<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/NCT03281096</url>
  </required_header>
  <id_info>
    <org_study_id>XJLL 2016 001</org_study_id>
    <nct_id>NCT03281096</nct_id>
  </id_info>
  <brief_title>A Research of Berberine Hydrochloride to Prevent Colorectal Adenomas in Patients With Previous Colorectal Cancer</brief_title>
  <official_title>A Randomized Trial of Berberine Hydrochloride to Prevent Colorectal Adenomas in Patients With Previous Colorectal Cancer</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Xijing Hospital of Digestive Diseases</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Xijing Hospital of Digestive Diseases</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>
      Experimental studies in animals and observational studies in humans suggest that&#xD;
      fusobacterium nucleatum is associates with stages of colorectal neoplasia development, and&#xD;
      Berberine Hydrochloride could rescue Fusobacterium nucleatum-induced colorectal tumorigenesis&#xD;
      by modulating the tumor microenvironment. Whether regular Berberine Hydrochloride use may&#xD;
      decrease the risk of colorectal adenomas, the precursors to most colorectal cancers is worth&#xD;
      to further study.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The prevalence of colorectal adenomas is high in our country, as is the incidence of&#xD;
      colorectal cancer. It is well-known that colorectal adenomas are the precursor of colorectal&#xD;
      cancer and that removing them will prevent colorectal cancer. Because most colorectal cancers&#xD;
      arise from benign adenomas, adenomas have been used as surrogate end points in prevention&#xD;
      trials. Berberine hydrochloride, which is an alkaloid extracted from Rhizoma coptidis, has&#xD;
      been traditionally used in Chinese medicine to treat gastrointestinal infections, due to its&#xD;
      antimicrobial properties. Previous clinical research and animal studies have demonstrated the&#xD;
      anti-tumor action of Berberine hydrochloride. Persons with a history of colorectal cancer&#xD;
      might constitute a group at higher risk for adenomas and thus be particularly suitable for a&#xD;
      study of the chemopreventive effects of Berberine hydrochloride. Here, a randomized,&#xD;
      double-blind, placebo-controlled trial was designed to determine whether the daily use of 300&#xD;
      mg of berberine hydrochloride could decreases the occurrence of new colorectal adenomas among&#xD;
      patients with a history of colorectal cancer.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">August 29, 2017</start_date>
  <completion_date type="Actual">March 1, 2021</completion_date>
  <primary_completion_date type="Actual">October 12, 2020</primary_completion_date>
  <phase>Phase 2/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>Prevention</primary_purpose>
    <masking>Triple (Participant, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Cumulative the colorectal adenoma incidence rate during Berberine hydrochloride or placebo treatment in patients with a history of colorectal cancer</measure>
    <time_frame>From baseline to 3 years.</time_frame>
    <description>The proportion of patients in whom one or more colorectal adenomas were investigated during the period from one year after randomization through the anticipated surveillance follow-up examination. The development of colorectal adenomas was assessed with an Olympus flexible video colonoscopy. One endoscopic investigator, who did not review the records of previous examinations, made all the assessments.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Cumulative the numbers or diameters of those new colorectal adenomas during Berberine hydrochloride or placebo treatment in patients with a history of colorectal cancer</measure>
    <time_frame>From baseline to 3 years.</time_frame>
    <description>The numbers or diameters of those new colorectal adenomas were analyzed during the period from one year after randomization through the anticipated surveillance follow-up examination. The endoscopic investigator, who did not review the records of previous examinations, counted the total number of colorectal adenomas, and the examination was recorded on videotape. The diameter of those colorectal adenomas was measured in millimeters with a graduated scale passed through the colonoscopy biopsy channel.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">1000</enrollment>
  <condition>Colorectal Adenomas</condition>
  <arm_group>
    <arm_group_label>Berberine hydrochloride group</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Berberine hydrochloride 300mg tablet by mouth, two times per day for 3 years</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>identical-appearing placebo 300mg tablet by mouth, two times per day for 3 years</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Berberine hydrochloride</intervention_name>
    <description>patients take the Berberine hydrochloride 300mg tablet by mouth, 2 times a day with 3 years.</description>
    <arm_group_label>Berberine hydrochloride group</arm_group_label>
    <other_name>Berberine hydrochloride tablet (&quot;Sine Tianping&quot;)</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>pill manufactured to mmic Berberine hydrochloride 100mg tablet</description>
