<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/NCT03813381</url>
  </required_header>
  <id_info>
    <org_study_id>CARE-PRO</org_study_id>
    <nct_id>NCT03813381</nct_id>
  </id_info>
  <brief_title>CAlorie and Protein REstriction PROgram in Barrett's Esophagus Patients (CARE-PRO).</brief_title>
  <acronym>CARE-PRO</acronym>
  <official_title>The Impact of a Moderate CAlorie and Protein REstriction PROgram (CARE-PRO) as an Efficient and Affordable Therapeutic Strategy in Patients With Barrett's Esophagus.</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Istituto Oncologico Veneto IRCCS</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Istituto Oncologico Veneto IRCCS</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>
      The increasing incidence of Esophageal Adenocarcinoma (EAC) in several Western countries can&#xD;
      be primarily ascribed to risk factors such as obesity, chronic gastroesophageal reflux,&#xD;
      dietary habits and alcohol intake. Nevertheless, Barrett's Esophagus (BE), remains the main&#xD;
      risk factor for EAC. Several studies supports the role played by the gut microbiota on the&#xD;
      modulation of metabolic and immunological pathways. An abnormal state of the microbial&#xD;
      ecosystem seems to be involved in the promotion and onset of various diseases, including&#xD;
      cancer. Recent studies have shown that diet and lifestyle have an important modulatory role&#xD;
      as protective or risk factors for oncological diseases. The World Cancer Research Fund (WCRF)&#xD;
      and the American Institute for Cancer Research (AICR) released a review of the evidence that&#xD;
      emerged from published studies in the field of nutrition and cancer prevention and summarized&#xD;
      their findings into 10 recommendations. Several studies have also shown that a moderate&#xD;
      caloric and/or protein restriction seems to be able to reduce the risk of neoplastic disease&#xD;
      development. The primary aim of this study is to evaluate the impact of a lifestyle-oriented&#xD;
      intervention on body weight, waist circumference, biomarkers associated with cancer risk,&#xD;
      esophageal microbiota composition and adherence to cancer prevention recommendations after 24&#xD;
      months in overweight or obese BE patients.&#xD;
&#xD;
      Methods and analysis: Patients are randomly divided into two arms, a control arm (CA) and an&#xD;
      interventional arm (IA). The CA receives information about a correct lifestyle to prevent&#xD;
      cancer.&#xD;
&#xD;
      The IA is involved in the two-year program of moderate caloric and protein restriction.&#xD;
&#xD;
      At the time of enrollment, anthropometric measurements will be recorded for each patient and&#xD;
      they will be randomized to IA or CA. Blood samples will be obtained from each patient and&#xD;
      blood glucose will be determined. Serum metabolic biomarkers will be measured in each serum&#xD;
      sample and total proteins will be extracted from fresh frozen esophageal biopsy and will be&#xD;
      analyzed to evaluate the insulin signal pathway.&#xD;
&#xD;
      To assess esophageal microbiota profiling, total genomic DNA (gDNA) will be extracted from&#xD;
      matched fresh frozen biopsy.&#xD;
&#xD;
      In order to determine a score of adherence to cancer prevention recommendations, participants&#xD;
      will be asked to complete a self-administrated questionnaire reflecting WCRF/AICR&#xD;
      recommendations.&#xD;
&#xD;
      All the measurements will also occur at the end point, after two years from the enrollment.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Enrolling by invitation</last_known_status>
  <start_date type="Actual">November 25, 2015</start_date>
  <completion_date type="Anticipated">December 31, 2020</completion_date>
  <primary_completion_date type="Anticipated">December 31, 2020</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>Body weight change</measure>
    <time_frame>Baseline and after 24 months</time_frame>
    <description>A 7% weight loss</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Metabolic serum biomarkers</measure>
    <time_frame>Baseline and after 24 months</time_frame>
    <description>Fasting glucose (mg/dl)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Metabolic serum biomarkers</measure>
    <time_frame>Baseline and after 24 months</time_frame>
    <description>Insulin (pg/ml) and C-peptide (pg/ml), tumor necrosis factor-alpha -TNF-alpha (pg/ml) and Interleukin-6 - IL-6 (pg/ml).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Metabolic serum biomarkers</measure>
    <time_frame>Baseline and after 24 months</time_frame>
    <description>Insulin-like growth factor - IGF1 (nmol/ml), insulin-like growth factor binding protein 1 and 3 - IGFBP1 (nmol/ml) and IGFBP3 (nmol/ml)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Metabolic serum biomarkers</measure>
