<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/NCT03027726</url>
  </required_header>
  <id_info>
    <org_study_id>DEP2016-78377-R</org_study_id>
    <nct_id>NCT03027726</nct_id>
  </id_info>
  <brief_title>Prevention of Diabetes in Overweight/Obese Preadolescent Children</brief_title>
  <acronym>PREDIKID</acronym>
  <official_title>Prevention of Diabetes in Overweight/Obese Preadolescent Children Through a Family-based Intervention Program Including Supervised Exercise; the PREDIKID Study</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of the Basque Country (UPV/EHU)</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Ministerio de Economía y Competitividad, Spain</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Universidad Pública de Navarra</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>University of the Basque Country (UPV/EHU)</source>
  <oversight_info>
    <has_dmc>No</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>
      Background: The global pandemic obesity has led to increased risk for prediabetes and type 2&#xD;
      diabetes (T2D).&#xD;
&#xD;
      Objectives: (i) To evaluate the effect of a 22 weeks multidisciplinary intervention program&#xD;
      including exercise on T2D risk in pre-adolescents with high risk to develop T2D, and (ii) To&#xD;
      identify the profile of microRNA in circulating exosomes and in blood peripheral mononuclear&#xD;
      cells in pre-adolescents with high risk to develop T2D and its response to a&#xD;
      multidisciplinary intervention program including exercise.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Background: The global pandemic obesity has led to increased risk for prediabetes and type 2&#xD;
      diabetes (T2D).&#xD;
&#xD;
      Objectives: (i) To evaluate the effect of a 22 weeks multidisciplinary intervention program&#xD;
      including exercise on T2D risk in pre-adolescents with high risk to develop T2D, and (ii) To&#xD;
      identify the profile of microRNA in circulating exosomes and in blood peripheral mononuclear&#xD;
      cells in pre-adolescents with high risk to develop T2D and its response to a&#xD;
      multidisciplinary intervention program including exercise.&#xD;
&#xD;
      Design, participants and methods: A total of 84 children with high risk of type 2 diabetes&#xD;
      mellitus aged 8-12 years will be included and randomly assigned to control (N=42) or&#xD;
      intervention (N=42) groups. The control group will receive a family-based lifestyle education&#xD;
      and psycho-educational program (2 days/month), while the intervention group will attend the&#xD;
      same lifestyle education and psycho-educational program plus the exercise program (3&#xD;
      days/week). The duration of training sessions will be 90 min of exercise, including warm-up,&#xD;
      moderate to vigorous aerobic activities, and strength exercises. The following measurements&#xD;
      will be evaluated at baseline prior to randomization and after the intervention: fasting,&#xD;
      insulin glucose, and hemoglobin A1c; total and abdominal fat (dual X-ray absorptiometry);&#xD;
      pancreatic, hepatic and visceral fat (magnetic resonance imaging); systolic and diastolic&#xD;
      blood pressure; fasting leptin, adiponectin, fibroblast growth factor-21, fetuin-A,&#xD;
      hs-C-reactive protein, tumor necrosis factor-alfa, interleukin (IL)-1beta and IL-6 and lipid&#xD;
      profile; carotid intima-media thickness (ultrasonography), microRNA expression in circulating&#xD;
      exosomes and in blood peripheral mononuclear cells (MiSeq-Illumina); functional peak aerobic&#xD;
      capacity (cardiopulmonary exercise testing and 20m shuttle run test). Changes in dietary&#xD;
      habits (food frequency questionnaire and two non-consecutive 24h recalls), physical activity&#xD;
      and sleep (accelerometry); sex, age, socioeconomic status and pubertal status will be used as&#xD;
      potential confounders.&#xD;
&#xD;
      Discussion/Conclusions: Early prevention and identification of children with high risk to&#xD;
      develop T2D could help to reduce the morbidity and mortality associated with the disease.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">March 7, 2017</start_date>
  <completion_date type="Actual">September 15, 2018</completion_date>
  <primary_completion_date type="Actual">September 15, 2018</primary_completion_date>
  <phase>N/A</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>Insulin resistance</measure>
    <time_frame>Baseline and at the end of the 22 weeks of intervention</time_frame>
    <description>The Homeostasis model assessment index will be calculated as fasting insulin concentration (microU/mL) x fasting glucose concentration (mmol/L)/22.5.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>microRNA expression in circulating exosomes and in blood peripheral mononuclear cells</measure>
    <time_frame>Baseline and at the end of the 22 weeks of intervention</time_frame>
    <description>The expression of miRNAs will be measured in circulating exosomes and in white blood cells (MiSeq-Ilumina)</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Ectopic fat: pancreatic and liver fat accumulation</measure>
