<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/NCT04489069</url>
  </required_header>
  <id_info>
    <org_study_id>212/2019-VERSIONE2</org_study_id>
    <nct_id>NCT04489069</nct_id>
  </id_info>
  <brief_title>Developmental Psychopathology and the Gene-environment Interaction</brief_title>
  <acronym>TwinAger</acronym>
  <official_title>Multimodal and Multi-source Study of Developmental Psychopathology in Twin and Youth Cohorts: Integration of Neuroimaging, Neuropsychology and Gene-environment Measures</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>IRCCS Eugenio Medea</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>IRCCS Eugenio Medea</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>
      The present is a followup study that aims at investigating the effect of genetic and&#xD;
      environmental factors on the possible development of psychopathological conditions in a&#xD;
      longitudinal perspective.&#xD;
&#xD;
      The final goal is to understand those factors that causing vulnerability to mental illness,&#xD;
      eventually allowing better prevention and early detections of those persons with mental&#xD;
      illness.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The developmental psychopathology aims at studying the possible paths that psychiatric&#xD;
      conditions may take from childhood, through adolescence till early adulthood. This&#xD;
      developmental perspective has the final goal of allowing prevention and early detection of&#xD;
      mental illness, which in turn should translate into better prognosis and outcomes.&#xD;
&#xD;
      Longitudinal research allows a better grasp on the illness etiology as it gives the&#xD;
      opportunity of directly investigate the possible causal mechanisms and of defining the&#xD;
      origins of psychopathological condition in adults.&#xD;
&#xD;
      Many factors of risk interact, across neurodevelopment, in determining the person's&#xD;
      vulnerability to mental illness. For instance, temperament and psychopathological factors&#xD;
      were proved to have a role. However, the existing knowledge is still fragmented and should be&#xD;
      integrated by new knowledge on genetic and environmental factors. Thus, combining&#xD;
      observations of neurodevelopment, as measured with neuro-imaging techniques at subsequent&#xD;
      timepoints, with psychopathological and neuropsychological evaluations, as well as with&#xD;
      detailed information on genetic, environmental and temperamental indexes, is crucial, as no&#xD;
      similar exhaustive investigations are still available.&#xD;
&#xD;
      Furthermore, it must be bared in mind that the gene by environment interaction generates&#xD;
      complex epigenetic effects on neurodevelopment, which should be monitored through a longer&#xD;
      time lapse.&#xD;
&#xD;
      This topic has been studying this topic for years, by research groups with sites in Friuli&#xD;
      Venezia Giulia and Bosisio Parini (Lecco, Lombardia), by mean of cross-sectional and&#xD;
      longitudinal studies, involving samples of children and adolescents at risk of&#xD;
      psychopathology and referred because of behavioral and/or emotional difficulties, experienced&#xD;
      in the past or still ongoing. Also, the research involved a cohort of Twins recruited from&#xD;
      the normal population and whose data would allow more fine tuned analyses of the bene by&#xD;
      environment interaction.&#xD;
&#xD;
      In those first phases of study, instruments assessing the psychopathological risk were&#xD;
      adapted to the Italian population and the associated cognitive marker were identified.&#xD;
&#xD;
      Also, some analysis investigated the effect of the environment on the psychopathological&#xD;
      risk. Moreover, the influence of genetic factors is under now study, mainly focussing on&#xD;
      epigenetic factors.&#xD;
&#xD;
      The research that is presented here is the followup of the previous investigations. In the&#xD;
      previous year (2019) 33 participants underwent the follow up from the sample of children at&#xD;
      psychopathological risk and who were chidden/adolescents at the time of the baseline&#xD;
      evaluation.&#xD;
&#xD;
      During the current year the Twins cohort will be followed up. Half or more of the&#xD;
      participants tested ad the baseline are expected to participate, which correspond to about 30&#xD;
      couples (60 participants). The subjects will undergo i) a magnetic resonance, including&#xD;
      structural MRI, DTI, resting state fMRI, fMRI (during the fMRI sequences a concurrent task,&#xD;
      tapping attention and emotional processes, is presented); ii) a psychopathological&#xD;
      evaluation; iii) a self-rating evaluation, filling questionnaires measuring temperaments and&#xD;
      assessing the possible presence of behavioral problems; iv) a neurocognitive evaluation; v) a&#xD;
      drawing of biological-genetic sample (saliva).&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date type="Actual">January 16, 2019</start_date>
  <completion_date type="Anticipated">December 2021</completion_date>
  <primary_completion_date type="Anticipated">December 2021</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Other</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Magnetic Resonance (MRI) of the Brain - MRI signal allowing tridimensional multiplanar reconstruction of the brain's structures</measure>
    <time_frame>10 minutes</time_frame>
    <description>anatomical images obtained with high definition T1 weighted sequences of radio frequencies - the measure is a &quot;signal (in Hz) to noise ratio&quot; which is obtained from each voxel (tiny 3D portions of the brain)</description>
  </primary_outcome>
  <primary_outcome>
