<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/NCT01677923</url>
  </required_header>
  <id_info>
    <org_study_id>BE-2-1</org_study_id>
    <nct_id>NCT01677923</nct_id>
  </id_info>
  <brief_title>Obesity in Children and Adolescents: Associated Risks and Early Intervention</brief_title>
  <acronym>OCA</acronym>
  <official_title>Phase 3: Effect of Diet, Physical Activity and Insulin Sensitizer Metformin on Obesity and Associated Risks in Children and Adolescents.</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Lithuanian University of Health Sciences</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Lithuanian University of Health Sciences</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The investigators hypothesize that Metformin decreases weight, normalizes lipid profile and&#xD;
      increases insulin sensitivity; the study team hope to get better effect of weight decrease&#xD;
      and metabolic processes repair in the intensive treatment group with intervention of physical&#xD;
      activity, diet correction and Metformin use.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      During the first visit, study participants would follow the clinical investigation&#xD;
      (anthropometry, physical examination, blood tests (hormonal and biochemical state),&#xD;
      bioimpedance, ultrasound evaluation) and be attributed into 4 groups (matched for age,&#xD;
      gender, pubertal stage and BMI), 100 subjects in each group.&#xD;
&#xD;
        1. st group - control: during the first visit patients get standardized information on&#xD;
           healthy lifestyle, diet and exercise. Next visit (control) will be scheduled for the&#xD;
           clinical and laboratory evaluation after 12 months of intervention.&#xD;
&#xD;
        2. nd group - intensive diet and physical activity group: Children will be seen&#xD;
&#xD;
             1. by a dietician once a month for diet re-evaluation;&#xD;
&#xD;
             2. physical therapist, who will give physical activity course twice a week (1 h each).&#xD;
&#xD;
             3. pediatric endocrinologist every 3 months. Clinical and laboratory evaluation after&#xD;
                12 months of intervention.&#xD;
&#xD;
        3. rd group - intensive diet and physical activity group plus insulin sensitization:&#xD;
           Metformin will be prescribed for this group of study children in the doses of 1000&#xD;
           mg/day Children will be seen by&#xD;
&#xD;
             1. a dietician once a month for diet re-evaluation;&#xD;
&#xD;
             2. physical therapist, who will give physical activity course twice a week (1 h each);&#xD;
&#xD;
             3. pediatric endocrinologist every 3 month. Clinical and laboratory evaluation after&#xD;
                12 months of intervention.&#xD;
&#xD;
        4. th group- insulin sensitization without intensive diet and physical activity. Metformin&#xD;
           will be prescribed in the doses of 1000 mg/day after standardized information on healthy&#xD;
           lifestyle, diet and exercise during the first visit only. This group of children will be&#xD;
           seen by pediatric endocrinologist every 3 months.&#xD;
&#xD;
      Intervention duration - 12 months. In the case of Metformin intolerance, children will&#xD;
      continue the study in 2nd group.&#xD;
&#xD;
      Clinical and laboratory evaluation after 12 months of intervention.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>May 2013</start_date>
  <completion_date type="Actual">December 2015</completion_date>
  <primary_completion_date type="Actual">April 2014</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>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Body mass index changes</measure>
    <time_frame>12 months</time_frame>
    <description>decrease in body mass index</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Glucose homeostasis</measure>
    <time_frame>12 month</time_frame>
    <description>Insulin sensitivity increase, homeostasis model assessment (HOMA-IR) decrease, insulin and glucose concentrations normalisation</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Lipid profile</measure>
    <time_frame>12 months</time_frame>
    <description>Lipid profile normalisation</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Metabolic syndrome</measure>
    <time_frame>12 months</time_frame>
    <description>Metabolic syndrome prevalence and risks decrease</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Hepatosteatosis</measure>
    <time_frame>12 months</time_frame>
    <description>Hepatosteatosis prevalence decrease and liver function improvement, hepatic enzymes normalisation</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Polycystic ovary syndrome (PCOS) and hyperandrogenism in females</measure>
    <time_frame>12 months</time_frame>
    <description>PCOS clinical symptoms regression, menstrual cycle normalisation, hirsutism, androgens levels decreasing and estrogen, sex hormone-binding globulin (SHBG) levels increasing</description>
  </secondary_outcome>
  <other_outcome>
    <measure>safety</measure>