    <time_frame>Baseline and at the end of the 22 weeks of intervention</time_frame>
    <description>Hepatic and pancreatic fat will be measured by magnetic resonance</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Total, abdominal and visceral adiposity</measure>
    <time_frame>Baseline and at the end of the 22 weeks of intervention</time_frame>
    <description>Total and abdominal adiposity will be measured by dual energy X-ray absorptiometry. Visceral adiposity will be measured by magnetic resonance imaging</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Anthropometry and blood pressure</measure>
    <time_frame>Baseline and at the end of the 22 weeks of intervention</time_frame>
    <description>Body mass, height and waist circumference will be measured following standard protocols at least twice until consistent measures will be obtained and thereafter, body mass index (BMI) and waist to height ratio will be calculated. Systolic and diastolic blood pressure measurements will be performed following the recommendations for children using an arm blood pressure oscillometric monitor device</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Cardiorespiratory fitness</measure>
    <time_frame>Baseline and at the end of the 22 weeks of intervention</time_frame>
    <description>Cardiorespiratory fitness will be assessed by two different tests: (i) The 20m shuttle run test in which the equation reported by Léger et al. will be used to estimate the maximum oxygen consumption (VO2max, ml/kg/min) from the 20m shuttle run test scores, and (ii) Direct cardiopulmonary exercise progressive incremental treadmill test using the modified American College of Sports Medicine protocol with respiratory gas analysis to exhaustion</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Carotid intima-media thickness</measure>
    <time_frame>Baseline and at the end of the 22 weeks of intervention</time_frame>
    <description>carotid intima-media thickness will be measured by ultrasound according to international recommendations.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Inflammation and biochemical cardiovascular disease risk factors</measure>
    <time_frame>Baseline and at the end of the 22 weeks of intervention</time_frame>
    <description>Fasting lipid profile (total-, HDL- and LDL-cholesterol, and triglycerides), glucose, insulin, and hemoglobin A1c, cytokines (e.g. tumor necrosis factor alpha and IL-6) adipokines (e.g leptin and adiponectin), hepatokines (fetuin-A and fibroblast growth factor-21), liver enzymes (alanine aminotransferase, aspartate aminotransferase and gamma-glutamyl transferase), C-reactive protein, thyroid hormones (thyroid stimulating hormone, triiodothyronine and free thyroxine), urea, bilirubin and uric acid</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Confounding variable: puberty stage</measure>
    <time_frame>Baseline</time_frame>
    <description>The pediatrician will evaluate Tanner staging by direct examination with breast palpation in girls and testicular measurement by orchidometer in boys.</description>
  </other_outcome>
  <other_outcome>
    <measure>Confounding variable:physical activity and sleep</measure>
    <time_frame>Baseline and at the end of the 22 weeks of intervention</time_frame>
    <description>Children will wear an activity monitor on the wrist for 7 consecutive days for 24 hours to record physical activity intensity levels and patterns, as well as sleeping habits and participants will also complete a diary log</description>
  </other_outcome>
  <other_outcome>
    <measure>Confounding variable: dietary habits</measure>
    <time_frame>Baseline and at the end of the 22 weeks of intervention</time_frame>
    <description>Dietary intake will be evaluated by two non-consecutive 24h recalls within a period of seven days by nutritionists and a validated food frequency questionnaire</description>
  </other_outcome>
  <other_outcome>
    <measure>Confounding variable: sedentary behaviors</measure>
    <time_frame>Baseline and at the end of the 22 weeks of intervention</time_frame>
    <description>Sedentary behaviors such as watching television, playing computer games, playing video games or phone games, and surfing the Internet will be self-reported by the children using validated questionnaires</description>
  </other_outcome>
  <other_outcome>
    <measure>Confounding variable: Socio-demographic variables:</measure>
    <time_frame>Baseline</time_frame>
    <description>Information about socioeconomic status, demographic characteristics and family medical history of obesity, diabetes, dyslipidemia and hypertension will be collected. Socioeconomic status will be evaluated using The Family Affluence Scale (74) and parental education level and parental occupation. As demographic characteristics date of birth, sex, ethnicity and family structure will be recorded.</description>
  </other_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">84</enrollment>
