The Aging Brain and Cognition: Contribution of Vascular Injury, Amyloid Plaque and Tau Protein to Cognitive Dysfunction After Stroke

Chang Gung Medical Foundation

Status and phase: Completed; Phase 2

Conditions: Vascular Mild Cognitive Impairment; Post-stroke Dementia

Treatments: Drug: AV-45; Drug: THK-5351

Study type: Interventional

Funder types: Other

Identifiers

NCT04588649

103-7584A

Details and patient eligibility

About

Stroke can lead to signficiant neurological deficits, and about one-third of stroke patients will be diagnosed of vascular mild cognitive impairment or post-stroke dementia. Post-stroke dementia includes all types of dementia that happen after stroke, irrespective of their cause, and vascular dementia (VaD), degenerative dementia (especially Alzheimer's disease), or mixed dementia (dementia as a result of the coexistence of vascular lesions of the brain and neurodegenerative lesions) are the most common causes of post-stroke dementia. However, it is difficult to determine to what extent cognitive impairment may be attributable to stroke versus concomitant Alzheimer disease. With the advent of PET imaging technique, we are able to conduct a multi-modal neuroimaging study to explore the composite influence of vascular injury, amyloid plaque and Tau protein the the cognitive performance after stroke.

Enrollment: 181 patients

Sex: All

Ages: 50+ years old

Volunteers: Accepts Healthy Volunteers

Inclusion criteria

Inclusion criteria for stroke/TIA patients

• Males or females with age >= 50 years old
• Having cerebral stroke or transient ischemic attack
• Modified Rankin Scale < 4
• Ability to participate in cognitive and neuroimaging assessments
• Female subjects of childbearing potential must practice effective contraception during the study and be willing and able to continue contraception after the final study
• Provision of signed informed consent

Inclusion criteria for healthy elderly controls

• Males or females with age >= 50 years old
• Without history of cerebral stroke or transient ischemic attack
• Ability to participate in cognitive and neuroimaging assessments
• Female subjects of childbearing potential must practice effective contraception during the study and be willing and able to continue contraception after the final study
• Provision of signed informed consent

Exclusion criteria

Exclusion criteria for all subjects

• Presence of dementia diagnosis before the index stroke or at the initial screening History of vascular MCI (VaMCI)
• The Chinese version of the Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE) score >=104 [24] at the initial screening.
• Presence of large infarction or lobar encephalomalacia on brain CT or MRI.
• Severe language impairment precluding cognitive assessments, defined as a score of 3 points in the language score of the National Institute of Health Stroke Scale.
• Life expectancy less than 1 year.
• Clinically significant abnormal laboratory values.
• Clinically significant or unstable medical or psychiatric illness.
• Epilepsy history.
• Cognitive impairment resulting from trauma or brain damage.
• Substance abuse or alcoholism in the past 1 year
• General MRI, and / or PET exclusion criteria.
• Pregnant or becoming pregnant during the study (as documented by pregnancy testing at screening or at any date during the study according to the PI discretion) or current breast feeding.
• History of allergy to 18F-labelled radionucleic agents, [18F]AV-45 or [18F]THK-5351.
• Subjects having high risks for the study according to the PI discretion.

Trial design

Primary purpose: Diagnostic

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: Single Blind

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181 participants in 2 patient groups

THK-5351

Other group

Description:

Name: \[18F\]THK5351，(S)-6-\[(3-Fluoro-2-hydroxy)propoxy\]-2-(2-Methylaminopyrid-5-yl)-quinoline Dosage form: intravenous injection Dose(s): 10mCi Dosing schedule: Visit 2 Mechanism of action (if known): high affinity radiotracer for the tau protein Pharmacological category：Radio pharmaceutical

Treatment:

Drug: AV-45

Drug: THK-5351

AV-45

Other group

Description:

Name: \[18F\]AV-45, (E)-4-(2-(6-(2-(2-(2-\[18F\]fluoroethoxy) ethoxy) ethoxy)pyridin-3-yl)vinyl)-N-methylbenzenamine Dosage form: intravenous injection Dose(s): 10mCi Dosing schedule: Visit 2 Mechanism of action (if known): high affinity radiotracer for the β- amyloid protein Pharmacological category：Radio pharmaceutical

Treatment:

Drug: AV-45

Drug: THK-5351