The Influence of Sequential Tau Protein and Amyloid Plaque Imaging Changes on Stroke Prognosis and Cognitive Outcome

Chang Gung Medical Foundation

Status and phase: Enrolling; Phase 2

Conditions: Post-stroke Dementia, Vascular Mild Cognitive Impairment

Treatments: Drug: [18F]AV-45; Drug: [18F]THK-5351

Study type: Interventional

Funder types: Other

Identifiers

NCT04572477

201601675A0

Details and patient eligibility

About

Amyloid plaques and tau protein are the landmarks of neurodegeneration in Alzheimer's disease (AD). On the other hand, it is reported that cerebral ischemia may induce amyloid plaques and tau protein accumulation. However, it was difficult to in vivo disentangle the complex and dynamic interactions between AD pathophysiology and cerebral vascular injury in the development of post-stroke cognitive impairment in the past. With the advent of novel radiotracers specific to cerebral amyloid plaques and tau protein, we aim to conduct a prospective multimodal neuroimaging cohort study to investigate the contribution of vascular injury, amyloid plaques and tau protein to stroke recovery and post-stroke cognitive impairment.

Enrollment: 200 estimated patients

Sex: All

Ages: 50 to 85 years old

Volunteers: Accepts Healthy Volunteers

Inclusion criteria

1. Inclusion criteria for acute stroke/TIA patients (Group A, n=200)

   • Males or females with age >= 50 years old
   • Having acute cerebral stroke or transient ischemic attack in recent 1 month
   • 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

2. Inclusion criteria for chronic stroke/TIA patients (Group B, n=200)

   • Males or females with age >= 50 years old
   • Having cerebral stroke or transient ischemic attack in the past 1.5 years
   • Having had tau PET imaging study within 1 year after the index stroke/TIA event
   • 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

3. Inclusion criteria for healthy elderly controls (Group C, n=30)

   • 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 at the initial screening 47.
• 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 3 months.
• 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]AV45 or [18F]THK5351.
• 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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200 participants in 2 patient groups

[18F]THK-5351

Other group

Description:

1. Primary endpoint A. To compare the distribution of cerebral amyloid plaques and tau protein between stroke patients and normal controls. 2. Secondary endpoints A. To compare tau distribution on \[18F\]THK5351 PET at acute, subacute and chronic stroke stages. B. To correlate the \[18F\]THK5351 PET findings with \[18F\]AV45 PET, brain MRI, and functional and cognitive performance. C. To compare the \[18F\]THK5351PET, \[18F\]AV45 PET, and brain MRI findings among stroke patients with no cognitive impairment (NCI), storke patients with VaMCI and stroke patients with PSD.

Treatment:

Drug: [18F]THK-5351

Drug: [18F]AV-45

[18F]AV-45

Other group

Description:

1. Primary endpoint A. To compare the distribution of cerebral amyloid plaques and tau protein between stroke patients and normal controls. 2. Secondary endpoints A. To compare tau distribution on \[18F\]THK5351 PET at acute, subacute and chronic stroke stages. B. To correlate the \[18F\]THK5351 PET findings with \[18F\]AV45 PET, brain MRI, and functional and cognitive performance. C. To compare the \[18F\]THK5351PET, \[18F\]AV45 PET, and brain MRI findings among stroke patients with no cognitive impairment (NCI), storke patients with VaMCI and stroke patients with PSD.

Treatment:

Drug: [18F]THK-5351

Drug: [18F]AV-45