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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

Tracking Information
First Submitted Date  ICMJE March 10, 2020
First Posted Date  ICMJE March 16, 2020
Last Update Posted Date March 16, 2020
Actual Study Start Date  ICMJE September 21, 2018
Estimated Primary Completion Date September 18, 2023   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: March 13, 2020)
  • 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.
  • Chi-square test will be performed to analyze dementia conversion rate. [ Time Frame: through study completion, an average of 1.5 year ]
Original Primary Outcome Measures  ICMJE Same as current
Change History No Changes Posted
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE The Influence of Vascular Burden, Amyloid Plaque and Tau Protein in Patients With Vascular Cognitive Impairment and Dementia With Tauopathy
Official Title  ICMJE The Influence of Vascular Burden, Amyloid Plaque and Tau Protein in Patients With Vascular Cognitive Impairment and Dementia With Tauopathy
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.

Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE 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
Condition  ICMJE Vascular Cognitive Impairment, Alzheimer's Disease, Fronto-temporal Dementia
Intervention  ICMJE
  • Drug: PMPBB3
    F-18 PMPBB3 PET Imaging
  • Drug: AV45
    F-18 AV45 PET Imaging
Study Arms  ICMJE
  • 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.

    Interventions:
    • Drug: PMPBB3
    • Drug: AV45
  • 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.

    Interventions:
    • Drug: PMPBB3
    • Drug: AV45
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: March 13, 2020)
220
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE September 18, 2024
Estimated Primary Completion Date September 18, 2023   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 20 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE Yes
Contacts  ICMJE
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
Listed Location Countries  ICMJE Taiwan
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04309253
Other Study ID Numbers  ICMJE 201800984A0
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Chang Gung Memorial Hospital
Study Sponsor  ICMJE Chang Gung Memorial Hospital
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Chair: Huang Kuo-Lun, M.D. Stroke Section, Department of Neurology, Chang-Gung memorial Hospital
PRS Account Chang Gung Memorial Hospital
Verification Date March 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP