<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/NCT03834402</url>
  </required_header>
  <id_info>
    <org_study_id>2251</org_study_id>
    <nct_id>NCT03834402</nct_id>
  </id_info>
  <brief_title>INTERCEPTOR Project: From MCI to Dementia</brief_title>
  <acronym>INTERCEPTOR</acronym>
  <official_title>Interceptor Project: On Early Diagnosis Of The Prodromal Stage Of Alzheimer Disease. The Progression From Mild Cognitive Impairment (Mci) To Dementia: The Role Of Biomarkers In Early Interception Of Patients Candidate For Prescription Of Future Disease-Modifying Drugs</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Catholic University of the Sacred Heart</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Ministry of Health, Italy</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Agenzia Italiana del Farmaco</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Catholic University of the Sacred Heart</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>
      In the next years a number of phase 2-3 trials which utilize experimental drugs possibly&#xD;
      disease modifying for Alzheimer Dementia will reach their conclusion. This dense clinical&#xD;
      trials activity has triggered a fundamental question both from Patients and Scientific&#xD;
      Communities and Health Authorities/Insurances: on which basis will the new drugs -if&#xD;
      effective-be distributed to patients or at-risk population? This question mainly deals with&#xD;
      the &quot;MCI prodromal to AD&quot;condition since the MCI population actually includes about 50% of&#xD;
      those who will progress to AD (the real &quot;prodromic to AD&quot; MCI form) while the remaining 50%&#xD;
      will never convert to AD.&#xD;
&#xD;
      The INTERCEPTOR project is focused on the prodromic AD condition (IWG2) or the MCI condition&#xD;
      (NIA-AA) which form the neuropsychological point of view and is characterized by means of:&#xD;
      cognitive questionnaires, screening test (MMSE), extended neuropsychological evaluation.&#xD;
&#xD;
      The study is an observational, longitudinal cohort one, in which the baseline clinical and&#xD;
      biomarkers characteristics of the enrolled MCI subjects at baseline will be compared for&#xD;
      those classified as &quot;AD converters&quot; after 3.0 years of follow-up with respect to those&#xD;
      &quot;non-converters&quot;. MCI subjects who will convert to other forms of dementia will be examined&#xD;
      separately. It will be considered the conversion to Alzheimer's disease within 3.0 years&#xD;
      after diagnosis of MCI, together with the assessment of those who remain in a stable&#xD;
      condition and those who have a reversion to normal cognitive profile. People with MCI who&#xD;
      convert to other forms of dementia will be considered separately. The biomarker or a set of&#xD;
      biomarkers that can predict the conversion to Alzheimer's disease with higher accuracy will&#xD;
      be evaluated.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      In the next 8 years a number of phase 2-3 trials will end up which utilize experimental drugs&#xD;
      possibly disease modifying for Alzheimer Dementia. They target different disease stages:&#xD;
      mild-moderate AD, 'early' AD, MCI prodromic to AD (MCI + for biomarkers heralding progression&#xD;
      to AD), pre-symptomatic AD in pathogenetic gene mutation carriers of familiar AD forms. This&#xD;
      dense clinical trials activity has triggered a fundamental question both from Patients and&#xD;
      Scientific Communities and Health Authorities/Insurances: on which basis will the new drugs&#xD;
      -if effective-be distributed to patients or at-risk population? This question mainly deals&#xD;
      with the &quot;MCI prodromal to AD&quot;condition since the MCI population actually includes about 50%&#xD;
      of those who will progress to AD (the real &quot;prodromic to AD&quot; MCI form) while the remaining&#xD;
      50% will never convert to AD. Since the new drugs -if effective- will carry both elevated&#xD;
      unit costs and not marginal side-effects, they should be administered selectively to those&#xD;
      MCI with a severely high risk of conversion (i.e. 90% or more) and particularly to those with&#xD;
      a highrisk of rapid conversion (1-2 years from diagnosis of the MCI condition).&#xD;