    <arm_group_label>Placebo</arm_group_label>
    <other_name>Placebo (for Berberine hydrochloride)</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Patients aged 18-80 years&#xD;
&#xD;
          -  Patients who had histologically documented colon or rectal cancer with a low risk of&#xD;
             recurrent disease&#xD;
&#xD;
          -  Patients with Dukes' stage A or B1 colon or rectal cancer (tumor-node-metastasis [TNM]&#xD;
             stage T1 to T2, N0, M0) who had undergone curative resection of the primary tumor were&#xD;
             immediately eligible for enrollment&#xD;
&#xD;
          -  Patients with Dukes' stage B2 or C (T3 to T4, N0 to N1, M0) colon or rectal cancer who&#xD;
             had undergone curative resection of the primary tumor were eligible if they had been&#xD;
             free of disease for more than five years after curative surgery&#xD;
&#xD;
          -  Eligible participants had to have undergone, after adequate preparation, colonoscopy&#xD;
             to the cecum (or small-bowel anastomosis), with removal of all polyps, within four&#xD;
             months before study entry&#xD;
&#xD;
          -  Patients were eligible if they were in good general health, with an expected survival&#xD;
             of at least five years; willing to provide and able to understand informed consent and&#xD;
             to cooperate with the study procedures; not currently enrolled in a clinical trial of&#xD;
             colon-cancer treatment or other chemoprevention trial; and not pregnant or nursing.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Patients who are hypersensitive or intolerant to the drugs&#xD;
&#xD;
          -  Patients had familial polyposis&#xD;
&#xD;
          -  Patients had invasive cancer other than nonmelanoma skin cancer within 5 years before&#xD;
             the intake appointment&#xD;
&#xD;
          -  Patients with diabetes mellitus, severe renal disease or cardiovascular disease&#xD;
             (defined by a New York Heart Association functional classof III or IV)&#xD;
&#xD;
          -  Patients with hypercalcemia or urolithiasis&#xD;
&#xD;
          -  Patients had a history of inflammatory bowel disease&#xD;
&#xD;
          -  Patients with hemolytic anemia and glucose -6- phosphate dehydrogenase deficiency&#xD;
&#xD;
          -  Patients had received immunosuppressive therapy within the previous 6 months&#xD;
&#xD;
          -  Patients had clinically obvious narcotic or alcohol dependence during the previous 6&#xD;
             months&#xD;
&#xD;
          -  Patients had used NSAIDs including aspirin at any dose on 3 or more days per month&#xD;
             during each of the 3 months before enrollment or for a period of 36 days in the&#xD;
             previous year; or had a history of stroke, transient ischemic attacks, angina,&#xD;
             myocardial infarction, or atherosclerotic peripheral vascular disease&#xD;
&#xD;
          -  Pregnant women, women during breast-feeding period, or women with expect pregnancy&#xD;
&#xD;
          -  Patients with a history of subtotal gastrectomy or partial bowel resection&#xD;
&#xD;
          -  Patients who are not able to cooperate&#xD;
&#xD;
          -  Patients with any condition that could be worsened by supplemental Berberine&#xD;
             hydrochloride&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>80 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Weizhong Wang, MD,PH.D</last_name>
    <role>Principal Investigator</role>
    <affiliation>Xijing digestive surgery center</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Xijing Hospital of Digestive Disease</name>
      <address>
        <city>Xi'an</city>
        <state>Shaanxi</state>
        <zip>710032</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <verification_date>July 2022</verification_date>
  <study_first_submitted>August 30, 2017</study_first_submitted>
  <study_first_submitted_qc>September 12, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">September 13, 2017</study_first_posted>
  <last_update_submitted>July 24, 2022</last_update_submitted>
  <last_update_submitted_qc>July 24, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">July 27, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Xijing Hospital of Digestive Diseases</investigator_affiliation>
    <investigator_full_name>xiaohua li</investigator_full_name>
    <investigator_title>Director of colorectal surgery center</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Adenoma</mesh_term>
  </condition_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/NCT03281096
org study id: XJLL 2016 001
nct id: NCT03281096
lead sponsor: 
is fda regulated drug: No
is fda regulated device: No
Experimental studies in animals and observational studies in humans suggest that
      fusobacterium nucleatum is associates with stages of colorectal neoplasia development, and
      Berberine Hydrochloride could rescue Fusobacterium nucleatum-induced colorectal tumorigenesis
      by modulating the tumor microenvironment. Whether regular Berberine Hydrochloride use may
      decrease the risk of colorectal adenomas, the precursors to most colorectal cancers is worth
      to further study.