    <measure>MRI signal measuring the diffusion of weather particles across brain connections - Diffusion Tensor Imagning (DTI)</measure>
    <time_frame>10 minutes</time_frame>
    <description>measures of the brain microstructure and connectivity - as in all MRI techniques, the measure is a &quot;signal (in Hz) to noise ratio&quot; which is obtained from each voxel (tiny 3D portions of the brain)</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Functional Magnetic Resonance (fMRI) - MRI signal allowing to measure local brain's activity</measure>
    <time_frame>20 minutes</time_frame>
    <description>BOLD signal reflecting the brain activity that is concurrent to the execution of the Continuous Performance Test associated to emotional stimuli, as well as at rest - as in all MRI techniques, the measure is a &quot;signal (in Hz) to noise ratio&quot; which is obtained from each voxel (tiny 3D portions of the brain)</description>
  </primary_outcome>
  <primary_outcome>
    <measure>clinical evaluation by mean of structures interviews - different interviews have different scales. In most of the cases the presence/absence of a psychiatric symptom is evaluated</measure>
    <time_frame>2 hours</time_frame>
    <description>diagnosis or scores reflecting the degree of the presence or absence of a psychopathological condition or reflecting the personal temperament - The measures may vary on scales, for the most part the presence/absence (0-1) is recorded</description>
  </primary_outcome>
  <primary_outcome>
    <measure>neurocognitive evaluation - tests assessing general IQ, ability to produce words, drawing skills, attention's ability, memory.</measure>
    <time_frame>2 hours</time_frame>
    <description>the output vary according to the test - they are accuracy scores (number of correct answers) or reaction times (milliseconds)</description>
  </primary_outcome>
  <primary_outcome>
    <measure>sample of saliva</measure>
    <time_frame>&gt;10 minutes for drawing the sample</time_frame>
    <description>DNA single-nucleotide polymorphism from</description>
  </primary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">60</enrollment>
  <condition>Developmental Psychological Disorder</condition>
  <arm_group>
    <arm_group_label>Clinical, neuropsychological and MRI evaluations</arm_group_label>
    <arm_group_type>Other</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Diagnostic Test</intervention_type>
    <intervention_name>MRI</intervention_name>
    <description>Magnetic Resonance Imaging (sturctural MRI, fMRI resting state and task related, DTI)</description>
    <arm_group_label>Clinical, neuropsychological and MRI evaluations</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Diagnostic Test</intervention_type>
    <intervention_name>Clinical and Neuropsychological evaluations</intervention_name>
    <description>Clinical interviews and neuropsychological tests (paper/pencil and computer based)</description>
    <arm_group_label>Clinical, neuropsychological and MRI evaluations</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Diagnostic Test</intervention_type>
    <intervention_name>Drawing DNA sample</intervention_name>
    <description>Saliva sample</description>
    <arm_group_label>Clinical, neuropsychological and MRI evaluations</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  participants who already took part to the previous baseline evaluations carried out in&#xD;
             our centers and signed consent to be contacted for future follow up&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Current or previous neurological illness or trauma that involved the brain.&#xD;
&#xD;
          -  Sensory impairments that can hamper the correct execution of the neurocognitive tasks&#xD;
             and interviews.&#xD;
&#xD;
          -  Intellectual disability (i.e. IQ&lt;70 as estimated with the Wechsler Adult Intelligence&#xD;
             Scale or the Wechsler Intelligence Scale for Children)&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>15 Years</minimum_age>
    <maximum_age>35 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Carolina Bonivento, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>IRCCS E.Medea</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Carolina Bonivento, PhD</last_name>
    <phone>‭+39 0432 559148</phone>
    <email>carolina.bonivento@lanostrafamiglia.it</email>
  </overall_contact>
  <location>
    <facility>
      <name>IRCCS E.Medea</name>
      <address>
        <city>San Vito Al Tagliamento</city>
        <state>Pordenone</state>
        <zip>33078</zip>
        <country>Italy</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Carolina Bonivento, PhD</last_name>
      <phone>+39 0432 559148‬</phone>
      <email>carolina.bonivento@lanostrafamiglia.it</email>
    </contact>
  </location>
  <location_countries>
    <country>Italy</country>
  </location_countries>
  <verification_date>July 2020</verification_date>
  <study_first_submitted>March 30, 2020</study_first_submitted>
  <study_first_submitted_qc>July 24, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 28, 2020</study_first_posted>
  <last_update_submitted>July 24, 2020</last_update_submitted>
  <last_update_submitted_qc>July 24, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">July 28, 2020</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>Mental Disorders</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </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/NCT04489069
org study id: 212/2019-VERSIONE2
nct id: NCT04489069
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
The present is a followup study that aims at investigating the effect of genetic and
      environmental factors on the possible development of psychopathological conditions in a
      longitudinal perspective.

