<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/NCT04437290</url>
  </required_header>
  <id_info>
    <org_study_id>STUDY00009617</org_study_id>
    <secondary_id>P30AG066509</secondary_id>
    <nct_id>NCT04437290</nct_id>
  </id_info>
  <brief_title>University of Washington Alzheimer's Disease Research Center (UW ADRC) Imaging &amp; Biomarker Core</brief_title>
  <official_title>University of Washington Alzheimer's Disease Research Center (UW ADRC) Imaging &amp; Biomarker Core</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Washington</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>National Institute on Aging (NIA)</agency>
      <agency_class>NIH</agency_class>
    </collaborator>
    <collaborator>
      <agency>Ellison Foundation</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>University of Washington</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      This is a cross-sectional, observational study that characterizes research participants with&#xD;
      Alzheimer's disease (AD) for their patterns of brain degeneration with the investigational&#xD;
      tau positron emission tomography (PET) radiotracer [18F] MK-6240. The goal is to describe the&#xD;
      topographic pattern of involvement of cerebral brain regions (topographic phenotyping) in&#xD;
      early stage AD participants using tau PET in a sub-cohort of the University of Washington&#xD;
      Alzheimer's Disease Research Center (ADRC) Clinical Cohort, and to make this phenotype&#xD;
      information available to affiliated research studies at the University of Washington and to&#xD;
      the general scientific community via the National Alzheimer's Coordinating Center.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Memory loss and dementia, including Alzheimer's disease (AD), are heterogeneous in terms of&#xD;
      pattern of symptoms and brain atrophy, likely due to underlying variability in AD biological&#xD;
      processes, as well as comorbidity (separate diseases that co-occur with AD). The&#xD;
      correspondence between clinical findings and underlying cause is imperfect, though, and the&#xD;
      field has benefitted tremendously from development of biomarkers that can be used for&#xD;
      diagnosis, for estimation of the biological burden of pathology, and/or for tracking disease&#xD;
      trajectories. For example, in the National Institute on Aging-Alzheimer's Association&#xD;
      (NIA-AA) research framework, biomarkers of Amyloid beta, phosphorylated Tau, and&#xD;
      Neurodegeneration (A/T/N) standardize the separation of cases with Alzheimer pathophysiology&#xD;
      from those without it.&#xD;
&#xD;
      A sub-cohort of UW ADRC Clinical Core participants who have amyloid deposition (A+ by&#xD;
      cerebrospinal fluid [CSF] or amyloid PET) and mild degrees of cognitive impairment will be&#xD;
      investigated for their specific pattern of tau deposition with tau PET. Additionally,&#xD;
      participants who are thought to be resilient to Alzheimer disease, e.g. 85 years or older and&#xD;
      normal cognition, or A+ by CSF or amyloid PET and normal cognition, will also be investigated&#xD;
      for their specific pattern of tau deposition with tau PET.&#xD;
&#xD;
      The ADRC Imaging and Biomarker Core will conduct and analyze these scans, and store the data&#xD;
      in the Integrated Brain Imaging Center at the University of Washington Medical Center campus,&#xD;
      which is directed by the PI, Dr. Grabowski. It will also use other data collected by ADRC&#xD;
      Cores (such as neuropsychology testing) to perform other analysis, such as estimating&#xD;
      resilience measures (i.e. the ability of the brain to function well in spite of the presence&#xD;
      of AD).&#xD;
&#xD;
      This sub-cohort will aid in the investigation of Alzheimer's disease and related dementias&#xD;
      (ADRD) by providing a means to better understand the relationships between the spatial&#xD;
      patterns of tau deposition, neurodegeneration in the brain, cognitive symptoms, and&#xD;
      resilience. It will provide a ready source of potential participants to the larger research&#xD;
      community. By standardizing and supporting the collection imaging and CSF for research&#xD;
      participants with Alzheimer's disease and related dementias under the ADRC, we promote&#xD;
      research synergism and productivity across UW studies of AD and related disorders.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Not yet recruiting</overall_status>
  <start_date type="Anticipated">November 2022</start_date>
  <completion_date type="Anticipated">April 30, 2025</completion_date>
  <primary_completion_date type="Anticipated">April 30, 2025</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>tau PET SUVR image</measure>
    <time_frame>Day 1</time_frame>
    <description>Parametric [18F]MK6240 standardized uptake ratio images (SUVR) generated using an inferior cerebellar gray matter reference region.</description>
  </primary_outcome>
  <number_of_groups>1</number_of_groups>
  <enrollment type="Anticipated">300</enrollment>
  <condition>Alzheimer Disease</condition>
  <arm_group>
    <arm_group_label>Alzheimer disease</arm_group_label>
    <description>The group is composed of individuals with a consensus diagnosis of amnestic mild cognitive impairment (MCI) or amnestic multimodal MCI or dementia primarily attributed to Alzheimer's disease (AD), as determined by the UW ADRC Clinical Core. They will have age of presentation &gt; 55 years, sporadic onset, CDR (Clinical Dementia Rating Scale) score 0.5-1.0, and sufficient English competency to complete a standardized cognitive testing battery. All will have no contraindication to MRI and will have had an MRI scan in the UW ADRC Imaging and Biomarker Core. These participants will undergo PET scanning with the investigational tau tracer [18F] MK6240</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>investigational radiotracer [18F]MK6240</intervention_name>
    <description>Brain PET scan</description>
    <arm_group_label>Alzheimer disease</arm_group_label>
  </intervention>
  <eligibility>
    <study_pop>
      <textblock>
        Individuals with preclinical, prodromal, or mild dementia due to Alzheimer's disease, based&#xD;
        on amyloid biomarker evidence&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Amnestic MCI or Amnestic multimodal MCI or dementia primarily attributed to AD, by&#xD;
             consensus diagnosis in the ADRC Clinical Core;&#xD;
&#xD;
          2. Evidence of A+ T+ Alzheimer disease by CSF evaluation (e.g. low amyloid beta(AB)42 or&#xD;
             42/40 ratio and elevated p-181-tau); or evidence of A+ Alzheimer disease by amyloid&#xD;
             PET.&#xD;
&#xD;
          3. Age of presentation for first evaluation &gt; 55 years;&#xD;
&#xD;
          4. Sporadic onset, defined by not from a known autosomal dominant AD family and not more&#xD;
             than 1 first degree relative with dementia onset before age 65;&#xD;
&#xD;
          5. Clinical Dementia Rating scale (CDR) score 0.5 or 1.0;&#xD;
&#xD;
          6. English competency sufficient to complete cognitive testing battery to the&#xD;
             satisfaction of ADRC neuropsychologist;&#xD;
&#xD;
          7. MRI scan in the Clinical Core, with additional selection for topographic diversity,&#xD;
             based on the MRI imaging.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. History of symptomatic cerebrovascular disease (CVD) or CVD evaluated to contribute&#xD;
             significantly to cognitive impairments;&#xD;
&#xD;
          2. Parkinsonism, or meeting revised McKeith criteria for possible or probable Dementia&#xD;
             with Lewy bodies;&#xD;
&#xD;
          3. Contraindication to MRI scanning (e.g. metal implants, severe claustrophobia);&#xD;
&#xD;
          4. Premorbid history of neurologic disease that may contribute to cognitive impairment&#xD;
             (e.g. multiple sclerosis, epilepsy, brain tumor);&#xD;
&#xD;
          5. History of developmental dyslexia or other developmental disorder affecting validity&#xD;
             of cognitive tests. These exclusion criteria minimize comorbidity;&#xD;
&#xD;
          6. Pregnancy or breast-feeding.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>55 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Thomas J Grabowski, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Washington</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Christina Caso</last_name>
    <phone>206-221-9038</phone>
    <email>cdcaso@uw.edu</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Annika Noreen, PhD</last_name>
    <phone>206-685-1221</phone>
    <email>annikn@uw.edu</email>
  </overall_contact_backup>
  <reference>
    <citation>Lohith TG, Bennacef I, Vandenberghe R, Vandenbulcke M, Salinas CA, Declercq R, Reynders T, Telan-Choing NF, Riffel K, Celen S, Serdons K, Bormans G, Tsai K, Walji A, Hostetler ED, Evelhoch JL, Van Laere K, Forman M, Stoch A, Sur C, Struyk A. Brain Imaging of Alzheimer Dementia Patients and Elderly Controls with 18F-MK-6240, a PET Tracer Targeting Neurofibrillary Tangles. J Nucl Med. 2019 Jan;60(1):107-114. doi: 10.2967/jnumed.118.208215. Epub 2018 Jun 7.</citation>
    <PMID>29880509</PMID>
  </reference>
  <reference>
    <citation>Pascoal TA, Shin M, Kang MS, Chamoun M, Chartrand D, Mathotaarachchi S, Bennacef I, Therriault J, Ng KP, Hopewell R, Bouhachi R, Hsiao HH, Benedet AL, Soucy JP, Massarweh G, Gauthier S, Rosa-Neto P. In vivo quantification of neurofibrillary tangles with [18F]MK-6240. Alzheimers Res Ther. 2018 Jul 31;10(1):74. doi: 10.1186/s13195-018-0402-y.</citation>
    <PMID>30064520</PMID>
  </reference>
  <reference>
    <citation>Koole M, Lohith TG, Valentine JL, Bennacef I, Declercq R, Reynders T, Riffel K, Celen S, Serdons K, Bormans G, Ferry-Martin S, Laroque P, Walji A, Hostetler ED, Briscoe RJ, de Hoon J, Sur C, Van Laere K, Struyk A. Preclinical Safety Evaluation and Human Dosimetry of [18F]MK-6240, a Novel PET Tracer for Imaging Neurofibrillary Tangles. Mol Imaging Biol. 2020 Feb;22(1):173-180. doi: 10.1007/s11307-019-01367-w.</citation>
