;
      patients though there were certain advances in western medicine. In addition, side effects of&#xD;
      western medicine, such as lethargy, mouth dryness were noted. Traditional Chinese medicine,&#xD;
      especially qi-tonifying regimen has been used and proved benefit to the allergic diseases by&#xD;
      many researchers.This study will provide the evidences of gut microbiota changes and&#xD;
      immune-modulatory effects of BZYQT for the treatment of allergic rhinitis.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Recently studies reported that gut microbiota is related to the human immunity modulation of&#xD;
      allergic diseases. Investigators are interested to know weather qi-tonifying herbal medicine&#xD;
      is through the changes of gut microbiota to modulate human immunity. In this study, a&#xD;
      double-blinded, randomized, placebo control design is applied and total 60 perennial allergic&#xD;
      rhinitis patients will be enrolled in our study. All subjects will be divided into&#xD;
      Bu-Zhong-Yi-Qi-Tang (BZYQT) and placebo control groups, 40 and 20 subjects each. Subjects of&#xD;
      BZYQT group will receive capsule of BZYQT, 4gm tid, 12gm a day, while control group will&#xD;
      receive similar placebo capsule with same scheme. Total 2 months treatment course will be&#xD;
      done. Gut microbiota will be assayed before and after 2 months treatment. Additionally,&#xD;
      various parameters for immunologic response will be checked before and after the treatment,&#xD;
      including the total IgE amount, the ratio of CD4/CD8 of T lymphocytes, the profile of&#xD;
      cytokine such as IL-10 and IL-12 as well as functional change of dendritic cells and T cells.&#xD;
      Results will be analyzed statistically including gender analysis. This study will provide the&#xD;
      evidences of gut microbiota changes and immune-modulatory effects of BZYQT for the treatment&#xD;
      of allergic rhinitis.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date type="Actual">January 10, 2018</start_date>
  <completion_date type="Anticipated">July 31, 2020</completion_date>
  <primary_completion_date type="Anticipated">July 31, 2020</primary_completion_date>
  <phase>Phase 3</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>Triple (Participant, Care Provider, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Changes in allergic rhinitis symptom severity</measure>
    <time_frame>Assessment of symptom severity on Day 0 and 2 months after completing treatment</time_frame>
    <description>Sino-nasal Outcome Test (SNOT-22)</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Improvement of fatigue</measure>
    <time_frame>Assessment of fatigue severity on Day 0 and 2 months after completing treatment</time_frame>
    <description>Fatigue Severity Scale</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Improvement of life quality</measure>
    <time_frame>Assessment of life quality on Day 0 and 2 months after completing treatment</time_frame>
    <description>SF-36</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Detection of gut microbiota</measure>
    <time_frame>Assessment of gut microbiota on Day 0 and 2 months after completing treatment</time_frame>
    <description>use cecal stool DNA purification and quantification of cecal microbiota by quantitative PCR (qPCR). Using V3-V5 16S rRNA amplification; Processing of NGS data; Operational Taxonomic Units (OTUs) cluster; Taxonomic profiling</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in serum total and mite specific IgE</measure>
    <time_frame>Assessment of serologic markers on Day 0 and 2 months after completing treatment</time_frame>
    <description>check serum total IgE and mite specific IgE (KIU/l)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>T Cells measurement</measure>
    <time_frame>Assessment of CD4/CD8 on Day 0 and 2 months after completing treatment</time_frame>
    <description>check CD4 / CD8 by flowcytometry</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Measurement of cytokines produced by polymorphonuclear leukocytes</measure>
    <time_frame>Assessment of serologic markers on Day 0 and 2 months after completing treatment</time_frame>
    <description>check sICAM-1,IL-8,PGE2, LTC4</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Measurement of cytokines produced by monocytes and lymphocytes</measure>
    <time_frame>Assessment of serologic markers on Day 0 and 2 months after completing treatment</time_frame>
    <description>IL-4、IL-5、IL-10、IL-13、IFN-γ</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Detection of dendritic cell function</measure>
    <time_frame>Assessment of serologic markers on Day 0 and 2 months after completing treatment</time_frame>
    <description>check IL-10 and IL-12 level</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">60</enrollment>
  <condition>Allergic Rhinitis</condition>
  <arm_group>
    <arm_group_label>Bu-Zhong-Yi-Qi-Tang (BZYQT)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>capsule of BZYQT, 4gm tid, 12gm a day for 2 months</description>
  </arm_group>
  <arm_group>
    <arm_group_label>placebo control</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>similar placebo capsule 4gm tid, 12gm a day for 2 months</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Bu-Zhong-Yi-Qi-Tang</intervention_name>
