<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/NCT01725490</url>
  </required_header>
  <id_info>
    <org_study_id>4-2012-0491</org_study_id>
    <nct_id>NCT01725490</nct_id>
  </id_info>
  <brief_title>The Chemopreventive Effect of Metformin in Patients With Familial Adenomatous Polyposis: Double Blinded Randomized Controlled Study</brief_title>
  <sponsors>
    <lead_sponsor>
      <agency>Yonsei University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Yonsei University</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Familial adenomatous polyposis (FAP) leads to adenomas and eventual adenocarcinomas in colon&#xD;
      and less frequently, duodenum. Chemopreventive strategies have been studied in FAP patients&#xD;
      to delay the development of adenomas and cancers. The non-steroidal anti-inflammatory drugs&#xD;
      (NSAIDs) and selective cyclooxygenase-2 inhibitor have shown the regression of colorectal and&#xD;
      duodenal adenomas in FAP patients. However, these drugs showed gastrointestinal damage and&#xD;
      cardiovascular risks, and new preventive strategies are needed. Metformin, a biguanide, which&#xD;
      is widely used for treating diabetes mellitus, has recently been suggested to have a&#xD;
      suppressive effect on tumorigenesis via mTOR-inhibiting pathway, and have no significant&#xD;
      safety issues in long term use. The investigators devised a double-blind randomized&#xD;
      controlled trial to evaluate the effect of metformin on polyps of colorectum and duodenum in&#xD;
      non-diabetic FAP patients.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">February 15, 2013</start_date>
  <completion_date type="Actual">August 30, 2020</completion_date>
  <primary_completion_date type="Actual">August 30, 2020</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>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>the mean percentage change of the number and size of polyps in colon and/or duodenum.</measure>
    <time_frame>After seven-month administration of metformin/placebo, colonoscopy/sigmoidoscopy and upper gastrointestinal endoscopy will be performed.</time_frame>
    <description>At the base-line endoscopy, India-ink tattoo will be placed in the ascending colon, sigmoid colon/rectum, and duodenum. In case of patient with retained rectum after colectomy and ileorectal anastomosis, sigmoidoscopy will be performed. The base-line and seven-month endoscopic examination will be recorded, and photographs will be taken at the tattoo-marked area and used for measurements of the number and size of polyps. The diameter of a polyp will be measured with the aid of biopsy forceps included in the photographic field, and only distinct polyps at least 2 mm in diameter will be counted.</description>
  </primary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">34</enrollment>
  <condition>Familial Adenomatous Polyposis</condition>
  <arm_group>
    <arm_group_label>metformin 500mg daily (arm A)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>metformin 1500mg daily (arm B)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>an identical- appearing placebo (arm C)</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Metformin</intervention_name>
    <description>Patients will be randomly assigned in a 2:2:1 ratio to receive metformin or identical-appearing placebo tablets orally for 7 months: metformin 500mg once and placebo twice a day in arm A, metformin 500mg three times a day in arm B, and placebo three times a day in arm C.</description>
    <arm_group_label>metformin 500mg daily (arm A)</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Metformin</intervention_name>
    <description>Patients will be randomly assigned in a 2:2:1 ratio to receive metformin or identical-appearing placebo tablets orally for 7 months: metformin 500mg once and placebo twice a day in arm A, metformin 500mg three times a day in arm B, and placebo three times a day in arm C.</description>
    <arm_group_label>metformin 1500mg daily (arm B)</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Patients will be randomly assigned in a 2:2:1 ratio to receive metformin or identical-appearing placebo tablets orally for 7 months: metformin 500mg once and placebo twice a day in arm A, metformin 500mg three times a day in arm B, and placebo three times a day in arm C.</description>
    <arm_group_label>an identical- appearing placebo (arm C)</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Patients with familial adenomatous polyposis(FAP) who are 20 to 65 years of age.&#xD;
&#xD;
          2. FAP patients who have colonic or duodenal polyp&#xD;
&#xD;
          3. FAP patients who have five or more polyps 2mm or more in diameter in endoscopic&#xD;
             examination.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. FAP patients who had a history of colectomy within the previous 12 months or need to&#xD;
             undergo colectomy within 8 months after randomization.&#xD;
&#xD;
          2. FAP patients with malignant disease, including colorectal cancer.&#xD;
&#xD;