    <PMID>31111397</PMID>
  </reference>
  <verification_date>October 2022</verification_date>
  <study_first_submitted>June 15, 2020</study_first_submitted>
  <study_first_submitted_qc>June 15, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 18, 2020</study_first_posted>
  <last_update_submitted>October 31, 2022</last_update_submitted>
  <last_update_submitted_qc>October 31, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">November 2, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>University of Washington</investigator_affiliation>
    <investigator_full_name>Thomas Grabowski</investigator_full_name>
    <investigator_title>Professor, School of Medicine</investigator_title>
  </responsible_party>
  <keyword>mild cognitive impairment</keyword>
  <keyword>dementia</keyword>
  <keyword>tau</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Alzheimer Disease</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_description>De-identified tau PET scans will be shared with the National Alzheimer's Coordinating Center (NACC) through the Standardized and Centralized Alzheimer's Neuroimaging initiative (U24), which will make these data available under a data use agreement to non-commercial entities and non- commercial research projects.&#xD;
De-identified tau PET scans will be shared with Cerveau Technologies, Inc, for their own Imaging Core database of tau PET scans internationally, under terms of our Master Research Agreement. Non-identifying information about the participants, e.g. age, sex, apolipoprotein E (APOE) genotype, research diagnosis, is also to be included in the Cerveau imaging core database.</ipd_description>
    <ipd_info_type>Study Protocol</ipd_info_type>
    <ipd_info_type>Clinical Study Report (CSR)</ipd_info_type>
    <ipd_time_frame>tau PET imaging data will be uploaded to NACC within 6 months of data acquisition.&#xD;
tau PET imaging data will be uploaded to Cerveau Technologies, Inc within 6 months of data acquisition</ipd_time_frame>
    <ipd_access_criteria>per National Alzheimer's Coordinating Center policy&#xD;
per Cerveau Technologies, Inc policy</ipd_access_criteria>
    <ipd_url>http://www.alz.washington.edu</ipd_url>
  </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/NCT04437290
org study id: STUDY00009617
secondary id: P30AG066509
nct id: NCT04437290
lead sponsor: 
collaborator: 
collaborator: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
This is a cross-sectional, observational study that characterizes research participants with
      Alzheimer's disease (AD) for their patterns of brain degeneration with the investigational
      tau positron emission tomography (PET) radiotracer [18F] MK-6240. The goal is to describe the
      topographic pattern of involvement of cerebral brain regions (topographic phenotyping) in
      early stage AD participants using tau PET in a sub-cohort of the University of Washington
      Alzheimer's Disease Research Center (ADRC) Clinical Cohort, and to make this phenotype
      information available to affiliated research studies at the University of Washington and to
      the general scientific community via the National Alzheimer's Coordinating Center.
Memory loss and dementia, including Alzheimer's disease (AD), are heterogeneous in terms of
      pattern of symptoms and brain atrophy, likely due to underlying variability in AD biological
      processes, as well as comorbidity (separate diseases that co-occur with AD). The
      correspondence between clinical findings and underlying cause is imperfect, though, and the
      field has benefitted tremendously from development of biomarkers that can be used for
      diagnosis, for estimation of the biological burden of pathology, and/or for tracking disease
      trajectories. For example, in the National Institute on Aging-Alzheimer's Association
      (NIA-AA) research framework, biomarkers of Amyloid beta, phosphorylated Tau, and
      Neurodegeneration (A/T/N) standardize the separation of cases with Alzheimer pathophysiology
      from those without it.

      A sub-cohort of UW ADRC Clinical Core participants who have amyloid deposition (A+ by
      cerebrospinal fluid [CSF] or amyloid PET) and mild degrees of cognitive impairment will be
      investigated for their specific pattern of tau deposition with tau PET. Additionally,
      participants who are thought to be resilient to Alzheimer disease, e.g. 85 years or older and
      normal cognition, or A+ by CSF or amyloid PET and normal cognition, will also be investigated
      for their specific pattern of tau deposition with tau PET.

      The ADRC Imaging and Biomarker Core will conduct and analyze these scans, and store the data
      in the Integrated Brain Imaging Center at the University of Washington Medical Center campus,
      which is directed by the PI, Dr. Grabowski. It will also use other data collected by ADRC
      Cores (such as neuropsychology testing) to perform other analysis, such as estimating
      resilience measures (i.e. the ability of the brain to function well in spite of the presence
      of AD).