      The final goal is to understand those factors that causing vulnerability to mental illness,
      eventually allowing better prevention and early detections of those persons with mental
      illness.
The developmental psychopathology aims at studying the possible paths that psychiatric
      conditions may take from childhood, through adolescence till early adulthood. This
      developmental perspective has the final goal of allowing prevention and early detection of
      mental illness, which in turn should translate into better prognosis and outcomes.

      Longitudinal research allows a better grasp on the illness etiology as it gives the
      opportunity of directly investigate the possible causal mechanisms and of defining the
      origins of psychopathological condition in adults.

      Many factors of risk interact, across neurodevelopment, in determining the person's
      vulnerability to mental illness. For instance, temperament and psychopathological factors
      were proved to have a role. However, the existing knowledge is still fragmented and should be
      integrated by new knowledge on genetic and environmental factors. Thus, combining
      observations of neurodevelopment, as measured with neuro-imaging techniques at subsequent
      timepoints, with psychopathological and neuropsychological evaluations, as well as with
      detailed information on genetic, environmental and temperamental indexes, is crucial, as no
      similar exhaustive investigations are still available.

      Furthermore, it must be bared in mind that the gene by environment interaction generates
      complex epigenetic effects on neurodevelopment, which should be monitored through a longer
      time lapse.

      This topic has been studying this topic for years, by research groups with sites in Friuli
      Venezia Giulia and Bosisio Parini (Lecco, Lombardia), by mean of cross-sectional and
      longitudinal studies, involving samples of children and adolescents at risk of
      psychopathology and referred because of behavioral and/or emotional difficulties, experienced
      in the past or still ongoing. Also, the research involved a cohort of Twins recruited from
      the normal population and whose data would allow more fine tuned analyses of the bene by
      environment interaction.

      In those first phases of study, instruments assessing the psychopathological risk were
      adapted to the Italian population and the associated cognitive marker were identified.

