<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/NCT03285230</url>
  </required_header>
  <id_info>
    <org_study_id>C 95-01</org_study_id>
    <nct_id>NCT03285230</nct_id>
  </id_info>
  <brief_title>The French E3N Prospective Cohort Study</brief_title>
  <acronym>E3N</acronym>
  <official_title>The French E3N Prospective Cohort Study (Etude Epidémiologique auprès de Femmes de la Mutuelle Générale de l'Education Nationale)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Institut National de la Santé Et de la Recherche Médicale, France</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Université Paris-Sud</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Gustave Roussy, Cancer Campus, Grand Paris</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Ligue contre le cancer, France</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Institut National de la Santé Et de la Recherche Médicale, France</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The French E3N cohort was initiated in 1990 to investigate the risk factors associated with&#xD;
      cancer and other major non-communicable diseases in women.&#xD;
&#xD;
      The participants were insured through a national health system that primarily covered&#xD;
      teachers, and were enrolled from 1990 after returning baseline self-administered&#xD;
      questionnaires and providing informed consent. The cohort comprised nearly 100 000 women with&#xD;
      baseline ages ranging from 40 to 65 years.&#xD;
&#xD;
      Follow-up questionnaires were sent approximately every 2-3 years after the baseline and&#xD;
      addressed general and lifestyle characteristics together with medical events (cancer,&#xD;
      cardiovascular diseases, diabetes, depression, fractures and asthma, among others). The&#xD;
      follow-up questionnaire response rate remained stable at approximately 80%.&#xD;
&#xD;
      A biological material bank was generated and included blood samples collected from 25 000&#xD;
      women and saliva samples from an additional 47 000 women.&#xD;
&#xD;
      Ageing among the E3N cohort provided the opportunity to investigate factors related to&#xD;
      agerelated diseases and conditions as well as disease survival.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Who is in the cohort? In June 1990, a questionnaire was sent to 500 000 women who had been&#xD;
      born between 1925 and 1950 and were insured by the Mutuelle Générale de l'Education Nationale&#xD;
      (MGEN), a national health insurance plan that primarily covers teachers. The questionnaire&#xD;
      was sent along with a leaflet explaining that an Inserm research team was launching a study&#xD;
      of cancer risk factors and that participation would require filling in questionnaires every&#xD;
      2-3 years as well as the submission of a signed consent form providing permission to obtain&#xD;
      information about each participant's vital status, address changes and medical expense&#xD;
      reimbursements from the insurance plan. Nearly 100 000 women volunteered.&#xD;
&#xD;
      How often have they been followed-up? Until now, nine follow-up questionnaires have been sent&#xD;
      every 2-3 years from the baseline. Approximately half of the answers were obtained after the&#xD;
      first mailing. Two reminders were sent thereafter. The questionnaires were accompanied with&#xD;
      newsletters that informed participants about the major results obtained to date. The&#xD;
      participation rate remained high (77-92% according to the questionnaires) and the lost to&#xD;
      follow-up rate was minimal because of the ability to trace non-respondents through their&#xD;
      insurance plan files. The questionnaires were accurately filled in, with few missing or&#xD;
      unacceptable answers.&#xD;
&#xD;
      What has been measured? To date, 11 self-administered questionnaires have been sent. The&#xD;
      collected data are sociodemographic factors, anthropometric measurements, reproductive&#xD;
      factors, hormonal treatments, health behaviour and lifestyle. Each follow-up questionnaire&#xD;
      also recorded the participant's health status. The questionnaires are available at www.e3n.fr&#xD;
      .&#xD;
&#xD;
      The questionnaires are anonymous and identified with an identification number and pin code&#xD;
      that can be rapidly scanned to identify the respondents. The questionnaires are optically&#xD;
      scanned and all answers are checked on screen. The scanned images are saved to allow data&#xD;
      entry at a later time, including information regarding the addresses of medical doctors (18&#xD;