    <time_frame>Baseline and after 24 months</time_frame>
    <description>Leptin (ng/ml)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Metabolic serum biomarkers</measure>
    <time_frame>Baseline and after 24 months</time_frame>
    <description>Adiponectin (µg/ml)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Insulin resistance index (HOMA-IR)</measure>
    <time_frame>Baseline and after 24 months</time_frame>
    <description>HOMA-IR index [fasting plasma glucose (mg/dl) × fasting serum insulin(μU/ml)/405]</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Expression of proteins involved on insulin and IGF1 receptors signal transduction</measure>
    <time_frame>Baseline and after 24 months</time_frame>
    <description>Phosphoinositide 3-kinases (PI3K)/Protein kinase B(Akt) pathway; mitogenic (ERK/MAPK) pathway</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Esophageal microbiota composition</measure>
    <time_frame>Baseline and after 24 months</time_frame>
    <description>To assess esophageal microbiota profiling, total gDNA will be extracted from fresh frozen biopsy. Specific primers for the bacterial V3-V4 hypervariable regions of 16S ribosomal ribonucleic acid (rRNA) will be used to amplify bacterial DNA [≈ 500 bases pair (bp)] to be sequenced by Illumina Miseq platform with 300 bp paired-end approach.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Adherence score to World Cancer Research Fund and the American Institute for Cancer Research (WCRF/AICR) recommendations for cancer prevention.</measure>
    <time_frame>Baseline and after 24 months</time_frame>
    <description>In order to determine a score of adherence to cancer prevention recommendations, participants will be asked to complete a 6-item self-administrated questionnaire reflecting six recommendations provided by the World Cancer Research Fund and the American Institute for Cancer Research (WCRF/AICR).&#xD;
A score of 1 will be assigned when the item is met and a score of 0 will be assigned when it is not. An answer that partially satisfies the item will be assigned a score of 0.5. Some recommendation (item) have sub-item (item 3,4 and 5). Even for sub-item the score will be 1-0 with 0.5 for partially satisfied item. For total score of item presenting sub-item, we will consider the score obtained by calculating the average score between the sub-item.&#xD;
The final adherence score will derive from the mathematical sum of the individual scores obtained for each item. The maximum expected score will be equal to 6 (full adherence).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Waist circumference reduction</measure>
    <time_frame>Baseline and after 24 months</time_frame>
    <description>Waist circumference (cm)</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">190</enrollment>
  <condition>Barrett's Esophagus</condition>
  <condition>Overweight and Obesity</condition>
  <arm_group>
    <arm_group_label>Intervention Arm (IA)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients randomized in the Intervention Arm (IA) will be given personalized diet based on calorie and protein restriction. Calorie restriction will be up to 600 kcal below patients' energy requirements and the amount of protein will be 0.8g of protein/Kg body weight mostly form plant-origin food.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Control Arm (CA)</arm_group_label>
    <arm_group_type>No Intervention</arm_group_type>
    <description>Participants in the CA will be given information about the importance of a healthy lifestyle in reducing the risk of cancer and will receive a leaflet based on WCRF/AICR recommendations.</description>
  </arm_group>
  <intervention>
    <intervention_type>Behavioral</intervention_type>
    <intervention_name>Calorie and protein restriction diet</intervention_name>
    <description>Patient in intervention arm will be given individualized dietary advice on the basis of WCRF/AICR recommendations. The aim of healthy dietary advice will be the reduction of patient's total daily calorie intake up to 600 kcal below their energy requirements and 0.8g of protein/Kg body weight mostly form plant-origin food.&#xD;
Patients, periodically, will meet the dietitian for a 45-minute nutritional counselling session and a trained nurse for a 15-minute health coaching session.&#xD;
Each patient in the IA will be involved in at least three 4-hour cooking classes.&#xD;
Patients in the IA, after a medical/cardiac evaluation to assure their physical ability for exercise, will attend Nordic walking sessions of moderate intensity two times per month during the 24 months of intervention.</description>
    <arm_group_label>Intervention Arm (IA)</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Histological confirmation of Barrett's esophagus without dysplasia or cancer aged ≥ 18&#xD;
             years with BMI ≥ 25.0 kg/m^2&#xD;
&#xD;
          -  Willingness and ability to perform supervised Nordic walking session twice a month and&#xD;