  <condition>Overweight Children With Type 2 Diabetes Risk</condition>
  <arm_group>
    <arm_group_label>Control group</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Family-based lifestyle education and psycho-educational program</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Exercise group</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Supervised exercise plus family-based lifestyle education and psycho-educational program</description>
  </arm_group>
  <intervention>
    <intervention_type>Behavioral</intervention_type>
    <intervention_name>lifestyle and psycho-educational program</intervention_name>
    <description>The family-based healthy lifestyle education and psychological education program will be followed once every two weeks (11 sessions over 22 weeks) for 90 minutes (45 minutes in the healthy lifestyle education program and 45 minutes in the psycho-educational intervention). The sessions of the healthy lifestyle education and psycho-educational interventions will be developed simultaneously and delivered to both parents (or caregivers) and children, separately. The family-based healthy lifestyle education program will be conducted by experienced nutritionists and the psycho-educational program by experienced psychologists in behavior changes</description>
    <arm_group_label>Control group</arm_group_label>
    <arm_group_label>Exercise group</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Exercise plus lifestyle and psycho-educational program</intervention_name>
    <description>The intervention group will attend the same lifestyle education and psycho-educational program plus the exercise program. The exercise group will do exercise 3 days/week, 90 minutes per session, over a 22-week period. The program will be offered to the families five days per week to choose a total of three days/week. Sessions will be designed and supervised by exercise specialists. The duration of training sessions will be 90 minutes of exercise, including warm-up, moderate to vigorous aerobic activities, and strength exercises</description>
    <arm_group_label>Exercise group</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Overweight/obese children aged between 8 and 12 years, meeting the international&#xD;
             criteria for classification for T2D risk and having at least one parent or caregiver&#xD;
             willing to participate in the program sessions will be included&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Children with any medical condition that could affect the results of the study or that&#xD;
             limits physical activity will be excluded&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>8 Years</minimum_age>
    <maximum_age>12 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Pediatric Endocrinology Unit of the University Hospital of Araba (HUA)</name>
      <address>
        <city>Vitoria-Gasteiz</city>
        <state>Araba</state>
        <zip>01009</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Spain</country>
  </location_countries>
  <reference>
    <citation>Medrano M, Maiz E, Maldonado-Martin S, Arenaza L, Rodriguez-Vigil B, Ortega FB, Ruiz JR, Larrarte E, Diez-Lopez I, Sarasua-Miranda A, Tobalina I, Barrenechea L, Perez-Asenjo J, Kannengiesser S, Manhaes-Savio A, Echaniz O, Labayen I. The effect of a multidisciplinary intervention program on hepatic adiposity in overweight-obese children: protocol of the EFIGRO study. Contemp Clin Trials. 2015 Nov;45(Pt B):346-355. doi: 10.1016/j.cct.2015.09.017. Epub 2015 Sep 25.</citation>
    <PMID>26408054</PMID>
  </reference>
  <verification_date>November 2020</verification_date>
  <study_first_submitted>January 16, 2017</study_first_submitted>
  <study_first_submitted_qc>January 18, 2017</study_first_submitted_qc>
  <study_first_posted type="Estimate">January 23, 2017</study_first_posted>
  <last_update_submitted>November 19, 2020</last_update_submitted>
  <last_update_submitted_qc>November 19, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">November 20, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>University of the Basque Country (UPV/EHU)</investigator_affiliation>
    <investigator_full_name>IDOIA LABAYEN</investigator_full_name>
    <investigator_title>Professor</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Diabetes Mellitus</mesh_term>
    <mesh_term>Overweight</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/NCT03027726
org study id: DEP2016-78377-R
nct id: NCT03027726
lead sponsor: 
collaborator: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
Background: The global pandemic obesity has led to increased risk for prediabetes and type 2
      diabetes (T2D).

      Objectives: (i) To evaluate the effect of a 22 weeks multidisciplinary intervention program
      including exercise on T2D risk in pre-adolescents with high risk to develop T2D, and (ii) To
      identify the profile of microRNA in circulating exosomes and in blood peripheral mononuclear
      cells in pre-adolescents with high risk to develop T2D and its response to a
      multidisciplinary intervention program including exercise.