      000 to date) or drug names (pre-listed to avoid errors). The longitudinal data (repeats of&#xD;
      identical questions for the purpose of updating information about topics such as menopause or&#xD;
      smoking) are routinely homogenized. Several validation studies (e.g. dietary and&#xD;
      anthropometrical data studies) have been performed and have revealed very satisfactory&#xD;
      results.&#xD;
&#xD;
      Self-reported cases of cancer are validated and coded after reviewing the pathology reports&#xD;
      obtained from medical practitioners, and nearly 90% of all cancer cases are histologically&#xD;
      confirmed. Other diseases are also validated (e.g. diabetes, myocardial infarction, stroke,&#xD;
      Parkinson disease) by requesting additional information about the participants (e.g.&#xD;
      glycosylated haemoglobin levels, fracture-related circumstances, drug names) and sending&#xD;
      questionnaires to medical doctors.&#xD;
&#xD;
      Additionally, a biological material bank was generated. Blood samples were initially&#xD;
      collected from 1994-99. The participation rate among the invited participants was&#xD;
      approximately 40%; this yielded approximately 25 000 blood samples that were each separated&#xD;
      into 28 aliquots (e.g. plasma, serum, leukocytes, erythrocytes). Plastic straws were used to&#xD;
      store each participant's samples in liquid nitrogen containers. The bio-repositories are&#xD;
      located at the IARC (Lyon) and the EFS (Etablissement Français du Sang, Annemasse). Since&#xD;
      2004, approximately 10 case-control studies have been conducted (approximately 1 800 cases&#xD;
      and 3 500 controls) with regard to the measurements of various biomarkers (e.g. fatty acids,&#xD;
      calcium, vitamin D, vitamin B, cholesterol and C-reactive protein). A metabolomics study is&#xD;
      currently ongoing.&#xD;
&#xD;
      From 2009-11, saliva samples (Oragene, DNA Genotek, Kanata, ON, Canada) were requested from&#xD;
      68 242 living women and were obtained from 47 000 women (participation rate, 69%). Salivary&#xD;
      DNA has been extracted and has been used for genotyping in two case-control studies&#xD;
      (approximately 2 500 cases and 850 controls) since December 2010.&#xD;
&#xD;
      The research team is currently planning to set up a tumour tissue bank and will begin with&#xD;
      the collection of breast cancer tissues.&#xD;
&#xD;
      What has it found? The E3N cohort has produced a spectrum of results regarding the complex&#xD;
      roles played by nutrition, hormonal factors, physical activity, anthropometric&#xD;
      characteristics and other major lifestyle-related factors with respect to various diseases.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">June 15, 1990</start_date>
  <completion_date type="Anticipated">December 15, 2025</completion_date>
  <primary_completion_date type="Actual">November 15, 1991</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Cohort</observational_model>
    <time_perspective>Prospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>Anthropometric measurements</measure>
    <time_frame>From 1990 until now</time_frame>
    <description>Height, weight, hip circumference and waist circumference</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Educational level</measure>
    <time_frame>1990</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Professional activity</measure>
    <time_frame>1992 and 2005</time_frame>
    <description>Insee categories</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Age at cessation of activity</measure>
    <time_frame>From 2005 until now</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Menstrual factors</measure>
    <time_frame>From 1990 to 2002</time_frame>
    <description>Age at menarche, length of menstrual cycle</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Reproductive history</measure>
    <time_frame>From 1990 to 1992</time_frame>
    <description>Number of pregnancies, age at each pregnancy, durations and outcomes of pregnancies, breastfeeding, infertility</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Menopause</measure>
    <time_frame>1990, 1995, 1997, 2000, 2002, 2005</time_frame>
    <description>Age, type</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Hormonal Treatments</measure>
    <time_frame>From 1992 to 2008</time_frame>
    <description>Menopausal Hormonal Treatments (MHT), oral contraceptives</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Tobacco consumption</measure>
    <time_frame>From 1990 until now</time_frame>
    <description>Type, quantity, time of smoking</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Alcohol consumption</measure>
    <time_frame>1993, 1997, 2005</time_frame>
    <description>Type of alcohol, quantity</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Physical activity</measure>
    <time_frame>1990,1997,2002, 2005, 2014</time_frame>
    <description>Moderate and intense activity, sedentarity</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Diet questionnaire</measure>
    <time_frame>1993 and 2002</time_frame>
    <description>Precise annual diet questionnaire</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Family history of diseases</measure>
    <time_frame>1990 to 2005</time_frame>
    <description>Cancer, diabetes and cardiovascular diseases</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Medication use</measure>
    <time_frame>From 1990 until now</time_frame>
    <description>linked with the drug reimbursement files from the health insurance</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Medical and surgical history</measure>
    <time_frame>From 1990 until now</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Mental Health</measure>
    <time_frame>From 1990 until now</time_frame>
    <description>Centre for Epidemiologic Studies Depression Scale (CESD) and Depression</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Health outcomes</measure>
    <time_frame>From 1990 until now</time_frame>
  </primary_outcome>
  <enrollment type="Actual">100000</enrollment>
  <condition>Breast Cancer</condition>
  <condition>Colo-rectal Cancer</condition>
  <condition>Parkinson Disease</condition>
  <condition>Asthma</condition>
  <condition>Diabetes</condition>
  <condition>Inflammatory Bowel Diseases</condition>
  <condition>Melanoma</condition>
  <condition>Endometriosis</condition>
  <condition>Thyroid Cancer</condition>
  <condition>Hypertension</condition>
  <condition>Endometrial Cancer</condition>
  <condition>Crohn Disease</condition>
  <condition>Depression</condition>
  <condition>Cardiovascular Diseases</condition>
  <biospec_retention>Samples With DNA</biospec_retention>
  <biospec_descr>
    <textblock>
      25000 blood samples; 47000 saliva samples&#xD;
    </textblock>
  </biospec_descr>
  <eligibility>
    <study_pop>
      <textblock>
        The cohort comprised nearly 100 000 women with baseline ages ranging from 40 to 65 years,&#xD;
        all insured through a French national health system (MGEN).&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  only women&#xD;
&#xD;
          -  born between 1925 and 1950&#xD;
&#xD;
          -  insured by the Mutuelle Générale de l'Education Nationale (MGEN)&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
        - men&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <minimum_age>40 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Gianluca Severi, PhD</last_name>
    <role>Study Director</role>
    <affiliation>INSERM (Institut National de la Sante et de la Recherche Medicale)</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Marie-Christine Boutron-Ruault, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>INSERM (Institut National de la Sante et de la Recherche Medicale)</affiliation>
  </overall_official>
  <link>
    <url>http://www.e3n.fr</url>
    <description>website of the study</description>
  </link>
  <reference>
    <citation>Clavel-Chapelon F; E3N Study Group. Cohort Profile: The French E3N Cohort Study. Int J Epidemiol. 2015 Jun;44(3):801-9. doi: 10.1093/ije/dyu184. Epub 2014 Sep 10.</citation>
    <PMID>25212479</PMID>
  </reference>
  <verification_date>September 2017</verification_date>
  <study_first_submitted>July 27, 2017</study_first_submitted>
  <study_first_submitted_qc>September 12, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">September 15, 2017</study_first_posted>
  <last_update_submitted>September 18, 2017</last_update_submitted>
  <last_update_submitted_qc>September 18, 2017</last_update_submitted_qc>
  <last_update_posted type="Actual">September 19, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Endometrial Neoplasms</mesh_term>
    <mesh_term>Crohn Disease</mesh_term>
    <mesh_term>Inflammatory Bowel Diseases</mesh_term>
    <mesh_term>Parkinson Disease</mesh_term>
    <mesh_term>Endometriosis</mesh_term>
    <mesh_term>Cardiovascular Diseases</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/NCT03285230
org study id: C 95-01
nct id: NCT03285230
lead sponsor: 
collaborator: 
collaborator: 
collaborator: 
has dmc: Yes
The French E3N cohort was initiated in 1990 to investigate the risk factors associated with
      cancer and other major non-communicable diseases in women.

      The participants were insured through a national health system that primarily covered
      teachers, and were enrolled from 1990 after returning baseline self-administered
      questionnaires and providing informed consent. The cohort comprised nearly 100 000 women with
      baseline ages ranging from 40 to 65 years.

      Follow-up questionnaires were sent approximately every 2-3 years after the baseline and
      addressed general and lifestyle characteristics together with medical events (cancer,
      cardiovascular diseases, diabetes, depression, fractures and asthma, among others). The
      follow-up questionnaire response rate remained stable at approximately 80%.

      A biological material bank was generated and included blood samples collected from 25 000
      women and saliva samples from an additional 47 000 women.

      Ageing among the E3N cohort provided the opportunity to investigate factors related to
      agerelated diseases and conditions as well as disease survival.
Who is in the cohort? In June 1990, a questionnaire was sent to 500 000 women who had been
      born between 1925 and 1950 and were insured by the Mutuelle Générale de l'Education Nationale
      (MGEN), a national health insurance plan that primarily covers teachers. The questionnaire
      was sent along with a leaflet explaining that an Inserm research team was launching a study
      of cancer risk factors and that participation would require filling in questionnaires every
      2-3 years as well as the submission of a signed consent form providing permission to obtain
      information about each participant's vital status, address changes and medical expense
      reimbursements from the insurance plan. Nearly 100 000 women volunteered.

      How often have they been followed-up? Until now, nine follow-up questionnaires have been sent
      every 2-3 years from the baseline. Approximately half of the answers were obtained after the
      first mailing. Two reminders were sent thereafter. The questionnaires were accompanied with
      newsletters that informed participants about the major results obtained to date. The
      participation rate remained high (77-92% according to the questionnaires) and the lost to
      follow-up rate was minimal because of the ability to trace non-respondents through their
      insurance plan files. The questionnaires were accurately filled in, with few missing or
      unacceptable answers.

      What has been measured? To date, 11 self-administered questionnaires have been sent. The
      collected data are sociodemographic factors, anthropometric measurements, reproductive
      factors, hormonal treatments, health behaviour and lifestyle. Each follow-up questionnaire
      also recorded the participant's health status. The questionnaires are available at www.e3n.fr
      .

      The questionnaires are anonymous and identified with an identification number and pin code
      that can be rapidly scanned to identify the respondents. The questionnaires are optically
      scanned and all answers are checked on screen. The scanned images are saved to allow data
      entry at a later time, including information regarding the addresses of medical doctors (18
      000 to date) or drug names (pre-listed to avoid errors). The longitudinal data (repeats of
      identical questions for the purpose of updating information about topics such as menopause or
      smoking) are routinely homogenized. Several validation studies (e.g. dietary and
      anthropometrical data studies) have been performed and have revealed very satisfactory
      results.

      Self-reported cases of cancer are validated and coded after reviewing the pathology reports
      obtained from medical practitioners, and nearly 90% of all cancer cases are histologically
      confirmed. Other diseases are also validated (e.g. diabetes, myocardial infarction, stroke,
      Parkinson disease) by requesting additional information about the participants (e.g.
      glycosylated haemoglobin levels, fracture-related circumstances, drug names) and sending
      questionnaires to medical doctors.

      Additionally, a biological material bank was generated. Blood samples were initially
      collected from 1994-99. The participation rate among the invited participants was
      approximately 40%; this yielded approximately 25 000 blood samples that were each separated
      into 28 aliquots (e.g. plasma, serum, leukocytes, erythrocytes). Plastic straws were used to
      store each participant's samples in liquid nitrogen containers. The bio-repositories are
      located at the IARC (Lyon) and the EFS (Etablissement Français du Sang, Annemasse). Since
      2004, approximately 10 case-control studies have been conducted (approximately 1 800 cases
      and 3 500 controls) with regard to the measurements of various biomarkers (e.g. fatty acids,
      calcium, vitamin D, vitamin B, cholesterol and C-reactive protein). A metabolomics study is
      currently ongoing.