&#xD;
      The INTERCEPTOR project is focused on the prodromic AD condition (IWG2) or the MCI condition&#xD;
      (NIA-AA) which form the neuropsychological point of view and is characterized by means of:&#xD;
      cognitive questionnaire, screening test (MMSE), extended neuropsychological evaluation (incl.&#xD;
      2 episodic memory tests, language test, visuo-spatial abilities evaluation, behavioural&#xD;
      scales, functional scales (Annex), full neurological examination. CDR must be 0.5. Atypical&#xD;
      types of clinical presentations must be particularly considered (i.e. non amnesic debut) for&#xD;
      a differential diagnosis where the role of biomarkers is pivotal.&#xD;
&#xD;
      In Italy, according to a recent study, an MCI prevalence of 5.9% has been evaluated in over&#xD;
      60 yrs population, with an increase of 4.5% between 60 &amp; 69 yrs, of 5.8% between 70 &amp; 79 yrs,&#xD;
      and up to 7.1% in the 80 - 89 yrs range. On this epidemiological basis about 735.000 MCI&#xD;
      cases are estimated for 2016in the resident Italian population. Multicentric non therapeutic&#xD;
      cohort study in subjects fulfilling the MCI &quot;core&quot; criteria as defined by the National&#xD;
      Institute on Aging-Alzheimer's Association workgroups on diagnostic guidelines for&#xD;
      Alzheimer's disease. The study design reflect a longitudinal cohort study in which the&#xD;
      baseline clinical and biomarkers characteristics of the enrolled MCI subjects at baseline&#xD;
      will be compared for those classified as &quot;AD converters&quot; after 3.0 years of follow-up with&#xD;
      respect to those &quot;non-converters&quot;. MCI subjects who will convert to other forms of dementia&#xD;
      will be examined separately.&#xD;
&#xD;
      All the medications at baseline are allowed without modifications for the whole protocol&#xD;
      except for urgencies.&#xD;
&#xD;
      Neuropsychological follow-up tests will be carried out at 6 months intervals (total 7 from&#xD;
      T0= baseline to T6= 42 months).&#xD;
&#xD;
      Within 60 days from T0 biomarkers must be carried out/collected including:&#xD;
&#xD;
      MMSE &amp; DRF - FCSRT) DNA extraction and ApoE typing Lumbar Puncture for Beta/Tau metabolites&#xD;
      EEG for brain connectivity with graph theory MRI + hippocampal volumetry (18F)FDG-PET&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">May 1, 2019</start_date>
  <completion_date type="Anticipated">December 31, 2023</completion_date>
  <primary_completion_date type="Actual">October 1, 2019</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>MCI converting to AD</measure>
    <time_frame>3 years</time_frame>
    <description>Percentage of enrolled patients that convert from MCI to Alzheimer's disease within 3.0 years.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>PREDICTING BIOMARKERS</measure>
    <time_frame>4.5 years</time_frame>
    <description>Identify the biomarker or the set of biomarker that predict, using statistical techniques, in the most precise way the &quot;conversion from MCI to AD&quot; event.</description>
  </secondary_outcome>
  <enrollment type="Anticipated">500</enrollment>
  <condition>Mild Cognitive Impairment</condition>
  <condition>Alzheimer Disease</condition>
  <biospec_retention>Samples With DNA</biospec_retention>
  <biospec_descr>
    <textblock>
      ApoE test&#xD;
    </textblock>
  </biospec_descr>
  <eligibility>
    <study_pop>
      <textblock>
        MCI subjects&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. age between 50 and 85 years;&#xD;
&#xD;
          2. age and education corrected Mini Mental State Examination score equal or superior to&#xD;
             24/30;&#xD;
&#xD;
          3. Clinical Dementia Rating (CDR) global score of 0.5;&#xD;
&#xD;
          4. concerns about cognitive modifications, expressed as subjective complaints by the&#xD;
             subject, or by impression by a close acquaintance or an expert clinician;&#xD;
&#xD;
          5. defective performance with reference to age and education matched controls in one&#xD;
             cognitive domain (memory, executive function, attention, language, visuospatial&#xD;
             function): if repeated assessments are available, evidence of performance decline;&#xD;
&#xD;