Background: The global pandemic obesity has led to increased risk for prediabetes and type 2
      diabetes (T2D).

      Objectives: (i) To evaluate the effect of a 22 weeks multidisciplinary intervention program
      including exercise on T2D risk in pre-adolescents with high risk to develop T2D, and (ii) To
      identify the profile of microRNA in circulating exosomes and in blood peripheral mononuclear
      cells in pre-adolescents with high risk to develop T2D and its response to a
      multidisciplinary intervention program including exercise.

      Design, participants and methods: A total of 84 children with high risk of type 2 diabetes
      mellitus aged 8-12 years will be included and randomly assigned to control (N=42) or
      intervention (N=42) groups. The control group will receive a family-based lifestyle education
      and psycho-educational program (2 days/month), while the intervention group will attend the
      same lifestyle education and psycho-educational program plus the exercise program (3
      days/week). The duration of training sessions will be 90 min of exercise, including warm-up,
      moderate to vigorous aerobic activities, and strength exercises. The following measurements
      will be evaluated at baseline prior to randomization and after the intervention: fasting,
      insulin glucose, and hemoglobin A1c; total and abdominal fat (dual X-ray absorptiometry);
      pancreatic, hepatic and visceral fat (magnetic resonance imaging); systolic and diastolic
      blood pressure; fasting leptin, adiponectin, fibroblast growth factor-21, fetuin-A,
      hs-C-reactive protein, tumor necrosis factor-alfa, interleukin (IL)-1beta and IL-6 and lipid
      profile; carotid intima-media thickness (ultrasonography), microRNA expression in circulating
      exosomes and in blood peripheral mononuclear cells (MiSeq-Illumina); functional peak aerobic
      capacity (cardiopulmonary exercise testing and 20m shuttle run test). Changes in dietary
      habits (food frequency questionnaire and two non-consecutive 24h recalls), physical activity
      and sleep (accelerometry); sex, age, socioeconomic status and pubertal status will be used as
      potential confounders.

      Discussion/Conclusions: Early prevention and identification of children with high risk to
      develop T2D could help to reduce the morbidity and mortality associated with the disease.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Insulin resistance
time frame: Baseline and at the end of the 22 weeks of intervention
description: The Homeostasis model assessment index will be calculated as fasting insulin concentration (microU/mL) x fasting glucose concentration (mmol/L)/22.5.
measure: microRNA expression in circulating exosomes and in blood peripheral mononuclear cells
time frame: Baseline and at the end of the 22 weeks of intervention
description: The expression of miRNAs will be measured in circulating exosomes and in white blood cells (MiSeq-Ilumina)
measure: Ectopic fat: pancreatic and liver fat accumulation
time frame: Baseline and at the end of the 22 weeks of intervention
description: Hepatic and pancreatic fat will be measured by magnetic resonance
measure: Total, abdominal and visceral adiposity
time frame: Baseline and at the end of the 22 weeks of intervention
description: Total and abdominal adiposity will be measured by dual energy X-ray absorptiometry. Visceral adiposity will be measured by magnetic resonance imaging
measure: Anthropometry and blood pressure
time frame: Baseline and at the end of the 22 weeks of intervention
description: Body mass, height and waist circumference will be measured following standard protocols at least twice until consistent measures will be obtained and thereafter, body mass index (BMI) and waist to height ratio will be calculated. Systolic and diastolic blood pressure measurements will be performed following the recommendations for children using an arm blood pressure oscillometric monitor device
measure: Cardiorespiratory fitness
time frame: Baseline and at the end of the 22 weeks of intervention
description: Cardiorespiratory fitness will be assessed by two different tests: (i) The 20m shuttle run test in which the equation reported by Léger et al. will be used to estimate the maximum oxygen consumption (VO2max, ml/kg/min) from the 20m shuttle run test scores, and (ii) Direct cardiopulmonary exercise progressive incremental treadmill test using the modified American College of Sports Medicine protocol with respiratory gas analysis to exhaustion
measure: Carotid intima-media thickness
time frame: Baseline and at the end of the 22 weeks of intervention
description: carotid intima-media thickness will be measured by ultrasound according to international recommendations.