    <time_frame>12 months</time_frame>
    <description>how many patients will have adverse events and withdraw the Metformin due to their intolerance or clinical / biochemical relapse</description>
  </other_outcome>
  <number_of_arms>4</number_of_arms>
  <enrollment type="Actual">182</enrollment>
  <condition>Obesity</condition>
  <arm_group>
    <arm_group_label>Control without Metformin</arm_group_label>
    <arm_group_type>No Intervention</arm_group_type>
    <description>Conventional management of obesity including basic instructions on diet and physical activity</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Control with Metformin</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Conventional management of obesity including basic instructions on diet and physical activity plus Metformin treatment</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Intervention with Metformin</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Intensive physical activity course twice per week and monthly diet control by dietitian plus Metformin treatment.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Intervention without Metformin</arm_group_label>
    <arm_group_type>No Intervention</arm_group_type>
    <description>Intensive physical activity course twice per week and monthly diet control by dietitian</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Metformin</intervention_name>
    <description>Metformin 500 mg BID for 12 months</description>
    <arm_group_label>Control with Metformin</arm_group_label>
    <arm_group_label>Intervention with Metformin</arm_group_label>
    <other_name>Metforal</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Age 10-17 yrs;&#xD;
&#xD;
          -  Weight &gt; 85th percentile for age and gender (by IOTF);&#xD;
&#xD;
          -  Living in Kaunas and its region;&#xD;
&#xD;
          -  No obvious chronic diseases;&#xD;
&#xD;
          -  Not on steroid or other long-term treatment;&#xD;
&#xD;
          -  Informed consent of the patient and parents (official caregivers);&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Age less than 10 or above 17 yrs;&#xD;
&#xD;
          -  Diagnosis of type 1 diabetes;&#xD;
&#xD;
          -  Chronic illness that may affect physical activity and metabolic profile;&#xD;
&#xD;
          -  Insulin treatment;&#xD;
&#xD;
          -  Steroid treatment;&#xD;
&#xD;
          -  Planning to move from Kaunas or its region in the period of 1 year;&#xD;
&#xD;
          -  Protocol refused by the patient or his parents;&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>10 Years</minimum_age>
    <maximum_age>18 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Rasa Verkauskiene, Professor</last_name>
    <role>Study Chair</role>
    <affiliation>Lithuanian University of Health Sciences Hospital, Endocrinology Unit</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Rasa Verkauskiene</name>
      <address>
        <city>Kaunas</city>
        <state>Eiveniu str. 2</state>
        <zip>LT50009</zip>
        <country>Lithuania</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Lithuania</country>
  </location_countries>
  <verification_date>March 2016</verification_date>
  <study_first_submitted>July 30, 2012</study_first_submitted>
  <study_first_submitted_qc>August 29, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 3, 2012</study_first_posted>
  <last_update_submitted>March 2, 2016</last_update_submitted>
  <last_update_submitted_qc>March 2, 2016</last_update_submitted_qc>
  <last_update_posted type="Estimate">March 4, 2016</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Lithuanian University of Health Sciences</investigator_affiliation>
    <investigator_full_name>Rasa Verkauskiene</investigator_full_name>
    <investigator_title>Professor, Head of Department and Institute of Endocrinology, Lithuanian UHS</investigator_title>
  </responsible_party>
  <keyword>weight</keyword>
  <keyword>body mass index</keyword>
  <keyword>lipid profile</keyword>
  <keyword>glucose profile</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Obesity</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Metformin</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Undecided</sharing_ipd>
    <ipd_description>Study results are in progress with statistical analysis</ipd_description>
  </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/NCT01677923
org study id: BE-2-1
nct id: NCT01677923
lead sponsor: 
has dmc: Yes
The investigators hypothesize that Metformin decreases weight, normalizes lipid profile and
      increases insulin sensitivity; the study team hope to get better effect of weight decrease
      and metabolic processes repair in the intensive treatment group with intervention of physical
      activity, diet correction and Metformin use.
During the first visit, study participants would follow the clinical investigation
      (anthropometry, physical examination, blood tests (hormonal and biochemical state),
      bioimpedance, ultrasound evaluation) and be attributed into 4 groups (matched for age,
      gender, pubertal stage and BMI), 100 subjects in each group.