      This sub-cohort will aid in the investigation of Alzheimer's disease and related dementias
      (ADRD) by providing a means to better understand the relationships between the spatial
      patterns of tau deposition, neurodegeneration in the brain, cognitive symptoms, and
      resilience. It will provide a ready source of potential participants to the larger research
      community. By standardizing and supporting the collection imaging and CSF for research
      participants with Alzheimer's disease and related dementias under the ADRC, we promote
      research synergism and productivity across UW studies of AD and related disorders.
observational model: Cohort
time perspective: Prospective
measure: tau PET SUVR image
time frame: Day 1
description: Parametric [18F]MK6240 standardized uptake ratio images (SUVR) generated using an inferior cerebellar gray matter reference region.
arm group label: Alzheimer disease
description: The group is composed of individuals with a consensus diagnosis of amnestic mild cognitive impairment (MCI) or amnestic multimodal MCI or dementia primarily attributed to Alzheimer's disease (AD), as determined by the UW ADRC Clinical Core. They will have age of presentation > 55 years, sporadic onset, CDR (Clinical Dementia Rating Scale) score 0.5-1.0, and sufficient English competency to complete a standardized cognitive testing battery. All will have no contraindication to MRI and will have had an MRI scan in the UW ADRC Imaging and Biomarker Core. These participants will undergo PET scanning with the investigational tau tracer [18F] MK6240
intervention type: Drug
intervention name: investigational radiotracer [18F]MK6240
description: Brain PET scan
arm group label: Alzheimer disease
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 55 Years
maximum age: N/A
healthy volunteers: No
last name: Thomas J Grabowski, MD
role: Principal Investigator
affiliation: University of Washington
last name: Christina Caso
phone: 206-221-9038
email: cdcaso@uw.edu
last name: Annika Noreen, PhD
phone: 206-685-1221
email: annikn@uw.edu
citation: Lohith TG, Bennacef I, Vandenberghe R, Vandenbulcke M, Salinas CA, Declercq R, Reynders T, Telan-Choing NF, Riffel K, Celen S, Serdons K, Bormans G, Tsai K, Walji A, Hostetler ED, Evelhoch JL, Van Laere K, Forman M, Stoch A, Sur C, Struyk A. Brain Imaging of Alzheimer Dementia Patients and Elderly Controls with 18F-MK-6240, a PET Tracer Targeting Neurofibrillary Tangles. J Nucl Med. 2019 Jan;60(1):107-114. doi: 10.2967/jnumed.118.208215. Epub 2018 Jun 7.
PMID: 29880509
citation: Pascoal TA, Shin M, Kang MS, Chamoun M, Chartrand D, Mathotaarachchi S, Bennacef I, Therriault J, Ng KP, Hopewell R, Bouhachi R, Hsiao HH, Benedet AL, Soucy JP, Massarweh G, Gauthier S, Rosa-Neto P. In vivo quantification of neurofibrillary tangles with [18F]MK-6240. Alzheimers Res Ther. 2018 Jul 31;10(1):74. doi: 10.1186/s13195-018-0402-y.
PMID: 30064520
citation: Koole M, Lohith TG, Valentine JL, Bennacef I, Declercq R, Reynders T, Riffel K, Celen S, Serdons K, Bormans G, Ferry-Martin S, Laroque P, Walji A, Hostetler ED, Briscoe RJ, de Hoon J, Sur C, Van Laere K, Struyk A. Preclinical Safety Evaluation and Human Dosimetry of [18F]MK-6240, a Novel PET Tracer for Imaging Neurofibrillary Tangles. Mol Imaging Biol. 2020 Feb;22(1):173-180. doi: 10.1007/s11307-019-01367-w.
PMID: 31111397
responsible party type: Principal Investigator
investigator affiliation: University of Washington
investigator full name: Thomas Grabowski
investigator title: Professor, School of Medicine
mesh term: Alzheimer Disease
sharing ipd: Yes
ipd description: De-identified tau PET scans will be shared with the National Alzheimer's Coordinating Center (NACC) through the Standardized and Centralized Alzheimer's Neuroimaging initiative (U24), which will make these data available under a data use agreement to non-commercial entities and non- commercial research projects.
De-identified tau PET scans will be shared with Cerveau Technologies, Inc, for their own Imaging Core database of tau PET scans internationally, under terms of our Master Research Agreement. Non-identifying information about the participants, e.g. age, sex, apolipoprotein E (APOE) genotype, research diagnosis, is also to be included in the Cerveau imaging core database.
ipd info type: Study Protocol
ipd info type: Clinical Study Report (CSR)
ipd time frame: tau PET imaging data will be uploaded to NACC within 6 months of data acquisition.
tau PET imaging data will be uploaded to Cerveau Technologies, Inc within 6 months of data acquisition
ipd access criteria: per National Alzheimer's Coordinating Center policy
per Cerveau Technologies, Inc policy
ipd url: http://www.alz.washington.edu