             self-planned physical activity at least 3 times a week&#xD;
&#xD;
          -  Signed informed consent&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  No histological confirmation of Barrett's esophagus&#xD;
&#xD;
          -  Cancer diagnosis within one year before trial begins&#xD;
&#xD;
          -  Presence of insulin-dependent diabetes&#xD;
&#xD;
          -  Denied informed consent&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Stefano Realdon, MD, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Veneto Institute of Oncology IOV-IRCCS, Padua, Italy</affiliation>
  </overall_official>
  <link>
    <url>http://wcrf.org/oesophageal-cancer-2016</url>
    <description>Related Info</description>
  </link>
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  <verification_date>January 2019</verification_date>
  <study_first_submitted>January 9, 2019</study_first_submitted>
  <study_first_submitted_qc>January 20, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">January 23, 2019</study_first_posted>
  <last_update_submitted>January 20, 2019</last_update_submitted>
  <last_update_submitted_qc>January 20, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">January 23, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Istituto Oncologico Veneto IRCCS</investigator_affiliation>
    <investigator_full_name>Stefano Realdon</investigator_full_name>
    <investigator_title>Head of Digestive Endoscopy Unit</investigator_title>
  </responsible_party>
  <keyword>Esophageal adenocarcinoma</keyword>
  <keyword>Diet</keyword>
  <keyword>Physical activity</keyword>
  <keyword>Microbiota</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Barrett Esophagus</mesh_term>
    <mesh_term>Overweight</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>Undecided</sharing_ipd>
  </patient_data>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol and Statistical Analysis Plan</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>November 11, 2014</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/81/NCT03813381/Prot_SAP_000.pdf</document_url>
    </provided_document>
  </provided_document_section>
  <!-- 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/NCT03813381
org study id: CARE-PRO
nct id: NCT03813381
lead sponsor: 
is fda regulated drug: No
is fda regulated device: No
The increasing incidence of Esophageal Adenocarcinoma (EAC) in several Western countries can
      be primarily ascribed to risk factors such as obesity, chronic gastroesophageal reflux,
      dietary habits and alcohol intake. Nevertheless, Barrett's Esophagus (BE), remains the main
      risk factor for EAC. Several studies supports the role played by the gut microbiota on the
      modulation of metabolic and immunological pathways. An abnormal state of the microbial
      ecosystem seems to be involved in the promotion and onset of various diseases, including
      cancer. Recent studies have shown that diet and lifestyle have an important modulatory role
      as protective or risk factors for oncological diseases. The World Cancer Research Fund (WCRF)
      and the American Institute for Cancer Research (AICR) released a review of the evidence that
      emerged from published studies in the field of nutrition and cancer prevention and summarized
      their findings into 10 recommendations. Several studies have also shown that a moderate
      caloric and/or protein restriction seems to be able to reduce the risk of neoplastic disease
      development. The primary aim of this study is to evaluate the impact of a lifestyle-oriented
      intervention on body weight, waist circumference, biomarkers associated with cancer risk,
      esophageal microbiota composition and adherence to cancer prevention recommendations after 24
      months in overweight or obese BE patients.

      Methods and analysis: Patients are randomly divided into two arms, a control arm (CA) and an
      interventional arm (IA). The CA receives information about a correct lifestyle to prevent
      cancer.

      The IA is involved in the two-year program of moderate caloric and protein restriction.

      At the time of enrollment, anthropometric measurements will be recorded for each patient and
      they will be randomized to IA or CA. Blood samples will be obtained from each patient and
      blood glucose will be determined. Serum metabolic biomarkers will be measured in each serum
      sample and total proteins will be extracted from fresh frozen esophageal biopsy and will be
      analyzed to evaluate the insulin signal pathway.

      To assess esophageal microbiota profiling, total genomic DNA (gDNA) will be extracted from
      matched fresh frozen biopsy.

      In order to determine a score of adherence to cancer prevention recommendations, participants
      will be asked to complete a self-administrated questionnaire reflecting WCRF/AICR
      recommendations.