The prevalence of colorectal adenomas is high in our country, as is the incidence of
      colorectal cancer. It is well-known that colorectal adenomas are the precursor of colorectal
      cancer and that removing them will prevent colorectal cancer. Because most colorectal cancers
      arise from benign adenomas, adenomas have been used as surrogate end points in prevention
      trials. Berberine hydrochloride, which is an alkaloid extracted from Rhizoma coptidis, has
      been traditionally used in Chinese medicine to treat gastrointestinal infections, due to its
      antimicrobial properties. Previous clinical research and animal studies have demonstrated the
      anti-tumor action of Berberine hydrochloride. Persons with a history of colorectal cancer
      might constitute a group at higher risk for adenomas and thus be particularly suitable for a
      study of the chemopreventive effects of Berberine hydrochloride. Here, a randomized,
      double-blind, placebo-controlled trial was designed to determine whether the daily use of 300
      mg of berberine hydrochloride could decreases the occurrence of new colorectal adenomas among
      patients with a history of colorectal cancer.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Prevention
masking: Triple (Participant, Investigator, Outcomes Assessor)
measure: Cumulative the colorectal adenoma incidence rate during Berberine hydrochloride or placebo treatment in patients with a history of colorectal cancer
time frame: From baseline to 3 years.
description: The proportion of patients in whom one or more colorectal adenomas were investigated during the period from one year after randomization through the anticipated surveillance follow-up examination. The development of colorectal adenomas was assessed with an Olympus flexible video colonoscopy. One endoscopic investigator, who did not review the records of previous examinations, made all the assessments.
measure: Cumulative the numbers or diameters of those new colorectal adenomas during Berberine hydrochloride or placebo treatment in patients with a history of colorectal cancer
time frame: From baseline to 3 years.
description: The numbers or diameters of those new colorectal adenomas were analyzed during the period from one year after randomization through the anticipated surveillance follow-up examination. The endoscopic investigator, who did not review the records of previous examinations, counted the total number of colorectal adenomas, and the examination was recorded on videotape. The diameter of those colorectal adenomas was measured in millimeters with a graduated scale passed through the colonoscopy biopsy channel.
arm group label: Berberine hydrochloride group
arm group type: Experimental
description: Berberine hydrochloride 300mg tablet by mouth, two times per day for 3 years
arm group label: Placebo
arm group type: Placebo Comparator
description: identical-appearing placebo 300mg tablet by mouth, two times per day for 3 years
intervention type: Drug
intervention name: Berberine hydrochloride
description: patients take the Berberine hydrochloride 300mg tablet by mouth, 2 times a day with 3 years.
arm group label: Berberine hydrochloride group
other name: Berberine hydrochloride tablet ("Sine Tianping")
intervention type: Drug
intervention name: Placebo
description: pill manufactured to mmic Berberine hydrochloride 100mg tablet
arm group label: Placebo
other name: Placebo (for Berberine hydrochloride)
criteria: 
gender: All
minimum age: 18 Years
maximum age: 80 Years
healthy volunteers: No
last name: Weizhong Wang, MD,PH.D
role: Principal Investigator
affiliation: Xijing digestive surgery center
facility: 
country: China
responsible party type: Principal Investigator
investigator affiliation: Xijing Hospital of Digestive Diseases
investigator full name: xiaohua li
investigator title: Director of colorectal surgery center
mesh term: Adenoma