Clinical trial NCT02656498: [18F]THK-5351 Positron Emission Computed Tomography Study of Normal, Mild Cognitive Impairment, Alzheimer's Disease and Other Neurodegenerative Disease
Official title: An Open Label, Multicenter Study for Evaluation of the Clinical Utility of [18F]THK-5351 Positron Emission Computed Tomography in Cognitively Healthy Volunteers, Subjects With Mild Cognitive Impairment, Subjects With Alzheimer's Disease and Subjects With Other Neurodegenerative Diseases
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Alzheimer's Disease
Mild Cognitive Impairment
Neurodegenerative Diseases
Keywords: Tau, neurodegeneration, positron emission computed tomography
Lead sponsor: Asan Medical Center
Sponsor class: OTHER
Collaborators: name: Korea Health Industry Development Institute
name: Samsung Medical Center
First posted: 2016-01-15
Enrollment: 135
Sex: ALL
Minimum age (years): 40
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: DIAGNOSTIC

Brief summary: This is a cross-sectional and longitudinal study to evaluate the clinical utility of \[18F\]THK-5351 positron emission computed tomography in cognitively healthy volunteers, mild cognitive impairment (MCI), Alzheimer's disease (AD) and other neurodegenerative patients.


Eligibility criteria: Inclusion Criteria:

1. General Subject Inclusion Criteria

   In order to be eligible for participation in this trial, the subject must:
   * Be ≥ 40 and \< 80 years of age at the Screening Visit.
   * 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.)
   * 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.
   * Have results of clinical laboratory tests/physical examination, vital signs, and ECG within normal limits (at 90 days prior to \[18F\]THK-5351 positron emission computed tomography) or clinically acceptable to the investigator at screening.
   * 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.
   * If female, not be of childbearing potential as indicated by one of the following
   * 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.
   * Each subject must be willing to provided blood samples for genotyping apolipoprotein E
2. Cognitively Healthy Subjects
3. MCI Subjects
4. AD Subjects
5. Subjects with other neurodegenerative disease

Exclusion Criteria

The subject must be excluded from participating in the trial if the subject fulfil any single criteria described below:

1. General Exclusion Criteria

* Based on the investigators' judgement, if the patient is not capable of communicating with the site personnel, if the patient is not proficient in the language in which the psychometric tests will be completed, or if the patient is not sufficient for compliance with the study procedures.
* The patient has an abnormal physical examination or abnormal laboratory test results at the screening that are clinically significant to affect results of the research, as judged by the investigator.
* If the patient has or is suspicious of having a hypersensitivity or allergy to \[18F\] THK-5351 or its derivatives.
* The patient is pregnant, is attempting to become pregnant, or is nursing (breast-feeding) children.
* The patient has a history of alcoholism or drug dependency/abuse within the last 2 years before screening.
* The patient has contraindications to undergo positron emission computed tomography or MRI, which include but are not restricted to the examples below: claustrophobia, cardiac pacemaker, metal devices around the eye or spinal cord, cochlear implant, etc.) at the screening visit.
* The patient has been treated with any investigational medicinal product (IMP) within 30 days prior to the screening visit.
* The patient has been tested positive for hepatitis B surface antigen (HBsAg), hepatitis C virus antibodies (anti-HCV), HIV Antibody, or syphilis serum test at the screening visit.
* The patient has been receiving an anti-cholinergic drug in a regular basis within 3 months prior to the screening visit.
* The patient has evidence of a clinically relevant neurological disorders other than the disease being studied (i.e., prodromal AD) at screening, including but not limited to: territorial cerebral infarction, intracranial hemorrhage, multiple sclerosis, neurosyphilis, mental retardation, hypoxic encephalopathy, major head trauma with loss of consciousness that led to persistent cognitive deficits.

Primary outcomes:
measure: Cross-sectional [18F]THK-5351 Imaging Results
timeFrame: 50-70 minutes post injection
measure: Assess the rate of change of tau deposition as measured by [18F]THK-5351 uptake (SUVR) over time
timeFrame: 24 months
Secondary outcomes:
measure: Correlation between standard uptake value ratio (SUVR) of [18F]THK-5351 positron emission computed tomography and neuropsychiatric test scores
timeFrame: 50-70 minutes post-injection
measure: Correlation between standard uptake value ratio (SUVR) of [18F]THK-5351 positron emission computed tomography and indices of structural MRI
timeFrame: 50-70 minutes post-injection
measure: Correlation between standard uptake value ratio (SUVR) of [18F]THK-5351 positron emission computed tomography and indices of functional MRI
timeFrame: 50-70 minutes post-injection
measure: Correlation between standard uptake value ratios (SUVR) and distribution of [18F]THK-5351 positron emission computed tomography and amyloid positron emission computed tomography
timeFrame: 50-70 minutes post-injection
Other outcomes:
Locations:
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center
Study officials:
affiliation: Asan Medical Center
name: Jae Seung Kim, M.D.,Ph.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Chun MY, Lee J, Jeong JH, Roh JH, Oh SJ, Oh M, Oh JS, Kim JS, Moon SH, Woo SY, Kim YJ, Choe YS, Kim HJ, Na DL, Jang H, Seo SW. 18F-THK5351 PET Positivity and Longitudinal Changes in Cognitive Function in beta-Amyloid-Negative Amnestic Mild Cognitive Impairment. Yonsei Med J. 2022 Mar;63(3):259-264. doi: 10.3349/ymj.2022.63.3.259.
citation: Park JE, Yun J, Kim SJ, Shim WH, Oh JS, Oh M, Roh JH, Seo SW, Oh SJ, Kim JS. Intra-individual correlations between quantitative THK-5351 PET and MRI-derived cortical volume in Alzheimer's disease differ according to disease severity and amyloid positivity. PLoS One. 2019 Dec 13;14(12):e0226265. doi: 10.1371/journal.pone.0226265. eCollection 2019.