A Non-drug Methods Study in Participants With Alzheimer's Disease
Condition: Alzheimer's Disease
MeSH terms: Alzheimer Disease
Intervention: PET scan using florbetapir; MRI Scan
Intervention description: A single intravenous microdose of 260 MBq (7 mCi) 18F-AV-45 (florbetapir F 18) will be administered.; Three different measurements will be taken: volumetric MRI (vMRI), diffusion tensor imaging (DTI), and resting state functional MRI (rsfMRI). In addition, radiological MRI scans will be taken to monitor vasogenic edema and microhemorrhages.
Phase: Phase 1
Study type: Interventional
Primary purpose: Basic Science
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 56.0
Sex: All
Minimum age: 55 Years
Healthy volunteers: No
Keywords: Mild Cognitive Impairment; Brain Imaging Biomarkers; Magnetic resonance imaging biomarker; Positron Emission Tomography

Summary:

      This study will investigate the volume, function and composition of the brain using magnetic
      resonance imaging (MRI) and positron emission tomography (PET) scanning technology in
      participants with memory complaints or early signs of Alzheimer's pathology.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Present with prodromal Alzheimer's Disease (AD) or mild AD based on the disease
             diagnostic criteria

          -  Are men or post-menopausal women, at least 55 years of age. Post-menopausal women are
             defined as women who have had a hysterectomy and/or bilateral oophorectomy; or who
             have been amenorrheic for at least 2 years

          -  Have a caretaker/study informant who provides a separate written informed consent to
             participate. If a caretaker/study informant cannot continue, one replacement is
             allowed

          -  Gradual and progressive change in memory function reported by participants or
             informants over more than 6 months

          -  Objective evidence of significantly impaired episodic memory characteristic of
             hippocampal dysfunction on testing: Free and Cued Selective Reminding Test (FCSRT):
             less than or equal to (≤) 16 for free recall or ≤ 40 for total recall. Protocol
             amendment: FCSRT ≤ 24 for free recall or ≤ 44 for total recall

          -  Clinical Dementia Rating (CDR) equals 0.5 or 1, Memory box score greater than or equal
             to 0.5

          -  Mini Mental Scale Examination (MMSE) 20-30. Protocol amendment: MMSE 23-30, inclusive

          -  Positive florbetapir F 18 scan

          -  Participants must meet all of the Disease Diagnostic Criteria to be considered for
             enrollment

        Exclusion Criteria:

          -  Diagnosis or history of other possible etiology of dementia, including but not limited
             to other neurodegenerative disorders

          -  Frontotemporal dementia, Lewy body disease, vascular dementia, Huntington's Disease or
             concomitant Parkinson's disease, progressive supranuclear palsy (PSNP) or other
             movement disorder

          -  Has B12 <200 pg/L or folate <7.5 nmol/L indicating vitamin deficiency

          -  Has a history within the past 5 years of a serious infectious disease affecting the
             brain, including meningitis, or encephalitis

          -  Significant history of alcoholism or substance abuse (at the judgment of the
             investigator)

          -  Severe or recurrent head injury that is clinically relevant to the disease under
             study, (that is, with permanent neurological/cognitive sequelae)

          -  Onset of dementia following heart surgery or cardiac arrest

          -  Diagnosis or history of cerebrovascular disease (for example, stroke, transient
             ischemic attack), severe carotid stenosis, cerebral hemorrhage, intracranial tumor,
             subarachnoid hemorrhage, or subdural hematoma that could contribute to the subject's
             current cognitive or functional status, impair ability to fully participate in the
             trial or that may impact status

          -  Has had a Positron Emission Tomography (PET) within 6 months of the scheduled imaging
             follow-up

          -  Greater than 4 cerebral microhemorrhages (CMH) on T2* -weighted gradient-recalled echo
             sequences (regardless of their anatomical or diagnostic characterization as "possible"
             or "definite"), a single area of superficial siderosis, or prior evidence of
             macrohemorrhage

          -  Any indications of severe deep white matter lesions or vasogenic edema that present as
             hyperintense regions on the Fluid Attenuated Inversion Recovery (FLAIR) sequence, or
             other clinically relevant findings observed on the Magnetic Resonance Imaging (MRI)
             scans

          -  Specific exclusionary brain MRI findings, as determined by the investigator in
             consultation with the sponsor, that could either contribute to the participant's
             current cognitive or functional decline impair ability to fully participate in the
             trial or that may impact status during the trial (for example, brain tumors or other
             non-vascular structural abnormalities like hydrocephalus)

          -  History within the past 5 years of a primary or recurrent malignant disease with the
             exception of resected cutaneous squamous cell carcinoma in situ, basal cell carcinoma,
             cervical carcinoma in situ, or in situ prostate cancer with a normal prostate-specific
             antigen (PSA) post resection

          -  History of clinically significant cardiovascular or renal events

          -  Diastolic blood pressure of 95 or more and systolic blood pressure of 160 or more in
             sitting position after at least 5 minutes of rest

          -  Any history of seizure

          -  History of clinically significant head trauma or clinically significant unexplained
             loss of consciousness within the last 5 years (as determined by the investigator in
             consultation with the Sponsor)

          -  A current Axis I diagnosis of major depressive disorder or other psychiatric illness
             (Diagnostic and Statistical Manual Revised Fourth Edition [DSM-IV-TR]) criteria per
             the investigator's judgment. (Note: Participants on a stable antidepressant and/or
             anxiolytic treatment may participate.)

          -  Having suicidal ideations, or attempted suicide in the past 15 years

          -  History of schizophrenia, bipolar disorder, or other severe mental illness

          -  Known history of alcohol or drug abuse (as defined by the DSM-IV-TR) within 5 years
             prior to enrolling or a positive result regarding use of illicit drugs on the drug
             screening test

          -  Chronic hepatic diseases as indicated by liver function test abnormalities (alanine
             trasaminase [ALT], aspartate transaminase [AST], bilirubin, or gamma-glutamyl
             transferase [GGT] above 2 times upper limit of normal), positive serology for
             Hepatitis B or C, or other manifestations of liver disease

          -  Has compromised renal function at screening, as determined by creatinine clearance <30
             mL/min based on Cockcroft-Gault calculation of creatinine clearance

          -  History of asthma, chronic obstructive pulmonary disease, or other chronic respiratory
             conditions

          -  Known positive human immunodeficiency virus (HIV) status, history of syphilitic
             infection

          -  A clinically significant abnormality in the 12-lead electrocardiograms (ECG),
             including complete heart block, bradycardia (heart rate <50 beats/minute), tachycardia
             (heart rate ≥95 beats/minute), sinus pauses >2 seconds, second or third degree heart
             block, QTc >450 msec for males or QTc >470 for females

          -  Treatment with an investigational small molecule within 1 year preceding the first
             study period, or participation in a trial with active or passive immunization against
             amyloid if participant was assigned to the active treatment arm

          -  Fulfillment of any contraindications to a 3T magnetic resonance imaging (MRI) scan
             (for example, subjects with non-removable ferromagnetic implants (such as cardiac
             pacemaker), aneurysm clips or other foreign bodies, or subjects with claustrophobic
             symptoms that would contraindicate an MRI scan)

          -  Sensitivity to florbetapir F 18

          -  Are not capable of swallowing whole oral medications

          -  Abnormal thyroid function

               -  Thyroid stimulating hormone (TSH) values are outside of the normal range 0.3-5.6
                  mIU/L. (NOTE: Participants with stable treatment of hypothyroidism and with
                  normal value of TSH will be allowed to enter the study)