    <description>Qi-tonifying regimen of traditional Chinese herbal medicine</description>
    <arm_group_label>Bu-Zhong-Yi-Qi-Tang (BZYQT)</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>placebo</intervention_name>
    <description>placebo control</description>
    <arm_group_label>placebo control</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. With at least one of the following clinical symptoms: itchy nose, sneeze, rhinorrhea,&#xD;
             nasal congestion&#xD;
&#xD;
          2. Diagnosed as intermittent allergic rhinitis (Less than 4 days per week and for less&#xD;
             than 4 weeks)&#xD;
&#xD;
          3. CAP panel :allergy to mite&#xD;
&#xD;
          4. Will to complete questionnaires and take medicine as schedule in this study&#xD;
&#xD;
          5. Volunteer for study enrollment and sign inform consent&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Under treatment of western medicine including steroid, antihistamine, leukotriene&#xD;
             inhibitor, immunosuppressant or stop above medication less than one month&#xD;
&#xD;
          2. Under acute inflammatory disease such as pneumonia, sinusitis, bronchitis and so on&#xD;
&#xD;
          3. vasomotor type allergic rhinitis&#xD;
&#xD;
          4. history of allergy or adverse effect to Chinese herbs, poor compliance of herbal&#xD;
             medicine&#xD;
&#xD;
          5. severe organ function impairment, such as heart failure, liver failure, renal failure&#xD;
             (eGFR &lt;60 mL/min/1.73 m2)&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>20 Years</minimum_age>
    <maximum_age>60 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Sien-hung Yang, Ph.D.</last_name>
    <role>Study Director</role>
    <affiliation>Chang Gung Memorial Hospital, Taoyuan, Taiwan</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Sien-hung Yang, Ph.D.</last_name>
    <phone>+886-3-3196200</phone>
    <phone_ext>2611</phone_ext>
    <email>dryang@ms1.hinet.net</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>YI-Hsuan Lin, M.D.</last_name>
    <phone>+886-3-3196200</phone>
    <phone_ext>2611</phone_ext>
    <email>cynthiajobo@gmail.com</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Chang Gung Memorial Hospital</name>
      <address>
        <city>Taoyuan</city>
        <country>Taiwan</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Yi-Hsuan Lin, M.D.</last_name>
      <phone>+886-3-3196200</phone>
      <phone_ext>2611</phone_ext>
      <email>cynthiajobo@gmail.com</email>
    </contact>
    <investigator>
      <last_name>Sien-hung Yang, Ph.D.</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>Taiwan</country>
  </location_countries>
  <reference>
    <citation>Hwang BF, Jaakkola JJ, Lee YL, Lin YC, Guo YL. Relation between air pollution and allergic rhinitis in Taiwanese schoolchildren. Respir Res. 2006 Feb 9;7(1):23. doi: 10.1186/1465-9921-7-23.</citation>
    <PMID>16469096</PMID>
  </reference>
  <reference>
    <citation>Yang SH, Hong CY, Yu CL. Decreased serum IgE level, decreased IFN-gamma and IL-5 but increased IL-10 production, and suppressed cyclooxygenase 2 mRNA expression in patients with perennial allergic rhinitis after treatment with a new mixed formula of Chinese herbs. Int Immunopharmacol. 2001 Jun;1(6):1173-82. doi: 10.1016/s1567-5769(01)00051-0.</citation>
    <PMID>11407311</PMID>
  </reference>
  <reference>
    <citation>Yang SH, Hong CY, Yu CL. The stimulatory effects of nasal discharge from patients with perennial allergic rhinitis on normal human neutrophils are normalized after treatment with a new mixed formula of Chinese herbs. Int Immunopharmacol. 2002 Nov;2(12):1627-39. doi: 10.1016/s1567-5769(02)00133-9.</citation>
    <PMID>12469937</PMID>
  </reference>
  <reference>
    <citation>Yang SH, Yu CL, Chen YL, Chiao SL, Chen ML. Traditional Chinese medicine, Xin-yi-san, reduces nasal symptoms of patients with perennial allergic rhinitis by its diverse immunomodulatory effects. Int Immunopharmacol. 2010 Aug;10(8):951-8. doi: 10.1016/j.intimp.2010.05.008. Epub 2010 May 28.</citation>
    <PMID>20546945</PMID>
  </reference>
  <reference>
    <citation>Kuroiwa A, Liou S, Yan H, Eshita A, Naitoh S, Nagayama A. Effect of a traditional Japanese herbal medicine, hochu-ekki-to (Bu-Zhong-Yi-Qi Tang), on immunity in elderly persons. Int Immunopharmacol. 2004 Feb;4(2):317-24. doi: 10.1016/j.intimp.2003.12.004.</citation>
    <PMID>14996423</PMID>
  </reference>
  <reference>
    <citation>Yang SH, Kao TI, Chiang BL, Chen HY, Chen KH, Chen JL. Immune-modulatory effects of bu-zhong-yi-qi-tang in ovalbumin-induced murine model of allergic asthma. PLoS One. 2015 Jun 2;10(6):e0127636. doi: 10.1371/journal.pone.0127636. eCollection 2015.</citation>
    <PMID>26035827</PMID>
  </reference>
  <results_reference>
    <citation>Xie MQ, Liu J, Long Z, Tian DF, Zhao CQ, Yang PC. Modulation of immune tolerance with a Chinese traditional prescription inhibits allergic rhinitis in mice. N Am J Med Sci. 2011 Nov;3(11):503-7. doi: 10.4297/najms.2011.3503.</citation>
    <PMID>22361496</PMID>
  </results_reference>
  <verification_date>January 2018</verification_date>
  <study_first_submitted>May 31, 2016</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, 2018</last_update_submitted>