          3. FAP patients who used NSAIDs (non-steroidal anti-inflammatory drugs) or aspirin three&#xD;
             or more times a week within 6 months of randomization. 4. FAP patients with diabetes&#xD;
             mellitus. 5. Pregnant or breast-feeding patients. 6. Patients with abnormal results of&#xD;
             serum laboratory tests (renal function and liver function test) and significant&#xD;
             infectious or respiratory diseases.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>20 Years</minimum_age>
    <maximum_age>65 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Department of Internal Medicine, Yonsei University College of Medicine</name>
      <address>
        <city>Seoul</city>
        <zip>120-752</zip>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Korea, Republic of</country>
  </location_countries>
  <verification_date>September 2021</verification_date>
  <study_first_submitted>October 31, 2012</study_first_submitted>
  <study_first_submitted_qc>November 7, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">November 12, 2012</study_first_posted>
  <last_update_submitted>September 16, 2021</last_update_submitted>
  <last_update_submitted_qc>September 16, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">September 20, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>chemoprevention, metformin, familial adenomatous polyposis</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Adenomatous Polyposis Coli</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Metformin</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/NCT01725490
org study id: 4-2012-0491
nct id: NCT01725490
lead sponsor: 
has dmc: No
Familial adenomatous polyposis (FAP) leads to adenomas and eventual adenocarcinomas in colon
      and less frequently, duodenum. Chemopreventive strategies have been studied in FAP patients
      to delay the development of adenomas and cancers. The non-steroidal anti-inflammatory drugs
      (NSAIDs) and selective cyclooxygenase-2 inhibitor have shown the regression of colorectal and
      duodenal adenomas in FAP patients. However, these drugs showed gastrointestinal damage and
      cardiovascular risks, and new preventive strategies are needed. Metformin, a biguanide, which
      is widely used for treating diabetes mellitus, has recently been suggested to have a
      suppressive effect on tumorigenesis via mTOR-inhibiting pathway, and have no significant
      safety issues in long term use. The investigators devised a double-blind randomized
      controlled trial to evaluate the effect of metformin on polyps of colorectum and duodenum in
      non-diabetic FAP patients.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: the mean percentage change of the number and size of polyps in colon and/or duodenum.
time frame: After seven-month administration of metformin/placebo, colonoscopy/sigmoidoscopy and upper gastrointestinal endoscopy will be performed.
description: At the base-line endoscopy, India-ink tattoo will be placed in the ascending colon, sigmoid colon/rectum, and duodenum. In case of patient with retained rectum after colectomy and ileorectal anastomosis, sigmoidoscopy will be performed. The base-line and seven-month endoscopic examination will be recorded, and photographs will be taken at the tattoo-marked area and used for measurements of the number and size of polyps. The diameter of a polyp will be measured with the aid of biopsy forceps included in the photographic field, and only distinct polyps at least 2 mm in diameter will be counted.
arm group label: metformin 500mg daily (arm A)
arm group type: Experimental
arm group label: metformin 1500mg daily (arm B)
arm group type: Experimental
arm group label: an identical- appearing placebo (arm C)
arm group type: Placebo Comparator
intervention type: Drug
intervention name: Metformin
description: Patients will be randomly assigned in a 2:2:1 ratio to receive metformin or identical-appearing placebo tablets orally for 7 months: metformin 500mg once and placebo twice a day in arm A, metformin 500mg three times a day in arm B, and placebo three times a day in arm C.
arm group label: metformin 500mg daily (arm A)
intervention type: Drug
intervention name: Metformin
description: Patients will be randomly assigned in a 2:2:1 ratio to receive metformin or identical-appearing placebo tablets orally for 7 months: metformin 500mg once and placebo twice a day in arm A, metformin 500mg three times a day in arm B, and placebo three times a day in arm C.
arm group label: metformin 1500mg daily (arm B)
intervention type: Drug
intervention name: Placebo
description: Patients will be randomly assigned in a 2:2:1 ratio to receive metformin or identical-appearing placebo tablets orally for 7 months: metformin 500mg once and placebo twice a day in arm A, metformin 500mg three times a day in arm B, and placebo three times a day in arm C.
arm group label: an identical- appearing placebo (arm C)
criteria: 
gender: All
minimum age: 20 Years
maximum age: 65 Years
healthy volunteers: No
facility: 
country: Korea, Republic of
responsible party type: Sponsor
mesh term: Adenomatous Polyposis Coli
mesh term: Metformin