Alzheimer Disease
Conditions
Keywords
Tau, neurodegeneration, positron emission tomography
Brief summary
This is a study to evaluate biodistribution, pharmacokinetics and safety of \[18F\]THK-5351 positron emission computed tomography in Cognitively Healthy Subjects and Patients with Alzheimer's Disease.
Detailed description
This is a study to evaluate biodistribution, pharmacokinetics and safety of \[18F\]THK-5351 positron emission computed tomography. Ten cognitively healthy subjects and 10 patients with Alzheimer's Disease will be enrolled. The primary outcome measures are to evaluate pharmacokinetics of \[18F\]THK-5351 Positron Emission Tomography imaging . Tracer biodistribution will be evaluated by global and regional standardized uptake value ratio of \[18F\]THK-5351 in the brain. Safety. For safety assessment, a physical examination, Electrocardiogram and vital signs will be performed at baseline and at the completion of all imaging to assess for interval change.
Interventions
DRUG[18F]THK-5351
Imaging for evaluating the biodistribution, pharmacokinetics and safety of abnormal tau protein in the brain
Sponsors
Asan Foundation
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
DIAGNOSTIC
Masking
SINGLE (Investigator)
Eligibility
Sex/Gender
ALL
Age
20 Years to 80 Years
Healthy volunteers
Yes
Inclusion criteria
; \- General Subject Inclusion Criteria In order to be eligible for participation in this trial, the subject must: 1. Be able to read at a 6th grade level or equivalent, (as determined by the investigator, and must have a history of academic achievement and/or employment sufficient to exclude mental retardation.) 2. Be able to speak, read, hear, and understand the language of the trial staff, and the informed consent form, and possess the ability to respond verbally to questions, follow instructions, and complete questionnaires and detailed neuropsychological test. 3. Have results of clinical laboratory tests/physical examination, vital signs, and Electrocardiogram within normal limits (at 45 days prior to \[18F\]THK-5351 Positron Emission Tomography scan ) or clinically acceptable to the investigator at screening. 4. Be able to possess the ability to respond verbally to questions, follow instructions, and underwent research assessment, including brain images based on the investigator's judgment. Each subject is also able and willing to adhere visit schedules. 5. If female, not be of childbearing potential as indicated by one of the following 1. has reached natural menopause, defined as ≥ 24 months of spontaneous amenorrhea or 2. has had a hysterectomy; or 3. has had a bilateral oophorectomy (with or without a hysterectomy) and more than 6 weeks have passed since the surgery. 6. Each subject (or legal representative) must sign the informed consent form in accordance with local requirements after the scope and nature of the investigation have been explained to them, and before screening assessments. \- Normal Subject Inclusion Criteria <!-- --> 1. . Be ≥ 20 years of age at the screening visit 2. Each subject must not report a history of memory decline with gradual onset and slow progression, that is either corroborated by an informant who knows the subject well or is documented in medical records. Each subject must have general cognitive function and activities of daily living sufficiently intact, based on clinical assessment, so as not to meet criteria for mild AD dementia (based on DSM-IV-TR(Diagnostic and Statistical Manual of Mental Disorders, 4th Edition) and NINCDS-ADRDA(National Institute of Neurological and Communicative Disorders and Stroke; Alzheimer's Disease and Related Disorders Association) criteria). 3. Each subject must have results of Korean-Mini Mental State Exam (K-MMSE) at screening that is ≥1.5 SD above the appropriate population mean, corrected age and education. 4. Each subject must not have objective impairment in memory at screening that is ≥1.5 SD above the appropriate population mean, corrected age and education, as measured by the Seoul Verbal Learning Test (SVLT) delayed recall score of the Seoul Neuropsychological Screening Battery (SNSB)-Ⅱ. 5. Each subject must have normal level of general cognitive function and activities of daily living sufficiently intact, that is 0 score as measured by the Clinical Dementia Rating (CDR). 6. Each subject must have an MRI scan obtained at screening that supports diagnosing the current status of normal cognition. The MRI for research must be consistent and sufficient in quality enough to analyze volume of interest (VOI) with partial volume correction (Detailed protocol is described in the MRI scanning manual). 7. Each subject must be willing to provided blood samples for genotyping apolipoprotein E. * Alzheimer's Disease Inclusion Criteria <!-- --> 1. Be ≥ 50 and \< 80 years of age at the Screening Visit. 2. Each subject must have general cognitive function and activities of daily living impairment, based on clinical assessment, so as to meet criteria for AD dementia (based on DSM-IV-TR and NINCDS-ADRDA criteria). 3. Each subject's K-MMSE score ranges 15-26 and CDR 0.5, 1 or 2. 4. Each subject must have a Rosen-modified Hachinski Ischemia Score ≤ 4 at Screening. 5. Each subject must have a reliable and competent trial partner/informant who must have a close relationship with the subject, and can be accompanied at all visits in this study. 6. Each subject must have an MRI scan obtained at screening that supports diagnosing Alzheimer's disease. The MRI for research must be consistent and sufficient in quality enough to analyze volume of interest (VOI) with partial volume correction (Detailed protocol is described in the MRI scanning manual). 7. If receiving some medications, be on a stable dose for at least the 4 weeks before performing THK5351 PET scan, and the subject must be willing to remain on the same dose for the duration of the trial. 8. Each subject must be willing to provided blood samples for genotyping ApoE. 9. Each subject must shows positive in amyloid PET scan.
Exclusion criteria
The subject must be excluded from participating in the trial if the subject fulfil any single criteria described below: * General
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Pharmacokinetics: Maximum Serum Concentration (Cmax) of [18F]THK-5351 | 0-90 minutes post injection | Compare time activity curve and calculate maximum serum concentration (Cmax) of each region of interest of \[18F\]THK-5351 positron emission computed tomography in cognitively healthy subjects and patients with Alzheimer's disease |
| Assess global and regional tau deposition as measured by standard uptake value ratio (SUVR) of [18F]THK-5351 | 0-90 minutes post injection or 50-70 minutes post injection | Compare Standard uptake value ratio (SUVR) and distribution of \[18F\]THK-5351 in cognitively healthy subjects and patients with Alzheimer's disease |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Correlation between standard uptake value ratio (SUVR) and distribution volume of ratio(DVR) of [18F]THK-5351 positron emission computed tomography | 0-90 minutes post injection or 50-70 minutes post injection | We will evaluate correlation between standard uptake value ratio (SUVR) and distribution volume of ratio(DVR) of\[18F\]THK-5351 positron emission computed tomography |
| Optimal scanning time for brain imaging using F-18 THK-5351. | 0-90 minutes post injection | PET data will be acquired during a 90-min dynamic brain PET scan and will be started simultaneously with the injection of 10mCi of F-18 THK-5351. Reconstruction of PET imaging with several time frame will be compared. |
| Concentrations of metabolite in plasma of [18F]THK-5351 | 0-90 minutes post injection or 50-70 minutes post injection | Plasma metabolite concentrations \[18F\]THK-5351 will be assessed. |
| Number of participants with treatment related adverse events as a measure of safety | 0-90 minutes post injection or 50-70 minutes post injection | For safety assessment, a physical examination, EKG and vital signs will be performed at baseline and at the completion of all imaging to assess for interval change. |
Countries
South Korea
Outcome results
None listed