<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/NCT01695850</url>
  </required_header>
  <id_info>
    <org_study_id>HHSRF09101501</org_study_id>
    <nct_id>NCT01695850</nct_id>
  </id_info>
  <brief_title>A Double-blinded,Double-dummy Clinical Trial of Chinese Herbal Medicine (MaZiRenWan) for Functional Constipation</brief_title>
  <official_title>Chinese Herbal Medicine (MaZhiRenWan) for Functional Constipation: a Prospective, Double-blinded, Double-dummy, Randomized Controlled Study</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Hong Kong Baptist University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Queen Elizabeth Hospital, Hong Kong</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Prince of Wales Hospital, Shatin, Hong Kong</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Hong Kong Baptist University</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The objective of this study is to evaluate the efficacy and safety of a Chinese herbal&#xD;
      proprietary medicine, MaZiRenWan (MZRW), by comparing with stimulant laxative western&#xD;
      medicine (WM), senna, and placebo for patients with functional constipation (FC) in excessive&#xD;
      TCM syndrome.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Functional constipation (FC) is a common clinical complaint. Despite the effectiveness of&#xD;
      MaZiRenWan (MZRW) for alleviating FC symptoms has been proofed in the previous study.Given&#xD;
      the results of the dose determination study and placebo-controlled study of MZRW, we&#xD;
      hypothesize that MZRW is more useful than senna (senokot), a commonly used WM drug for&#xD;
      constipation, for FC patients in excessive TCM syndrome.This is a prospective, double-blind,&#xD;
      double dummy, randomized, controlled trial. After a 2-week run-in, eligible FC patients (Rome&#xD;
      III) in excessive TCM syndrome will randomly be assigned to CHM arm (MZRW and WM placebo), WM&#xD;
      arm (senna and CHM placebo) or placebo arm (CHM placebo and WM placebo). Patients will&#xD;
      undergo an 8-week treatment and an 8-week follow-up.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>June 2013</start_date>
  <completion_date type="Actual">August 2015</completion_date>
  <primary_completion_date type="Actual">August 2015</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>Triple (Participant, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>the responder rate for CSBM during the treatment period</measure>
    <time_frame>8 weeks</time_frame>
    <description>a clinically meaningful endpoint by combining an objective measure (number of bowel movement) with a subjective measure (feelings of patients as to completeness of defecation,Patients with a mean increase of ≧1 complete spontaneous bowel movement(CSBM)/wk compared with the baseline(wk1-2) will be defined as responders</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>the responder rate for CSBM during the follow-up period</measure>
    <time_frame>8 weeks</time_frame>
    <description>Participants with a mean increase of complete spontaneous bowel movement (CSBM)&gt;=1 movement per week compared with the last 14 days of the run-in period were defined as responders</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Individual assessment of constipation and related symptoms</measure>
    <time_frame>18 weeks</time_frame>
    <description>severity of constipation, sensation of straining, incomplete evacuation, bloating, abdominal pain / cramping, nausea, and passing of gas) was recorded using a 7-point ordinal scale (0 = not at all and 6 = very severe</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>the changes of colonic transit time</measure>
    <time_frame>18 weeks</time_frame>
    <description>It is estimated by using a commercially available radio-opaque Sitzmarks capsule (Konsyl Pharmaceuticals, US). Each gelatine capsule contained 24 barium sulphate embedded polyvinyl chloride markers measuring 1mmx4.5mm. Plain radiographs of the abdomen will be obtained after the swallow of capsule for five days (120 hours) before and after 8 weeks treatment period.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Global symptom assessment</measure>
    <time_frame>18 weeks</time_frame>
    <description>Participants were asked to rate their impression of change in constipation by comparing with their baseline (Wk2) at the visits during the treatment (Wk6), end of treatment (Wk10) and end of follow-up (Wk18) with scores from 0 to 6 represented markedly worse or better respectively. The response categories were collapsed to simply &quot;improved&quot; for score 4 to 6, &quot;same&quot; for score 3 or &quot;worse&quot; for score 0 to 2.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Success of blinding</measure>
    <time_frame>18 weeks</time_frame>
    <description>the success of blinding is evaluated for both investigator and patients as to whether CHM, WM or placebo had been taken</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>safety profiles</measure>
    <time_frame>18 weeks</time_frame>
    <description>Assessed by determining the important adverse events reported in the participants ' diaries, follow-up interviews,and clinical laboratory evaluationse.g., liver and renal function.</description>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">291</enrollment>
