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

April 28, 2023 updated by: Chang Gung Memorial Hospital

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

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Anticipated)

220

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • Taiwan
    • Guishan
      • Taoyuan, Guishan, Taiwan, 333
        • Recruiting
        • Department of Neurology, Chang-Gung memorial Hospital
        • Contact:
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

16 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

Yes

Description

Inclusion Criteria:

  1. Inclusion criteria for VCI (Group A, n=80)

    • 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.

  2. Inclusion criteria for AD / MCI (Group B, n=120)

    • 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.

  3. Inclusion criteria for FTD (Group C, n=30)

    • 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.

  4. Inclusion criteria for normal control (Group D, n=30)

    • Males or females with age >= 20 years old.
    • Provision of signed informed consent.

  5. Inclusion criteria for PSP (Group E, n=80)

    • Males or females with age >= 20 years old
    • Patients fulfill the 2017 Movement Disorder Society criteria of PSP.
    • 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.

Exclusion Criteria:

  • 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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Diagnostic
  • Allocation: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Single

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Other: PMPBB3

  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
F-18 PMPBB3 PET Imaging
Drug: AV45
F-18 AV45 PET Imaging
Other: AV45

  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
F-18 PMPBB3 PET Imaging
Drug: AV45
F-18 AV45 PET Imaging

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Chi-square test will be performed to analyze dementia conversion rate.
Time Frame: through study completion, an average of 1.5 year
through study completion, an average of 1.5 year
The Clinical Dementia Rating-Sum of Boxes (CDR-SB) change score
Time Frame: through study completion, an average of 1.5 year
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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Chang Gung Memorial Hospital

Investigators

  • Study Chair: Huang Kuo-Lun, M.D., Stroke Section, Department of Neurology, Chang-Gung memorial Hospital

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

September 21, 2018

Primary Completion (Anticipated)

May 18, 2024

Study Completion (Anticipated)

November 30, 2025

Study Registration Dates

First Submitted

March 10, 2020

First Submitted That Met QC Criteria

March 13, 2020

First Posted (Actual)

March 16, 2020

Study Record Updates

Last Update Posted (Actual)

May 1, 2023

Last Update Submitted That Met QC Criteria

April 28, 2023

Last Verified

April 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 201800984A0

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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