          6. preserved functional autonomy: the subject remains fully independent, even if specific&#xD;
             performances may be slower, less efficient than usual level, with occasional errors;&#xD;
&#xD;
          7. no dementia: the cognitive modifications do not significantly hamper social function&#xD;
             or work activities.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. history of cerebrovascular disease (i.e. stroke episodes), alcohol abuse, severe&#xD;
             medical disorders associated with cognitive impairment (organ failures, endocrine&#xD;
             disorders, in particular thyroid disease and B12/folates deficiency); neuroimaging&#xD;
             evidence of other potential causes of cognitive decline (e.g. subdural haematoma,&#xD;
             malignancy etc.); chronic treatment with psychotropic drugs; women in reproductive&#xD;
             age;&#xD;
&#xD;
          2. history of malignancy &lt; 5 years;&#xD;
&#xD;
          3. contraindications for Magnetic Resonance Imaging (MRI): pacemaker; spinal stimulators;&#xD;
             defibrillator; any other condition incompatible with MRI acquisition;&#xD;
&#xD;
          4. presence of spinal malformations or any other contraindications to lumbar puncture,&#xD;
             according to the investigator's judgement;&#xD;
&#xD;
          5. HIV infection;&#xD;
&#xD;
          6. use of drugs potentially affecting cognitive function, according to the investigator's&#xD;
             judgement;&#xD;
&#xD;
          7. subjects are not allowed to participate in any trial with experimental drug;&#xD;
&#xD;
        Exclusion criteria specific to lumbar puncture:&#xD;
&#xD;
        Patients who refuse to or cannot temporarily interrupt antiplatelet or anticoagulant&#xD;
        therapy 14 days prior to sampling visit.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>50 Years</minimum_age>
    <maximum_age>85 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Paolo Maria Rossini, Prof</last_name>
    <role>Principal Investigator</role>
    <affiliation>Catholic University of Sacred Heart</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Policlinico Agostino Gemelli</name>
      <address>
        <city>Rome</city>
        <zip>00168</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Italy</country>
  </location_countries>
  <reference>
    <citation>Albert MS, DeKosky ST, Dickson D, Dubois B, Feldman HH, Fox NC, Gamst A, Holtzman DM, Jagust WJ, Petersen RC, Snyder PJ, Carrillo MC, Thies B, Phelps CH. The diagnosis of mild cognitive impairment due to Alzheimer's disease: recommendations from the National Institute on Aging-Alzheimer's Association workgroups on diagnostic guidelines for Alzheimer's disease. Alzheimers Dement. 2011 May;7(3):270-9. doi: 10.1016/j.jalz.2011.03.008. Epub 2011 Apr 21.</citation>
    <PMID>21514249</PMID>
  </reference>
  <reference>
    <citation>Appollonio I, Leone M, Isella V, Piamarta F, Consoli T, Villa ML, Forapani E, Russo A, Nichelli P. The Frontal Assessment Battery (FAB): normative values in an Italian population sample. Neurol Sci. 2005 Jun;26(2):108-16. doi: 10.1007/s10072-005-0443-4.</citation>
    <PMID>15995827</PMID>
  </reference>
  <reference>
    <citation>Arevalo-Rodriguez I, Smailagic N, Roque I Figuls M, Ciapponi A, Sanchez-Perez E, Giannakou A, Pedraza OL, Bonfill Cosp X, Cullum S. Mini-Mental State Examination (MMSE) for the detection of Alzheimer's disease and other dementias in people with mild cognitive impairment (MCI). Cochrane Database Syst Rev. 2015 Mar 5;2015(3):CD010783. doi: 10.1002/14651858.CD010783.pub2.</citation>
    <PMID>25740785</PMID>
  </reference>
  <verification_date>August 2021</verification_date>
  <study_first_submitted>January 10, 2019</study_first_submitted>
  <study_first_submitted_qc>February 5, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">February 8, 2019</study_first_posted>
  <last_update_submitted>August 2, 2021</last_update_submitted>
  <last_update_submitted_qc>August 2, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">August 3, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Catholic University of the Sacred Heart</investigator_affiliation>
    <investigator_full_name>Paolo Maria Rossini</investigator_full_name>
    <investigator_title>Professor</investigator_title>
  </responsible_party>