        1. st group - control: during the first visit patients get standardized information on
           healthy lifestyle, diet and exercise. Next visit (control) will be scheduled for the
           clinical and laboratory evaluation after 12 months of intervention.

        2. nd group - intensive diet and physical activity group: Children will be seen

             1. by a dietician once a month for diet re-evaluation;

             2. physical therapist, who will give physical activity course twice a week (1 h each).

             3. pediatric endocrinologist every 3 months. Clinical and laboratory evaluation after
                12 months of intervention.

        3. rd group - intensive diet and physical activity group plus insulin sensitization:
           Metformin will be prescribed for this group of study children in the doses of 1000
           mg/day Children will be seen by

             1. a dietician once a month for diet re-evaluation;

             2. physical therapist, who will give physical activity course twice a week (1 h each);

             3. pediatric endocrinologist every 3 month. Clinical and laboratory evaluation after
                12 months of intervention.

        4. th group- insulin sensitization without intensive diet and physical activity. Metformin
           will be prescribed in the doses of 1000 mg/day after standardized information on healthy
           lifestyle, diet and exercise during the first visit only. This group of children will be
           seen by pediatric endocrinologist every 3 months.

      Intervention duration - 12 months. In the case of Metformin intolerance, children will
      continue the study in 2nd group.

      Clinical and laboratory evaluation after 12 months of intervention.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Body mass index changes
time frame: 12 months
description: decrease in body mass index
measure: Glucose homeostasis
time frame: 12 month
description: Insulin sensitivity increase, homeostasis model assessment (HOMA-IR) decrease, insulin and glucose concentrations normalisation
measure: Lipid profile
time frame: 12 months
description: Lipid profile normalisation
measure: Metabolic syndrome
time frame: 12 months
description: Metabolic syndrome prevalence and risks decrease
measure: Hepatosteatosis
time frame: 12 months
description: Hepatosteatosis prevalence decrease and liver function improvement, hepatic enzymes normalisation
measure: Polycystic ovary syndrome (PCOS) and hyperandrogenism in females
time frame: 12 months
description: PCOS clinical symptoms regression, menstrual cycle normalisation, hirsutism, androgens levels decreasing and estrogen, sex hormone-binding globulin (SHBG) levels increasing
measure: safety
time frame: 12 months
description: how many patients will have adverse events and withdraw the Metformin due to their intolerance or clinical / biochemical relapse
arm group label: Control without Metformin
arm group type: No Intervention
description: Conventional management of obesity including basic instructions on diet and physical activity
arm group label: Control with Metformin
arm group type: Experimental
description: Conventional management of obesity including basic instructions on diet and physical activity plus Metformin treatment
arm group label: Intervention with Metformin
arm group type: Experimental
description: Intensive physical activity course twice per week and monthly diet control by dietitian plus Metformin treatment.
arm group label: Intervention without Metformin
arm group type: No Intervention
description: Intensive physical activity course twice per week and monthly diet control by dietitian
intervention type: Drug
intervention name: Metformin
description: Metformin 500 mg BID for 12 months
arm group label: Control with Metformin
arm group label: Intervention with Metformin
other name: Metforal
criteria: 
gender: All
minimum age: 10 Years
maximum age: 18 Years
healthy volunteers: No
last name: Rasa Verkauskiene, Professor
role: Study Chair
affiliation: Lithuanian University of Health Sciences Hospital, Endocrinology Unit
facility: 
country: Lithuania
responsible party type: Principal Investigator
investigator affiliation: Lithuanian University of Health Sciences
investigator full name: Rasa Verkauskiene
investigator title: Professor, Head of Department and Institute of Endocrinology, Lithuanian UHS
mesh term: Obesity
mesh term: Metformin
sharing ipd: Undecided
ipd description: Study results are in progress with statistical analysis