A Longitudinal Evaluation of a Radiotracer for Use in Tau Tracking
Condition: Alzheimer Disease; Mild Cognitive Impairment
MeSH terms: Alzheimer Disease; Cognitive Dysfunction
Intervention: All Subjects
Intervention description: All subjects will be given the experimental tau PET radioligand [18F]MK-6240
Phase: Phase 2
Study type: Interventional
Primary purpose: Diagnostic
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 27.0
Sex: All
Minimum age: 50 Years
Maximum age: 85 Years
Healthy volunteers: Accepts Healthy Volunteers

Summary:

      This is a longitudinal, observational study evaluating the imaging characteristics of the tau
      PET radioligand [18F]MK-6240 in Alzheimer's disease (AD), Mild Cognitive Impairment (MCI) and
      Healthy Volunteer (HV) subjects. Up to 42 subjects, including approximately 28 MCI/mild AD
      subjects, up to 5 moderate AD subjects, and 9 similarly aged HV subjects will be consented
      and screened. Imaging procedures include [11C]PiB to evaluate amyloid deposition,
      [18F]MK-6240 PET, and structural MRI. All subjects complete an evaluable baseline
      [18F]MK-6240 PET scan, as well as scans at 6, 12 and 24 months post-baseline. If unable to
      complete the 6 month, 12 month, or 24 month visit, an 18 month and/or 30 month visit may
      instead be scheduled, totaling a maximum of four time points.
    

Eligibility criteria:

        Inclusion Criteria for all subjects:

          -  Signed and dated written informed consent must be obtained from the subject to enter
             the study and before any assessment is performed.

          -  Pregnancy: Participant is not pregnant at the time of the PET and MRI imaging exams.
             Urine pregnancy tests will be conducted as needed with pre-menopausal women who are of
             child-bearing potential.

          -  Willing and able to undergo study procedures and study schedule

          -  Availability of a study partner who has frequent and sufficient contact with the
             subject and is able to provide accurate information regarding the subject's cognitive
             and functional abilities for the CDR, agrees to accompany the subject and provide
             information at visits or is available by phone. The study partner must have sufficient
             cognitive capacity, in the judgment of the investigator, to accurately report upon the
             subject's behavior and cognitive and functional abilities.

          -  Healthy with no clinically relevant finding on physical examination at screening and
             upon reporting for the Baseline [18F]MK-6240 imaging visit.

        Inclusion Criteria for Healthy Volunteers

          -  Normal Cognition based on cognitive results at screening.

          -  Healthy with no clinically relevant finding on physical examination at screening and
             upon reporting for the Baseline [18F]MK-6240 imaging visit.

          -  CDR global score =0

        Inclusion Criteria for Subjects with a Diagnosis of MCI or Dementia Due to AD

          -  Have screening [11C]PiB PET imaging demonstrating amyloid binding based on qualitative
             read or DVR index value >1.20.

          -  MMSE score 26-30 (inclusive), CDR global score 0.5 for subjects with MCI

          -  MMSE score 22-26 (inclusive), CDR global score 0.5 or 1 for subjects with mild
             dementia due to AD

          -  MMSE score 16-21 (inclusive), CDR global score 1-2 for subjects with moderate dementia
             due to AD

          -  Subjects with MCI must meet 2018 research criteria for MCI (Jack et al., 2018).

          -  Subjects with dementia must meet 2018 research criteria for dementia (Jack et al.,
             2018).

          -  A structural brain MRI with no evidence of non-AD disease to account for dementia or
             MRI exclusion criteria.

        Exclusion Criteria for all subjects

          -  Lack of capacity to provide informed consent at study entry.

          -  Subject has received an investigational drug or device within 30 days of screening.
             Other experimental PET radiotracer drugs are not excluded.

          -  For women, pregnant, lactating or breastfeeding or intention to become pregnant.

          -  Evidence of unstable or untreated clinically significant gastrointestinal,
             cardiovascular, hepatic, renal, hematological, neoplastic, endocrine, alternative
             neurological, immunodeficiency, pulmonary, or other disorder or disease. Stable,
             treated chronic medical conditions like hypertension, hypercholesterolemia, diabetes
             mellitus, non-metastatic dermatologic or prostatic cancer, etc. are acceptable as long
             as they do not, in the study investigator's opinion, contribute to cognitive
             dysfunction or limit participation in study procedures.

          -  Any illness or other consideration that makes it unlikely that the subject will be
             able to complete the 26-month study.

          -  Current or prior history (within past 5 years) of significant alcohol or substance
             abuse as determined by the investigator.

          -  Psychiatric disorders that may interfere with the study including current major Axis I
             DSM-V disorders including but not limited to severe Major depression, current or
             history of bipolar I disorder, or schizophrenia.

          -  Non-English speakers or subjects who are unable to comprehend study materials are
             excluded at entry

          -  MRI exclusion criteria include: Findings that may be responsible for neurologic status
             of the subject such as significant evidence of cerebrovascular disease with multiple
             infarcts, infectious disease, space-occupying lesion, normal pressure hydrocephalus,
             CNS trauma, or any other structural abnormality that may impact cognition or image
             analysis, as judged by the investigator.

          -  MRI-incompatible implants or devices such as certain cardiac pacemakers or
             defibrillators, insulin pumps, cochlear implants, metallic ocular foreign body,
             implanted neural stimulators, CNS aneurysm clips and other medical implants that have
             not been certified for MRI, or history of claustrophobia in MRI that prevents
             completion of MRI protocol.

          -  Treatment with any therapeutic molecule that targets Aβ or tau within 12 months prior
             to screening.