  <last_update_submitted_qc>January 24, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">January 26, 2018</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Chang Gung Memorial Hospital</investigator_affiliation>
    <investigator_full_name>YANG SIEN-HUNG</investigator_full_name>
    <investigator_title>Director of Department of Traditional Chinese Medicine</investigator_title>
  </responsible_party>
  <keyword>Qi-tonifying regimen</keyword>
  <keyword>immune-modulation</keyword>
  <keyword>gut microbiota</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Rhinitis</mesh_term>
    <mesh_term>Rhinitis, Allergic</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>Undecided</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/NCT03033290
org study id: CORPG1F0011
nct id: NCT03033290
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
Allergic rhinitis is an importance disease in Taiwan with its high incidence about 20-30% and
      gradually increased annually. However, symptom relapse still bothered the majority of
      patients though there were certain advances in western medicine. In addition, side effects of
      western medicine, such as lethargy, mouth dryness were noted. Traditional Chinese medicine,
      especially qi-tonifying regimen has been used and proved benefit to the allergic diseases by
      many researchers.This study will provide the evidences of gut microbiota changes and
      immune-modulatory effects of BZYQT for the treatment of allergic rhinitis.
Recently studies reported that gut microbiota is related to the human immunity modulation of
      allergic diseases. Investigators are interested to know weather qi-tonifying herbal medicine
      is through the changes of gut microbiota to modulate human immunity. In this study, a
      double-blinded, randomized, placebo control design is applied and total 60 perennial allergic
      rhinitis patients will be enrolled in our study. All subjects will be divided into
      Bu-Zhong-Yi-Qi-Tang (BZYQT) and placebo control groups, 40 and 20 subjects each. Subjects of
      BZYQT group will receive capsule of BZYQT, 4gm tid, 12gm a day, while control group will
      receive similar placebo capsule with same scheme. Total 2 months treatment course will be
      done. Gut microbiota will be assayed before and after 2 months treatment. Additionally,
      various parameters for immunologic response will be checked before and after the treatment,
      including the total IgE amount, the ratio of CD4/CD8 of T lymphocytes, the profile of
      cytokine such as IL-10 and IL-12 as well as functional change of dendritic cells and T cells.
      Results will be analyzed statistically including gender analysis. This study will provide the
      evidences of gut microbiota changes and immune-modulatory effects of BZYQT for the treatment
      of allergic rhinitis.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Triple (Participant, Care Provider, Investigator)
measure: Changes in allergic rhinitis symptom severity
time frame: Assessment of symptom severity on Day 0 and 2 months after completing treatment
description: Sino-nasal Outcome Test (SNOT-22)
measure: Improvement of fatigue
time frame: Assessment of fatigue severity on Day 0 and 2 months after completing treatment
description: Fatigue Severity Scale
measure: Improvement of life quality
time frame: Assessment of life quality on Day 0 and 2 months after completing treatment
description: SF-36
measure: Detection of gut microbiota
time frame: Assessment of gut microbiota on Day 0 and 2 months after completing treatment
description: use cecal stool DNA purification and quantification of cecal microbiota by quantitative PCR (qPCR). Using V3-V5 16S rRNA amplification; Processing of NGS data; Operational Taxonomic Units (OTUs) cluster; Taxonomic profiling
measure: Change in serum total and mite specific IgE
time frame: Assessment of serologic markers on Day 0 and 2 months after completing treatment
description: check serum total IgE and mite specific IgE (KIU/l)
measure: T Cells measurement
time frame: Assessment of CD4/CD8 on Day 0 and 2 months after completing treatment
description: check CD4 / CD8 by flowcytometry
measure: Measurement of cytokines produced by polymorphonuclear leukocytes
time frame: Assessment of serologic markers on Day 0 and 2 months after completing treatment
description: check sICAM-1,IL-8,PGE2, LTC4
measure: Measurement of cytokines produced by monocytes and lymphocytes
time frame: Assessment of serologic markers on Day 0 and 2 months after completing treatment
description: IL-4、IL-5、IL-10、IL-13、IFN-γ
measure: Detection of dendritic cell function
time frame: Assessment of serologic markers on Day 0 and 2 months after completing treatment
description: check IL-10 and IL-12 level
arm group label: Bu-Zhong-Yi-Qi-Tang (BZYQT)
arm group type: Experimental
description: capsule of BZYQT, 4gm tid, 12gm a day for 2 months
arm group label: placebo control
arm group type: Placebo Comparator
description: similar placebo capsule 4gm tid, 12gm a day for 2 months
intervention type: Drug
intervention name: Bu-Zhong-Yi-Qi-Tang
description: Qi-tonifying regimen of traditional Chinese herbal medicine
arm group label: Bu-Zhong-Yi-Qi-Tang (BZYQT)
intervention type: Drug
intervention name: placebo
description: placebo control
arm group label: placebo control
criteria: 
gender: All
minimum age: 20 Years
maximum age: 60 Years
healthy volunteers: No
last name: Sien-hung Yang, Ph.D.