measure: Inflammation and biochemical cardiovascular disease risk factors
time frame: Baseline and at the end of the 22 weeks of intervention
description: Fasting lipid profile (total-, HDL- and LDL-cholesterol, and triglycerides), glucose, insulin, and hemoglobin A1c, cytokines (e.g. tumor necrosis factor alpha and IL-6) adipokines (e.g leptin and adiponectin), hepatokines (fetuin-A and fibroblast growth factor-21), liver enzymes (alanine aminotransferase, aspartate aminotransferase and gamma-glutamyl transferase), C-reactive protein, thyroid hormones (thyroid stimulating hormone, triiodothyronine and free thyroxine), urea, bilirubin and uric acid
measure: Confounding variable: puberty stage
time frame: Baseline
description: The pediatrician will evaluate Tanner staging by direct examination with breast palpation in girls and testicular measurement by orchidometer in boys.
measure: Confounding variable:physical activity and sleep
time frame: Baseline and at the end of the 22 weeks of intervention
description: Children will wear an activity monitor on the wrist for 7 consecutive days for 24 hours to record physical activity intensity levels and patterns, as well as sleeping habits and participants will also complete a diary log
measure: Confounding variable: dietary habits
time frame: Baseline and at the end of the 22 weeks of intervention
description: Dietary intake will be evaluated by two non-consecutive 24h recalls within a period of seven days by nutritionists and a validated food frequency questionnaire
measure: Confounding variable: sedentary behaviors
time frame: Baseline and at the end of the 22 weeks of intervention
description: Sedentary behaviors such as watching television, playing computer games, playing video games or phone games, and surfing the Internet will be self-reported by the children using validated questionnaires
measure: Confounding variable: Socio-demographic variables:
time frame: Baseline
description: Information about socioeconomic status, demographic characteristics and family medical history of obesity, diabetes, dyslipidemia and hypertension will be collected. Socioeconomic status will be evaluated using The Family Affluence Scale (74) and parental education level and parental occupation. As demographic characteristics date of birth, sex, ethnicity and family structure will be recorded.
arm group label: Control group
arm group type: Active Comparator
description: Family-based lifestyle education and psycho-educational program
arm group label: Exercise group
arm group type: Experimental
description: Supervised exercise plus family-based lifestyle education and psycho-educational program
intervention type: Behavioral
intervention name: lifestyle and psycho-educational program
description: The family-based healthy lifestyle education and psychological education program will be followed once every two weeks (11 sessions over 22 weeks) for 90 minutes (45 minutes in the healthy lifestyle education program and 45 minutes in the psycho-educational intervention). The sessions of the healthy lifestyle education and psycho-educational interventions will be developed simultaneously and delivered to both parents (or caregivers) and children, separately. The family-based healthy lifestyle education program will be conducted by experienced nutritionists and the psycho-educational program by experienced psychologists in behavior changes
arm group label: Control group
arm group label: Exercise group
intervention type: Other
intervention name: Exercise plus lifestyle and psycho-educational program
description: The intervention group will attend the same lifestyle education and psycho-educational program plus the exercise program. The exercise group will do exercise 3 days/week, 90 minutes per session, over a 22-week period. The program will be offered to the families five days per week to choose a total of three days/week. Sessions will be designed and supervised by exercise specialists. The duration of training sessions will be 90 minutes of exercise, including warm-up, moderate to vigorous aerobic activities, and strength exercises
arm group label: Exercise group
criteria: 
gender: All
minimum age: 8 Years
maximum age: 12 Years
healthy volunteers: No
facility: 
country: Spain
citation: Medrano M, Maiz E, Maldonado-Martin S, Arenaza L, Rodriguez-Vigil B, Ortega FB, Ruiz JR, Larrarte E, Diez-Lopez I, Sarasua-Miranda A, Tobalina I, Barrenechea L, Perez-Asenjo J, Kannengiesser S, Manhaes-Savio A, Echaniz O, Labayen I. The effect of a multidisciplinary intervention program on hepatic adiposity in overweight-obese children: protocol of the EFIGRO study. Contemp Clin Trials. 2015 Nov;45(Pt B):346-355. doi: 10.1016/j.cct.2015.09.017. Epub 2015 Sep 25.
PMID: 26408054
responsible party type: Principal Investigator
investigator affiliation: University of the Basque Country (UPV/EHU)
investigator full name: IDOIA LABAYEN
investigator title: Professor
mesh term: Diabetes Mellitus
mesh term: Overweight