  <condition>Functional Constipation</condition>
  <condition>Gastrointestinal Disorders</condition>
  <arm_group>
    <arm_group_label>MZRW</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>MZRW is composed of Fructus Cannabis (HuoMaRen), Radix et Rhizoma Rhei (DaHuang), Radix Paeoniae Alba (BaiShao), Semen Armeniacae Amarum (KuXingRen), Fructus Aurantii Immaturus (ZhiShi) and Cortex Magnoliae Officinalis (HouPo).</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Senna</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Senna is a stimulant laxative which facilitates the passage of stools by altering intestinal electrolyte transport and increasing intestinal motor activity.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Placebo MZRW and Placebo Senna</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>MZRW</intervention_name>
    <description>Patients are instructed to dissolve a sachet of granules (7.5g) in 150ml of hot water; they take this solution orally twice daily for 8 weeks.</description>
    <arm_group_label>MZRW</arm_group_label>
    <other_name>Hemp Seed Pill</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Senna</intervention_name>
    <description>Patients are instructed to take 2 tablets at the bedtime for 8 weeks.</description>
    <arm_group_label>Senna</arm_group_label>
    <other_name>Senokot</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>placebo</intervention_name>
    <description>The placebo MZRW is made from dextrin (76.03%), tea essence (23.61%), gardenin (0.02%) and caramel (0.34%) to achieve color, smell, taste and texture comparable to MZRW granules.The placebo Senna is made of starch and colour to achieve comparable appearance to Senokot.</description>
    <arm_group_label>MZRW</arm_group_label>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_label>Senna</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  either gender aged 18 to 65 years&#xD;
&#xD;
          -  have FC diagnosed as Rome III criterial&#xD;
&#xD;
          -  have diagnosis of Excessive Constipation according to the TCM theory&#xD;
&#xD;
          -  complete spontaneous bowel movement (CSBM) ≦2times/w&#xD;
&#xD;
          -  severity of constipation≧3pts (7 pts scale from 0 to 6pts) and the overall scoring of&#xD;
             constipation-related symptoms≧6pts (6items in 7pts scale) for self symptom assessment&#xD;
             in the run-in period&#xD;
&#xD;
          -  normal colonic evaluation (colonoscopy or barium enema) within 12 months&#xD;
&#xD;
          -  normal liver and renal function in blood test within 3 months&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  drug-induced constipation&#xD;
&#xD;
          -  secondary causes of constipation (i.e. medical history of diabetes mellitus and&#xD;
             thyroid disease)&#xD;
&#xD;
          -  abdominal surgery (i.e. Caesarean operation)&#xD;
&#xD;
          -  severe diseases (i.e. cancer and acute present asthma)&#xD;
&#xD;
          -  allergy to CHM (i.e. G6PD deficiency), senna and tartrazine&#xD;
&#xD;
          -  pregnancy or breast-feeding&#xD;
&#xD;
          -  psychiatric or addictive disorders&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>65 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Zhao Xiang Bian, MD, Ph. D</last_name>
    <role>Principal Investigator</role>
    <affiliation>School of Chinese Medicine, Hong Kong Baptist University</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>School of Chinese Medicine, Hong Kong Baptist University</name>
      <address>
        <city>Hong Kong</city>
        <state>Hong Kong</state>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <verification_date>May 2020</verification_date>
  <study_first_submitted>September 27, 2012</study_first_submitted>
  <study_first_submitted_qc>September 27, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 28, 2012</study_first_posted>
  <last_update_submitted>May 10, 2020</last_update_submitted>
  <last_update_submitted_qc>May 10, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">May 12, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Hong Kong Baptist University</investigator_affiliation>
    <investigator_full_name>ZhaoXiang Bian</investigator_full_name>
    <investigator_title>Professor</investigator_title>
  </responsible_party>
  <keyword>Randomized controlled trial</keyword>
  <keyword>Drugs,Chinese Herbal</keyword>
  <keyword>Constipation/drug therapy</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Gastrointestinal Diseases</mesh_term>
    <mesh_term>Digestive System Diseases</mesh_term>
    <mesh_term>Constipation</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Sennosides</mesh_term>
  </intervention_browse>
  <!-- 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/NCT01695850
org study id: HHSRF09101501
nct id: NCT01695850
lead sponsor: 
collaborator: 
collaborator: 
has dmc: Yes
The objective of this study is to evaluate the efficacy and safety of a Chinese herbal
      proprietary medicine, MaZiRenWan (MZRW), by comparing with stimulant laxative western
      medicine (WM), senna, and placebo for patients with functional constipation (FC) in excessive
      TCM syndrome.