role: Study Director
affiliation: Chang Gung Memorial Hospital, Taoyuan, Taiwan
last name: Sien-hung Yang, Ph.D.
phone: +886-3-3196200
phone ext: 2611
email: dryang@ms1.hinet.net
last name: YI-Hsuan Lin, M.D.
phone: +886-3-3196200
phone ext: 2611
email: cynthiajobo@gmail.com
facility: 
status: Recruiting
contact: 
investigator: 
country: Taiwan
citation: Hwang BF, Jaakkola JJ, Lee YL, Lin YC, Guo YL. Relation between air pollution and allergic rhinitis in Taiwanese schoolchildren. Respir Res. 2006 Feb 9;7(1):23. doi: 10.1186/1465-9921-7-23.
PMID: 16469096
citation: Yang SH, Hong CY, Yu CL. Decreased serum IgE level, decreased IFN-gamma and IL-5 but increased IL-10 production, and suppressed cyclooxygenase 2 mRNA expression in patients with perennial allergic rhinitis after treatment with a new mixed formula of Chinese herbs. Int Immunopharmacol. 2001 Jun;1(6):1173-82. doi: 10.1016/s1567-5769(01)00051-0.
PMID: 11407311
citation: Yang SH, Hong CY, Yu CL. The stimulatory effects of nasal discharge from patients with perennial allergic rhinitis on normal human neutrophils are normalized after treatment with a new mixed formula of Chinese herbs. Int Immunopharmacol. 2002 Nov;2(12):1627-39. doi: 10.1016/s1567-5769(02)00133-9.
PMID: 12469937
citation: Yang SH, Yu CL, Chen YL, Chiao SL, Chen ML. Traditional Chinese medicine, Xin-yi-san, reduces nasal symptoms of patients with perennial allergic rhinitis by its diverse immunomodulatory effects. Int Immunopharmacol. 2010 Aug;10(8):951-8. doi: 10.1016/j.intimp.2010.05.008. Epub 2010 May 28.
PMID: 20546945
citation: Kuroiwa A, Liou S, Yan H, Eshita A, Naitoh S, Nagayama A. Effect of a traditional Japanese herbal medicine, hochu-ekki-to (Bu-Zhong-Yi-Qi Tang), on immunity in elderly persons. Int Immunopharmacol. 2004 Feb;4(2):317-24. doi: 10.1016/j.intimp.2003.12.004.
PMID: 14996423
citation: Yang SH, Kao TI, Chiang BL, Chen HY, Chen KH, Chen JL. Immune-modulatory effects of bu-zhong-yi-qi-tang in ovalbumin-induced murine model of allergic asthma. PLoS One. 2015 Jun 2;10(6):e0127636. doi: 10.1371/journal.pone.0127636. eCollection 2015.
PMID: 26035827
citation: Xie MQ, Liu J, Long Z, Tian DF, Zhao CQ, Yang PC. Modulation of immune tolerance with a Chinese traditional prescription inhibits allergic rhinitis in mice. N Am J Med Sci. 2011 Nov;3(11):503-7. doi: 10.4297/najms.2011.3503.
PMID: 22361496
responsible party type: Principal Investigator
investigator affiliation: Chang Gung Memorial Hospital
investigator full name: YANG SIEN-HUNG
investigator title: Director of Department of Traditional Chinese Medicine
mesh term: Rhinitis
mesh term: Rhinitis, Allergic
sharing ipd: Undecided