[18F]THK-5351 Positron Emission Computed Tomography Study of Normal, Mild Cognitive Impairment, Alzheimer's Disease and Other Neurodegenerative Disease

NCT02656498 | Completed Phase 2

• 1 other identifier: THK-15002
• Study Type: interventional
• Target: 135
• Locations: 1 country
• Sites: 2

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.

Conditions

Alzheimer's Disease; Mild Cognitive Impairment; Neurodegenerative Diseases

Keywords

Tau, neurodegeneration, positron emission computed tomography

Outcome Measures

Primary Outcomes (2)

• Cross-sectional [18F]THK-5351 Imaging Results

  Compare Standard uptake value ratio (SUVR) and distribution of \[18F\]THK-5351 in subjects with MCI, subjects with AD, subjects with other neurodegenerative disease and cognitively healthy individuals.

  50-70 minutes post injection

• Assess the rate of change of tau deposition as measured by [18F]THK-5351 uptake (SUVR) over time

  Compare Standard uptake value ratio (SUVR) and distribution of \[18F\]THK-5351 in subjects with MCI, subjects with AD, subjects with other neurodegenerative disease and cognitively healthy individuals.

  24 months

Secondary Outcomes (4)

• Correlation between standard uptake value ratio (SUVR) of [18F]THK-5351 positron emission computed tomography and neuropsychiatric test scores

  50-70 minutes post-injection

• Correlation between standard uptake value ratio (SUVR) of [18F]THK-5351 positron emission computed tomography and indices of structural MRI

  50-70 minutes post-injection

• Correlation between standard uptake value ratio (SUVR) of [18F]THK-5351 positron emission computed tomography and indices of functional MRI

  50-70 minutes post-injection

• Correlation between standard uptake value ratios (SUVR) and distribution of [18F]THK-5351 positron emission computed tomography and amyloid positron emission computed tomography

  50-70 minutes post-injection

Study Arms (4)

Cognitively Healthy Subjects

EXPERIMENTAL

Cognitively healthy subjects will receive an IV injection, \[18F\]THK-5351 at baseline and also receive an IV injection, \[18F\]THK-5351 at 24 months.

Drug: [18F]THK-5351

MCI Subjects

EXPERIMENTAL

MCI Subjects will receive an IV injection, \[18F\]THK-5351 at baseline and also receive an IV injection, \[18F\]THK-5351 at 24 months.

Drug: [18F]THK-5351

AD Subjects

EXPERIMENTAL

AD Subjects will receive an IV injection, \[18F\]THK-5351 at baseline and also receive an IV injection, \[18F\]THK-5351 at 24 months.

Drug: [18F]THK-5351

Subjects with other neurodegenerative disease

EXPERIMENTAL

Subjects with other neurodegenerative disease will receive an IV injection, \[18F\]THK-5351 at baseline.

Drug: [18F]THK-5351

Interventions

[18F]THK-5351 DRUG

Imaging for evaluating the accumulation of abnormal tau protein in the brain

Also known as: FluoroTau

AD Subjects; Cognitively Healthy Subjects; MCI Subjects; Subjects with other neurodegenerative disease

Eligibility Criteria

• Age: 40 Years - 80 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• Cognitively Healthy Subjects
• MCI Subjects
• AD Subjects
• Subjects with other neurodegenerative disease

You may not qualify if:

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

Sponsors & Collaborators

• Jae Seung Kim: lead
• Korea Health Industry Development Institute: collaborator
• Samsung Medical Center: collaborator

Study Sites (2)

Asan Medical Center

Seoul, 05505, South Korea

Location

Samsung Medical Center

Seoul, South Korea

Location

Related Publications (2)

• 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.

  PMID: 35184428 DERIVED

• 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.

  PMID: 31834916 DERIVED

MeSH Terms

Conditions

Alzheimer Disease; Cognitive Dysfunction; Neurodegenerative Diseases; Pick Disease of the Brain; Nerve Degeneration

Interventions

THK5351

Condition Hierarchy (Ancestors)

Dementia; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Tauopathies; Neurocognitive Disorders; Mental Disorders; Cognition Disorders; Frontotemporal Dementia; Frontotemporal Lobar Degeneration; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Jae Seung Kim, M.D.,Ph.D.

  Asan Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: January 12, 2016
• First Posted: January 15, 2016
• Study Start: January 11, 2016
• Primary Completion: December 31, 2019
• Study Completion: December 31, 2019
• Last Updated: December 14, 2020

Record last verified: 2020-12

Locations

KR (2)