Functional constipation (FC) is a common clinical complaint. Despite the effectiveness of
      MaZiRenWan (MZRW) for alleviating FC symptoms has been proofed in the previous study.Given
      the results of the dose determination study and placebo-controlled study of MZRW, we
      hypothesize that MZRW is more useful than senna (senokot), a commonly used WM drug for
      constipation, for FC patients in excessive TCM syndrome.This is a prospective, double-blind,
      double dummy, randomized, controlled trial. After a 2-week run-in, eligible FC patients (Rome
      III) in excessive TCM syndrome will randomly be assigned to CHM arm (MZRW and WM placebo), WM
      arm (senna and CHM placebo) or placebo arm (CHM placebo and WM placebo). Patients will
      undergo an 8-week treatment and an 8-week follow-up.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Triple (Participant, Investigator, Outcomes Assessor)
measure: the responder rate for CSBM during the treatment period
time frame: 8 weeks
description: a clinically meaningful endpoint by combining an objective measure (number of bowel movement) with a subjective measure (feelings of patients as to completeness of defecation,Patients with a mean increase of ≧1 complete spontaneous bowel movement(CSBM)/wk compared with the baseline(wk1-2) will be defined as responders
measure: the responder rate for CSBM during the follow-up period
time frame: 8 weeks
description: Participants with a mean increase of complete spontaneous bowel movement (CSBM)>=1 movement per week compared with the last 14 days of the run-in period were defined as responders
measure: Individual assessment of constipation and related symptoms
time frame: 18 weeks
description: severity of constipation, sensation of straining, incomplete evacuation, bloating, abdominal pain / cramping, nausea, and passing of gas) was recorded using a 7-point ordinal scale (0 = not at all and 6 = very severe
measure: the changes of colonic transit time
time frame: 18 weeks
description: It is estimated by using a commercially available radio-opaque Sitzmarks capsule (Konsyl Pharmaceuticals, US). Each gelatine capsule contained 24 barium sulphate embedded polyvinyl chloride markers measuring 1mmx4.5mm. Plain radiographs of the abdomen will be obtained after the swallow of capsule for five days (120 hours) before and after 8 weeks treatment period.
measure: Global symptom assessment
time frame: 18 weeks
description: Participants were asked to rate their impression of change in constipation by comparing with their baseline (Wk2) at the visits during the treatment (Wk6), end of treatment (Wk10) and end of follow-up (Wk18) with scores from 0 to 6 represented markedly worse or better respectively. The response categories were collapsed to simply "improved" for score 4 to 6, "same" for score 3 or "worse" for score 0 to 2.
measure: Success of blinding
time frame: 18 weeks
description: the success of blinding is evaluated for both investigator and patients as to whether CHM, WM or placebo had been taken
measure: safety profiles
time frame: 18 weeks
description: Assessed by determining the important adverse events reported in the participants ' diaries, follow-up interviews,and clinical laboratory evaluationse.g., liver and renal function.
arm group label: MZRW
arm group type: Experimental
description: MZRW is composed of Fructus Cannabis (HuoMaRen), Radix et Rhizoma Rhei (DaHuang), Radix Paeoniae Alba (BaiShao), Semen Armeniacae Amarum (KuXingRen), Fructus Aurantii Immaturus (ZhiShi) and Cortex Magnoliae Officinalis (HouPo).
arm group label: Senna
arm group type: Active Comparator
description: Senna is a stimulant laxative which facilitates the passage of stools by altering intestinal electrolyte transport and increasing intestinal motor activity.
arm group label: Placebo
arm group type: Placebo Comparator
description: Placebo MZRW and Placebo Senna
intervention type: Drug
intervention name: MZRW
description: Patients are instructed to dissolve a sachet of granules (7.5g) in 150ml of hot water; they take this solution orally twice daily for 8 weeks.
arm group label: MZRW
other name: Hemp Seed Pill
intervention type: Drug
intervention name: Senna
description: Patients are instructed to take 2 tablets at the bedtime for 8 weeks.
arm group label: Senna
other name: Senokot
intervention type: Drug
intervention name: placebo
description: The placebo MZRW is made from dextrin (76.03%), tea essence (23.61%), gardenin (0.02%) and caramel (0.34%) to achieve color, smell, taste and texture comparable to MZRW granules.The placebo Senna is made of starch and colour to achieve comparable appearance to Senokot.
arm group label: MZRW
arm group label: Placebo
arm group label: Senna
criteria: 
gender: All
minimum age: 18 Years
maximum age: 65 Years
healthy volunteers: No
last name: Zhao Xiang Bian, MD, Ph. D
role: Principal Investigator
affiliation: School of Chinese Medicine, Hong Kong Baptist University
facility: 
country: China
responsible party type: Principal Investigator
investigator affiliation: Hong Kong Baptist University
investigator full name: ZhaoXiang Bian
investigator title: Professor
mesh term: Gastrointestinal Diseases
mesh term: Digestive System Diseases
mesh term: Constipation
mesh term: Sennosides