  <keyword>Mild Cognitive Impairment</keyword>
  <keyword>Alzheimer Disease</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Alzheimer Disease</mesh_term>
    <mesh_term>Dementia</mesh_term>
    <mesh_term>Cognitive Dysfunction</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
    <ipd_description>IPD will only be at the disposal of the recruiting centers involved in the study</ipd_description>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03834402
org study id: 2251
nct id: NCT03834402
lead sponsor: 
collaborator: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
In the next years a number of phase 2-3 trials which utilize experimental drugs possibly
      disease modifying for Alzheimer Dementia will reach their conclusion. This dense clinical
      trials activity has triggered a fundamental question both from Patients and Scientific
      Communities and Health Authorities/Insurances: on which basis will the new drugs -if
      effective-be distributed to patients or at-risk population? This question mainly deals with
      the "MCI prodromal to AD"condition since the MCI population actually includes about 50% of
      those who will progress to AD (the real "prodromic to AD" MCI form) while the remaining 50%
      will never convert to AD.

      The INTERCEPTOR project is focused on the prodromic AD condition (IWG2) or the MCI condition
      (NIA-AA) which form the neuropsychological point of view and is characterized by means of:
      cognitive questionnaires, screening test (MMSE), extended neuropsychological evaluation.

      The study is an observational, longitudinal cohort one, in which the baseline clinical and
      biomarkers characteristics of the enrolled MCI subjects at baseline will be compared for
      those classified as "AD converters" after 3.0 years of follow-up with respect to those
      "non-converters". MCI subjects who will convert to other forms of dementia will be examined
      separately. It will be considered the conversion to Alzheimer's disease within 3.0 years
      after diagnosis of MCI, together with the assessment of those who remain in a stable
      condition and those who have a reversion to normal cognitive profile. People with MCI who
      convert to other forms of dementia will be considered separately. The biomarker or a set of
      biomarkers that can predict the conversion to Alzheimer's disease with higher accuracy will
      be evaluated.
In the next 8 years a number of phase 2-3 trials will end up which utilize experimental drugs
      possibly disease modifying for Alzheimer Dementia. They target different disease stages:
      mild-moderate AD, 'early' AD, MCI prodromic to AD (MCI + for biomarkers heralding progression
      to AD), pre-symptomatic AD in pathogenetic gene mutation carriers of familiar AD forms. This
      dense clinical trials activity has triggered a fundamental question both from Patients and
      Scientific Communities and Health Authorities/Insurances: on which basis will the new drugs
      -if effective-be distributed to patients or at-risk population? This question mainly deals
      with the "MCI prodromal to AD"condition since the MCI population actually includes about 50%
      of those who will progress to AD (the real "prodromic to AD" MCI form) while the remaining
      50% will never convert to AD. Since the new drugs -if effective- will carry both elevated
      unit costs and not marginal side-effects, they should be administered selectively to those
      MCI with a severely high risk of conversion (i.e. 90% or more) and particularly to those with
      a highrisk of rapid conversion (1-2 years from diagnosis of the MCI condition).

      The INTERCEPTOR project is focused on the prodromic AD condition (IWG2) or the MCI condition
      (NIA-AA) which form the neuropsychological point of view and is characterized by means of:
      cognitive questionnaire, screening test (MMSE), extended neuropsychological evaluation (incl.
      2 episodic memory tests, language test, visuo-spatial abilities evaluation, behavioural
      scales, functional scales (Annex), full neurological examination. CDR must be 0.5. Atypical
      types of clinical presentations must be particularly considered (i.e. non amnesic debut) for
      a differential diagnosis where the role of biomarkers is pivotal.

