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

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ClinicalTrials.gov Identifier: NCT04309253
Recruitment Status : Recruiting
First Posted : March 16, 2020
Last Update Posted : March 16, 2020
Sponsor:
Information provided by (Responsible Party):
Chang Gung Memorial Hospital

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=200), Alzheimer's disease/mild cognitive impairment (MCI) (Group B, n = 200), and fronto-temporal dementia (FTD) (Group C, n =30). In addition, another 60 healthy people will be recruited as the control group (Group D, n=60). [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 and carotid ultrasound 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 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.


Condition or disease Intervention/treatment Phase
Vascular Cognitive Impairment, Alzheimer's Disease, Fronto-temporal Dementia Drug: PMPBB3 Drug: AV45 Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 220 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: 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.
Masking: Single (Investigator)
Primary Purpose: Diagnostic
Official Title: The Influence of Vascular Burden, Amyloid Plaque and Tau Protein in Patients With Vascular Cognitive Impairment and Dementia With Tauopathy
Actual Study Start Date : September 21, 2018
Estimated Primary Completion Date : September 18, 2023
Estimated Study Completion Date : September 18, 2024


Arm Intervention/treatment
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

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




Primary Outcome Measures :
  1. 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.

  2. Chi-square test will be performed to analyze dementia conversion rate. [ Time Frame: through study completion, an average of 1.5 year ]


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Ages Eligible for Study:   20 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
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=80)

    • 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.

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04309253


Contacts
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Contact: Huang Kuo-Lun, M.D. +886-3-3281200 ext 8340 drkuolun@cgmh.org.tw
Contact: Tseng Yu-Hui +886-3-3281200 ext 7901 julie031422@gmail.com

Locations
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Taiwan
Department of Neurology, Chang-Gung memorial Hospital Recruiting
Taoyuan, Guishan, Taiwan, 333
Contact: Huang Kuo-Lun, M.D.    +886-3-3281200 ext 8340    drkuolun@cgmh.org.tw   
Contact: Tseng Yu-Hui    +886-3-3281200 ext 7901    julie031422@gmail.com   
Sponsors and Collaborators
Chang Gung Memorial Hospital
Investigators
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Study Chair: Huang Kuo-Lun, M.D. Stroke Section, Department of Neurology, Chang-Gung memorial Hospital
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Responsible Party: Chang Gung Memorial Hospital
ClinicalTrials.gov Identifier: NCT04309253    
Other Study ID Numbers: 201800984A0
First Posted: March 16, 2020    Key Record Dates
Last Update Posted: March 16, 2020
Last Verified: March 2020

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Chang Gung Memorial Hospital:
Vascular cognitive impairment, Alzheimer's disease, fronto-temporal dementia, amyloid plaque, tau protein
Additional relevant MeSH terms:
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Alzheimer Disease
Dementia
Tauopathies
Frontotemporal Dementia
Aphasia, Primary Progressive
Pick Disease of the Brain
Plaque, Amyloid
Cognitive Dysfunction
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Neurodegenerative Diseases
Neurocognitive Disorders
Mental Disorders
Cognition Disorders
Proteostasis Deficiencies
Metabolic Diseases
Pathological Conditions, Anatomical
Frontotemporal Lobar Degeneration
TDP-43 Proteinopathies
Aphasia
Speech Disorders
Language Disorders
Communication Disorders
Neurobehavioral Manifestations
Neurologic Manifestations
Signs and Symptoms