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RecruitingNCT04309253Updated May 1, 2023

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

A Phase 2 interventional study of PMPBB3 and AV45 in Vascular Cognitive Impairment, Alzheimer's Disease, Fronto-temporal Dementia, sponsored by Chang Gung Memorial Hospital. Recruiting at 1 site in Taiwan. Open to participants aged 20 Years and older, including healthy volunteers. Per ClinicalTrials.gov, last updated 2023-05-01.

Sponsored by Chang Gung Memorial Hospital · Phase 2, Interventional, and Diagnostic

Phase
Phase 2
Study type
Interventional
Enrollment
220
Allocation
Non-randomized
Ages
20 Years and older
Sex
All
01

Study 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

02

Conditions studied

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

Keywords

  • Vascular cognitive impairment, Alzheimer's disease, fronto-temporal dementia, amyloid plaque, tau protein
03

Who can participate

Ages eligible
20 Years and older
Sexes eligible
All
Accepts healthy volunteers
Yes

Eligibility criteria

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.
04

Study design

Phase
Phase 2
Primary purpose
Diagnostic
Allocation
Non-randomized
Intervention model
Parallel assignment
Masking
Single (Investigator)
Enrollment
220 participants (estimated)

Study arms

  • 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 · Drug: AV45

  • 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 · Drug: AV45

Interventions

  • DrugPMPBB3

    F-18 PMPBB3 PET Imaging

  • DrugAV45

    F-18 AV45 PET Imaging

05

What researchers measure

Primary outcomes

  1. 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.

    Time frame: through study completion, an average of 1.5 year

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

    Time frame: through study completion, an average of 1.5 year

06

Study locations

1 of 1 sites recruiting
  • Department of Neurology, Chang-Gung memorial Hospital
    Taoyuan, Guishan 333, Taiwan
    Recruiting
07

Registry details

Key details

Study ID
NCT04309253
Lead sponsor
Chang Gung Memorial Hospital
Responsible party
Sponsor
First posted
Mar 16, 2020
Start date
Sep 21, 2018
Primary completion
May 18, 2024 (estimated)
Completion
Nov 30, 2025 (estimated)
Last update
May 1, 2023

Study contacts

Huang Kuo-Lun, M.D.
Contact
drkuolun@cgmh.org.tw
+886-3-3281200 ext. 8340
Chen Jing-Fang
Contact
tp6tp6fg@gmail.com
+886-3-3281200 ext. 8413
Huang Kuo-Lun, M.D.
study chair · Stroke Section, Department of Neurology, Chang-Gung memorial Hospital

Oversight

FDA-regulated drug
No
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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