      From 2009-11, saliva samples (Oragene, DNA Genotek, Kanata, ON, Canada) were requested from
      68 242 living women and were obtained from 47 000 women (participation rate, 69%). Salivary
      DNA has been extracted and has been used for genotyping in two case-control studies
      (approximately 2 500 cases and 850 controls) since December 2010.

      The research team is currently planning to set up a tumour tissue bank and will begin with
      the collection of breast cancer tissues.

      What has it found? The E3N cohort has produced a spectrum of results regarding the complex
      roles played by nutrition, hormonal factors, physical activity, anthropometric
      characteristics and other major lifestyle-related factors with respect to various diseases.
observational model: Cohort
time perspective: Prospective
measure: Anthropometric measurements
time frame: From 1990 until now
description: Height, weight, hip circumference and waist circumference
measure: Educational level
time frame: 1990
measure: Professional activity
time frame: 1992 and 2005
description: Insee categories
measure: Age at cessation of activity
time frame: From 2005 until now
measure: Menstrual factors
time frame: From 1990 to 2002
description: Age at menarche, length of menstrual cycle
measure: Reproductive history
time frame: From 1990 to 1992
description: Number of pregnancies, age at each pregnancy, durations and outcomes of pregnancies, breastfeeding, infertility
measure: Menopause
time frame: 1990, 1995, 1997, 2000, 2002, 2005
description: Age, type
measure: Hormonal Treatments
time frame: From 1992 to 2008
description: Menopausal Hormonal Treatments (MHT), oral contraceptives
measure: Tobacco consumption
time frame: From 1990 until now
description: Type, quantity, time of smoking
measure: Alcohol consumption
time frame: 1993, 1997, 2005
description: Type of alcohol, quantity
measure: Physical activity
time frame: 1990,1997,2002, 2005, 2014
description: Moderate and intense activity, sedentarity
measure: Diet questionnaire
time frame: 1993 and 2002
description: Precise annual diet questionnaire
measure: Family history of diseases
time frame: 1990 to 2005
description: Cancer, diabetes and cardiovascular diseases
measure: Medication use
time frame: From 1990 until now
description: linked with the drug reimbursement files from the health insurance
measure: Medical and surgical history
time frame: From 1990 until now
measure: Mental Health
time frame: From 1990 until now
description: Centre for Epidemiologic Studies Depression Scale (CESD) and Depression
measure: Health outcomes
time frame: From 1990 until now
25000 blood samples; 47000 saliva samples
study pop: 
sampling method: Probability Sample
criteria: 
gender: Female
minimum age: 40 Years
maximum age: N/A
healthy volunteers: Accepts Healthy Volunteers
last name: Gianluca Severi, PhD
role: Study Director
affiliation: INSERM (Institut National de la Sante et de la Recherche Medicale)
last name: Marie-Christine Boutron-Ruault, PhD
role: Principal Investigator
affiliation: INSERM (Institut National de la Sante et de la Recherche Medicale)
url: http://www.e3n.fr
description: website of the study
citation: Clavel-Chapelon F; E3N Study Group. Cohort Profile: The French E3N Cohort Study. Int J Epidemiol. 2015 Jun;44(3):801-9. doi: 10.1093/ije/dyu184. Epub 2014 Sep 10.
PMID: 25212479
responsible party type: Sponsor
mesh term: Endometrial Neoplasms
mesh term: Crohn Disease
mesh term: Inflammatory Bowel Diseases
mesh term: Parkinson Disease
mesh term: Endometriosis
mesh term: Cardiovascular Diseases