      Also, some analysis investigated the effect of the environment on the psychopathological
      risk. Moreover, the influence of genetic factors is under now study, mainly focussing on
      epigenetic factors.

      The research that is presented here is the followup of the previous investigations. In the
      previous year (2019) 33 participants underwent the follow up from the sample of children at
      psychopathological risk and who were chidden/adolescents at the time of the baseline
      evaluation.

      During the current year the Twins cohort will be followed up. Half or more of the
      participants tested ad the baseline are expected to participate, which correspond to about 30
      couples (60 participants). The subjects will undergo i) a magnetic resonance, including
      structural MRI, DTI, resting state fMRI, fMRI (during the fMRI sequences a concurrent task,
      tapping attention and emotional processes, is presented); ii) a psychopathological
      evaluation; iii) a self-rating evaluation, filling questionnaires measuring temperaments and
      assessing the possible presence of behavioral problems; iv) a neurocognitive evaluation; v) a
      drawing of biological-genetic sample (saliva).
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Other
masking: None (Open Label)
measure: Magnetic Resonance (MRI) of the Brain - MRI signal allowing tridimensional multiplanar reconstruction of the brain's structures
time frame: 10 minutes
description: anatomical images obtained with high definition T1 weighted sequences of radio frequencies - the measure is a "signal (in Hz) to noise ratio" which is obtained from each voxel (tiny 3D portions of the brain)
measure: MRI signal measuring the diffusion of weather particles across brain connections - Diffusion Tensor Imagning (DTI)
time frame: 10 minutes
description: measures of the brain microstructure and connectivity - as in all MRI techniques, the measure is a "signal (in Hz) to noise ratio" which is obtained from each voxel (tiny 3D portions of the brain)
measure: Functional Magnetic Resonance (fMRI) - MRI signal allowing to measure local brain's activity
time frame: 20 minutes
description: BOLD signal reflecting the brain activity that is concurrent to the execution of the Continuous Performance Test associated to emotional stimuli, as well as at rest - as in all MRI techniques, the measure is a "signal (in Hz) to noise ratio" which is obtained from each voxel (tiny 3D portions of the brain)
measure: clinical evaluation by mean of structures interviews - different interviews have different scales. In most of the cases the presence/absence of a psychiatric symptom is evaluated
time frame: 2 hours
description: diagnosis or scores reflecting the degree of the presence or absence of a psychopathological condition or reflecting the personal temperament - The measures may vary on scales, for the most part the presence/absence (0-1) is recorded
measure: neurocognitive evaluation - tests assessing general IQ, ability to produce words, drawing skills, attention's ability, memory.
time frame: 2 hours
description: the output vary according to the test - they are accuracy scores (number of correct answers) or reaction times (milliseconds)
measure: sample of saliva
time frame: >10 minutes for drawing the sample
description: DNA single-nucleotide polymorphism from
arm group label: Clinical, neuropsychological and MRI evaluations
arm group type: Other
intervention type: Diagnostic Test
intervention name: MRI
description: Magnetic Resonance Imaging (sturctural MRI, fMRI resting state and task related, DTI)
arm group label: Clinical, neuropsychological and MRI evaluations
intervention type: Diagnostic Test
intervention name: Clinical and Neuropsychological evaluations
description: Clinical interviews and neuropsychological tests (paper/pencil and computer based)
arm group label: Clinical, neuropsychological and MRI evaluations
intervention type: Diagnostic Test
intervention name: Drawing DNA sample
description: Saliva sample
arm group label: Clinical, neuropsychological and MRI evaluations
criteria: 
gender: All
minimum age: 15 Years
maximum age: 35 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Carolina Bonivento, PhD
role: Principal Investigator
affiliation: IRCCS E.Medea
last name: Carolina Bonivento, PhD
phone: ‭+39 0432 559148
email: carolina.bonivento@lanostrafamiglia.it
facility: 
status: Recruiting
contact: 
country: Italy
responsible party type: Sponsor
mesh term: Mental Disorders
sharing ipd: No