The Influence of Vascular Burden, Amyloid Plaque and Tau Protein in Patients With Vascular Cognitive Impairment and Dementia With Tauopathy

NCT04309253 | Unknown Phase 2

• 1 other identifier: 201800984A0
• Study Type: interventional
• Target: 220
• Locations: 1 country
• Sites: 1

Brief Summary

Background and objects 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 during the post-stroke cognitive impairment development 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 plaque and tau protein to cognitive impairment. Subjects and methods The prospective project plans to recruit patients with vascular cognitive impairment (VCI) (Group A, n=80), Alzheimer's disease/mild cognitive impairment (MCI) (Group B, n = 120), fronto-temporal dementia (FTD) (Group C, n =30), and progressive supranuclear palsy (PSP) (Group E, n = 80). In addition, another 30 healthy people will be recruited as the control group (Group D, n=30). \[18F\]AV45 and \[18F\]MNI-958(PMPBB3) PET will be done for imaging cerebral amyloid plaque and tau protein distribution, brain MRI for obtaining structural and functional information, and neuropsychological tests for cognitive performance. Cognitive evaluation will be repeated 18 months after recruitment. In addition, APOE genotyping will be performed as well. By obtaining the neuroimaging information, such as severity of white matter change and infarction, cortical and hippocampal atrophy, and SUVRs of \[18F\]AV-45 and \[18F\]MNI-958(PMPBB3) PET, the study will be able to investigate the composite influence of cerebrovascular disease and neurodegenerative pathology on the trajectory of cognitive impairment. Group comparisons will be performed using the Chi-square test, independent t test, Mann-Whitney U test, ANOVA test, and multiple linear regression, where appropriate. Anticipation In this project, we will be able to explore the distribution patterns of amyloid plaque and tau protein among dementia patients with different etiologies, and also evaluate their influence on cognition

Conditions

Vascular Cognitive Impairment, Alzheimer's Disease, Fronto-temporal Dementia

Keywords

Vascular cognitive impairment, Alzheimer's disease, fronto-temporal dementia, amyloid plaque, tau protein

Outcome Measures

Primary Outcomes (2)

• The Clinical Dementia Rating-Sum of Boxes (CDR-SB) change score

  The Clinical Dementia Rating-Sum of Boxes (CDR-SB) change score between baseline and 18-month follow-up will be calculated for primary endpoint determination. Two-sample independent t-test will be performed to compare the CDR-SB change score between patients positive and negative for tau protein accumulation. Patients will be stratified into tau-positive and tau-negative groups, and the presentations of their cognitive state will be recorded at the 18-month follow-up visit.

  through study completion, an average of 1.5 year

• Chi-square test will be performed to analyze dementia conversion rate.

  through study completion, an average of 1.5 year

Study Arms (2)

PMPBB3

OTHER

1. Primary endpoint(s): A. To determine the distribution patterns of cerebral amyloid plaques and Tau protein among AD/MCI, VCI and FTP patients as well as normal controls. 2. Secondary endpoints: A. To correlate vascular burden, \[18F\]AV45 and \[18F\]MNI-958(PMPBB3) retention with clinical presentation and cognitive performance among different groups of subjects B. To determine the impacts of vascular burden, \[18F\]AV45 and \[18F\]MNI-958(PMPBB3) retention changes on cognitive trajectory over the 18-month follow-up period.

Drug: PMPBB3; Drug: AV45

AV45

OTHER

1. Primary endpoint(s): A. To determine the distribution patterns of cerebral amyloid plaques and Tau protein among AD/MCI, VCI and FTP patients as well as normal controls. 2. Secondary endpoints: A. To correlate vascular burden, \[18F\]AV45 and \[18F\]MNI-958(PMPBB3) retention with clinical presentation and cognitive performance among different groups of subjects B. To determine the impacts of vascular burden, \[18F\]AV45 and \[18F\]MNI-958(PMPBB3) retention changes on cognitive trajectory over the 18-month follow-up period.

Drug: PMPBB3; Drug: AV45

Interventions

PMPBB3 DRUG

F-18 PMPBB3 PET Imaging

AV45; PMPBB3

AV45 DRUG

F-18 AV45 PET Imaging

AV45; PMPBB3

Eligibility Criteria

• Age: 20 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Males or females with age \>= 20 years old.
• Patients fulfill the AHA/ASA criteria for vascular cognitive impairment.
• Provision of signed informed consent from the subject and the subject's legally authorized representative or caregiver (if applicable).
• The subject has an appropriate caregiver capable of accompanying the subject, if necessary.
• Males or females with age \>= 20 years old.
• Patients fulfill the National Institute on Aging (NIA) - Alzheimer's Association Diagnostic Guidelines.
• Provision of signed informed consent from the subject and the subject's legally authorized representative or caregiver (if applicable).
• The subject has an appropriate caregiver capable of accompanying the subject, if necessary.
• Males or females with age \>= 20 years old.
• Patients fulfill the criteria of probable FTD.
• Provision of signed informed consent from the subject and the subject's legally authorized representative or caregiver (if applicable).
• The subject has an appropriate caregiver capable of accompanying the subject, if necessary.
• Males or females with age \>= 20 years old.
• Provision of signed informed consent.
• Males or females with age \>= 20 years old

You may not qualify if:

• Life expectancy less than 1 year.
• Clinically significant abnormal laboratory values (such as AST/ALT \>= 3X of upper normal limits).
• 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.
• Stroke history within the recent 3 months.

Sponsors & Collaborators

• Chang Gung Memorial Hospital: lead

Study Sites (1)

Department of Neurology, Chang-Gung memorial Hospital

Taoyuan District, Guishan, 333, Taiwan

RECRUITING

MeSH Terms

Conditions

Alzheimer Disease; Plaque, Amyloid; Frontotemporal Dementia

Condition Hierarchy (Ancestors)

Dementia; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Tauopathies; Neurodegenerative Diseases; Neurocognitive Disorders; Mental Disorders; Pathological Conditions, Anatomical; Pathological Conditions, Signs and Symptoms; Frontotemporal Lobar Degeneration; TDP-43 Proteinopathies; Proteostasis Deficiencies; Metabolic Diseases; Nutritional and Metabolic Diseases

Study Officials

• Huang Kuo-Lun, M.D.

  Stroke Section, Department of Neurology, Chang-Gung memorial Hospital

  STUDY CHAIR

Central Study Contacts

Huang Kuo-Lun, M.D.

CONTACT

+886-3-3281200; drkuolun@cgmh.org.tw

Chen Jing-Fang

CONTACT

+886-3-3281200; tp6tp6fg@gmail.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: SINGLE
• Who Masked: INVESTIGATOR
• Purpose: DIAGNOSTIC
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: A. Group A: Patients with vascular cognitive impairment (VCI), n=80. B. Group B: Alzheimer's disease/mild cognitive impairment (MCI), n=80. C. Group C: Fronto-temporal dementia (FTD), n=30. D. Group D: Normal control, n=30. E. Group E: progressive supranuclear palsy(PSP), n=80.

Study Record Dates

• First Submitted: March 10, 2020
• First Posted: March 16, 2020
• Study Start: September 21, 2018
• Primary Completion: May 18, 2024
• Study Completion: November 30, 2025
• Last Updated: May 1, 2023

Record last verified: 2023-04

Locations

TW (1)