      All the measurements will also occur at the end point, after two years from the enrollment.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Body weight change
time frame: Baseline and after 24 months
description: A 7% weight loss
measure: Metabolic serum biomarkers
time frame: Baseline and after 24 months
description: Fasting glucose (mg/dl)
measure: Metabolic serum biomarkers
time frame: Baseline and after 24 months
description: Insulin (pg/ml) and C-peptide (pg/ml), tumor necrosis factor-alpha -TNF-alpha (pg/ml) and Interleukin-6 - IL-6 (pg/ml).
measure: Metabolic serum biomarkers
time frame: Baseline and after 24 months
description: Insulin-like growth factor - IGF1 (nmol/ml), insulin-like growth factor binding protein 1 and 3 - IGFBP1 (nmol/ml) and IGFBP3 (nmol/ml)
measure: Metabolic serum biomarkers
time frame: Baseline and after 24 months
description: Leptin (ng/ml)
measure: Metabolic serum biomarkers
time frame: Baseline and after 24 months
description: Adiponectin (µg/ml)
measure: Insulin resistance index (HOMA-IR)
time frame: Baseline and after 24 months
description: HOMA-IR index [fasting plasma glucose (mg/dl) × fasting serum insulin(μU/ml)/405]
measure: Expression of proteins involved on insulin and IGF1 receptors signal transduction
time frame: Baseline and after 24 months
description: Phosphoinositide 3-kinases (PI3K)/Protein kinase B(Akt) pathway; mitogenic (ERK/MAPK) pathway
measure: Esophageal microbiota composition
time frame: Baseline and after 24 months
description: To assess esophageal microbiota profiling, total gDNA will be extracted from fresh frozen biopsy. Specific primers for the bacterial V3-V4 hypervariable regions of 16S ribosomal ribonucleic acid (rRNA) will be used to amplify bacterial DNA [≈ 500 bases pair (bp)] to be sequenced by Illumina Miseq platform with 300 bp paired-end approach.
measure: Adherence score to World Cancer Research Fund and the American Institute for Cancer Research (WCRF/AICR) recommendations for cancer prevention.
time frame: Baseline and after 24 months
description: In order to determine a score of adherence to cancer prevention recommendations, participants will be asked to complete a 6-item self-administrated questionnaire reflecting six recommendations provided by the World Cancer Research Fund and the American Institute for Cancer Research (WCRF/AICR).
A score of 1 will be assigned when the item is met and a score of 0 will be assigned when it is not. An answer that partially satisfies the item will be assigned a score of 0.5. Some recommendation (item) have sub-item (item 3,4 and 5). Even for sub-item the score will be 1-0 with 0.5 for partially satisfied item. For total score of item presenting sub-item, we will consider the score obtained by calculating the average score between the sub-item.
The final adherence score will derive from the mathematical sum of the individual scores obtained for each item. The maximum expected score will be equal to 6 (full adherence).
measure: Waist circumference reduction
time frame: Baseline and after 24 months
description: Waist circumference (cm)
arm group label: Intervention Arm (IA)
arm group type: Experimental
description: Patients randomized in the Intervention Arm (IA) will be given personalized diet based on calorie and protein restriction. Calorie restriction will be up to 600 kcal below patients' energy requirements and the amount of protein will be 0.8g of protein/Kg body weight mostly form plant-origin food.
arm group label: Control Arm (CA)
arm group type: No Intervention
description: Participants in the CA will be given information about the importance of a healthy lifestyle in reducing the risk of cancer and will receive a leaflet based on WCRF/AICR recommendations.
intervention type: Behavioral
intervention name: Calorie and protein restriction diet
description: Patient in intervention arm will be given individualized dietary advice on the basis of WCRF/AICR recommendations. The aim of healthy dietary advice will be the reduction of patient's total daily calorie intake up to 600 kcal below their energy requirements and 0.8g of protein/Kg body weight mostly form plant-origin food.
Patients, periodically, will meet the dietitian for a 45-minute nutritional counselling session and a trained nurse for a 15-minute health coaching session.
Each patient in the IA will be involved in at least three 4-hour cooking classes.
Patients in the IA, after a medical/cardiac evaluation to assure their physical ability for exercise, will attend Nordic walking sessions of moderate intensity two times per month during the 24 months of intervention.
arm group label: Intervention Arm (IA)
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Stefano Realdon, MD, PhD
role: Principal Investigator
affiliation: Veneto Institute of Oncology IOV-IRCCS, Padua, Italy
url: http://wcrf.org/oesophageal-cancer-2016
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responsible party type: Principal Investigator
investigator affiliation: Istituto Oncologico Veneto IRCCS
investigator full name: Stefano Realdon
investigator title: Head of Digestive Endoscopy Unit
mesh term: Barrett Esophagus
mesh term: Overweight
sharing ipd: Undecided
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