      In Italy, according to a recent study, an MCI prevalence of 5.9% has been evaluated in over
      60 yrs population, with an increase of 4.5% between 60 & 69 yrs, of 5.8% between 70 & 79 yrs,
      and up to 7.1% in the 80 - 89 yrs range. On this epidemiological basis about 735.000 MCI
      cases are estimated for 2016in the resident Italian population. Multicentric non therapeutic
      cohort study in subjects fulfilling the MCI "core" criteria as defined by the National
      Institute on Aging-Alzheimer's Association workgroups on diagnostic guidelines for
      Alzheimer's disease. The study design reflect a longitudinal cohort study in which the
      baseline clinical and biomarkers characteristics of the enrolled MCI subjects at baseline
      will be compared for those classified as "AD converters" after 3.0 years of follow-up with
      respect to those "non-converters". MCI subjects who will convert to other forms of dementia
      will be examined separately.

      All the medications at baseline are allowed without modifications for the whole protocol
      except for urgencies.

      Neuropsychological follow-up tests will be carried out at 6 months intervals (total 7 from
      T0= baseline to T6= 42 months).

      Within 60 days from T0 biomarkers must be carried out/collected including:

      MMSE & DRF - FCSRT) DNA extraction and ApoE typing Lumbar Puncture for Beta/Tau metabolites
      EEG for brain connectivity with graph theory MRI + hippocampal volumetry (18F)FDG-PET
observational model: Cohort
time perspective: Prospective
measure: MCI converting to AD
time frame: 3 years
description: Percentage of enrolled patients that convert from MCI to Alzheimer's disease within 3.0 years.
measure: PREDICTING BIOMARKERS
time frame: 4.5 years
description: Identify the biomarker or the set of biomarker that predict, using statistical techniques, in the most precise way the "conversion from MCI to AD" event.
ApoE test
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 50 Years
maximum age: 85 Years
healthy volunteers: No
last name: Paolo Maria Rossini, Prof
role: Principal Investigator
affiliation: Catholic University of Sacred Heart
facility: 
country: Italy
citation: Albert MS, DeKosky ST, Dickson D, Dubois B, Feldman HH, Fox NC, Gamst A, Holtzman DM, Jagust WJ, Petersen RC, Snyder PJ, Carrillo MC, Thies B, Phelps CH. The diagnosis of mild cognitive impairment due to Alzheimer's disease: recommendations from the National Institute on Aging-Alzheimer's Association workgroups on diagnostic guidelines for Alzheimer's disease. Alzheimers Dement. 2011 May;7(3):270-9. doi: 10.1016/j.jalz.2011.03.008. Epub 2011 Apr 21.
PMID: 21514249
citation: Appollonio I, Leone M, Isella V, Piamarta F, Consoli T, Villa ML, Forapani E, Russo A, Nichelli P. The Frontal Assessment Battery (FAB): normative values in an Italian population sample. Neurol Sci. 2005 Jun;26(2):108-16. doi: 10.1007/s10072-005-0443-4.
PMID: 15995827
citation: Arevalo-Rodriguez I, Smailagic N, Roque I Figuls M, Ciapponi A, Sanchez-Perez E, Giannakou A, Pedraza OL, Bonfill Cosp X, Cullum S. Mini-Mental State Examination (MMSE) for the detection of Alzheimer's disease and other dementias in people with mild cognitive impairment (MCI). Cochrane Database Syst Rev. 2015 Mar 5;2015(3):CD010783. doi: 10.1002/14651858.CD010783.pub2.
PMID: 25740785
responsible party type: Principal Investigator
investigator affiliation: Catholic University of the Sacred Heart
investigator full name: Paolo Maria Rossini
investigator title: Professor
mesh term: Alzheimer Disease
mesh term: Dementia
mesh term: Cognitive Dysfunction
sharing ipd: No
ipd description: IPD will only be at the disposal of the recruiting centers involved in the study