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The Influence of [18F]PMPBB3 and [18F]THK5351 PET Distribution Patterns on Post-stroke Cognitive Impairment

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ClinicalTrials.gov Identifier: NCT04318626
Recruitment Status : Not yet recruiting
First Posted : March 24, 2020
Last Update Posted : July 22, 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 24, 2020
Last Update Posted Date July 22, 2020
Estimated Study Start Date  ICMJE October 1, 2020
Estimated Primary Completion Date January 15, 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: March 22, 2020)
  • CDR score of cognition deteriorating group and stable group [ Time Frame: through study completion, an average of 1 year ]
    The CDR is a 5-point scale (0、0.5、1、2、3) used to characterize six domains of cognitive and functional performance applicable to Alzheimer disease and related dementias: Memory, Orientation, Judgment & Problem Solving, Community Affairs, Home & Hobbies, and Personal Care. The necessary information to make each rating is obtained through a semi-structured interview of the patient and a reliable informant or collateral source (e.g., family member). Global score 0 = Normal、0.5 = Very Mild Dementia、1 = Mild Dementia、2 = Moderate Dementia、3 = Severe Dementia. The cognition deteriorating group is defined as CDR score declines from 0 or 0.5 at Month 3 to >=1 at Month 12. The cognition stable group is defined as CDR score remains at 0 or 0.5 at Month 12.
  • PET imaging positive and negative conditions [ Time Frame: through study completion, an average of 1 year ]
    PET images are visually assessed by independent raters, who are nuclear medicine doctors and blinded to all clinical and diagnostic information. The raters classify each scan as 0-1 (no significant uptake)、2 (suspicious uptake)、3-4 (significant uptake). The score >= 2 is deemed as positive condition.
  • Correlation between Neuroimaging factors and CDR-SB condition [ Time Frame: through study completion, an average of 1 year ]
    Neuroimaging continuous variables will be first examined for their collinearity, determined as variance inflation factor (VIF) of 2 or more. The approach suggested by Zuur et al is to calculate VIFs for each parameter in the model, and if they are larger than some cutoff, sequentially drop the predictor with the largest VIF, recalculate, and repeat until all values are below the cutoff of 2^68. Variables showing moderate to significant inter-group difference (P < 0.10) will be selected for the logistic regression analysis (CDR-SB increase > 1 and conversion to dementia as the dependent variables).
Original Primary Outcome Measures  ICMJE Same as current
Change History
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 [18F]PMPBB3 and [18F]THK5351 PET Distribution Patterns on Post-stroke Cognitive Impairment
Official Title  ICMJE The Influence of [18F]PMPBB3 and [18F]THK5351 PET Distribution Patterns on Post-stroke Cognitive Impairment
Brief Summary

Background and objects: Neuroinflammation is an active process detectable in the earliest stages of the neurodegeneration pathway. On the other hand, significant neuroinflammation, such as reactive astrocytosis, can also be observed after cerebral ischemic injury. [18F]THK5351 can monitor the neuroinflammatory process due to its high affinity to astrogliosis, and [18F]PMPBB3 is the novel tau protein radiotracer without significant off-target binding to MAO-B. The investigators hypothesize that the neuroinflammation after acute stroke may induce the tau protein accumulation. In the current proposal, our aims are to 1) explore the interaction between neuroinflammation and tau protein accumulation in acute stroke patients by applying both the [18F]PMPBB3 and [18F]THK5351 PET images and 2) determine their influence on the longterm stroke outcome and cognitive performance.

Method: The prospective project plans to recruit 2 groups of participants: one is patients with first-ever acute stroke (Group A, n=50), and the other is healthy people as the control group (Group B, n=30). Within 3 weeks of stroke, [18F]THK5351 and [18F]PMPBB3 PET will be done for imaging cerebral neuroinflammation and tau protein distribution. Brain MRI for obtaining structural and functional information will be done within 3 weeks and 3 months after stroke. Clinical and cognitive outcome will be evaluated at week 3 and months 3 and 12. 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]THK5351 and [18F]PMPBB3 PET, the study will be able to investigate the complex interaction between neuroinflammation and tau protein accumulation after stroke, and also evaluate their influence on structural changes, stroke outcome and cognitive performance. Group comparisons will be performed using the Chi-square test, independent t test, Mann-Whitney U test, and multiple linear regression, where appropriate.

Anticipation: In this project, the investigators will be able to identify the distribution patterns of neuroinflammation and tau protein accumulation after actue stroke. Secondly, the investigators expect that the presence of neuroinflammation and tau protein accumulation will interfere with the functional connectivity. Finally, the investigators expect that the extent of neuroinflammation and tau protein is correlated with stroke outcome and post-stroke cognitive impairment.

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 acute stroke/TIA, n=50. B. Group B: Normal control, n=30.
Masking: Single (Investigator)
Primary Purpose: Diagnostic
Condition  ICMJE
  • Post-stroke Cognitive Impairment
  • Neuroinflammation
Intervention  ICMJE
  • Drug: PMPBB3
    F-18 PMPBB3 PET Imaging
  • Drug: THK5351
    F-18 THK5351 PET Imaging
Study Arms  ICMJE
  • PMPBB3
    1. Name: [18F] PMPBB3,[18F]1-Fluoro-3-((2-((1E,3E)-4-(6-(methylamino)pyridin-3-yl)buta-1,3-dien-1-yl)ben
    2. Dosage form: intravenous injection
    3. Dose(s): 7mCi
    4. Dosing schedule: Visit 2
    5. Mechanism of action (if known): high affinity radiotracer for the tau protein
    6. Pharmacological category:Radio pharmaceutical
    Interventions:
    • Drug: PMPBB3
    • Drug: THK5351
  • THK
    1. Name: [18F]THK5351,(S)-6-[(3-Fluoro-2-hydroxy)propoxy]-2-(2-Methylaminopyrid-5-yl)-quinoline
    2. Dosage form: intravenous injection
    3. Dose(s): 10mCi
    4. Dosing schedule: Visit 2
    5. Mechanism of action (if known): high affinity radiotracer for the tau protein
    6. Pharmacological category:Radio pharmaceutical
    Interventions:
    • Drug: PMPBB3
    • Drug: THK5351
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 Not yet recruiting
Estimated Enrollment  ICMJE
 (submitted: March 22, 2020)
80
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE January 15, 2022
Estimated Primary Completion Date January 15, 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  1. Inclusion criteria for acute stroke/TIA patients (Group A, n=50)

    • Males or females with age >= 20 years old.
    • Having acute cerebral stroke or transient ischemic attack in recent 1 month.
    • Female subjects of childbearing potential must practice effective contraception during the - Provision of signed informed consent from the subject and the subject's legally
    • The subject has an appropriate caregiver capable of accompanying the subject, if necessary.
  2. Inclusion criteria for healthy controls (Group B, n = 30)

    • Males or females with age >= 20 years old
    • Without history of cerebral stroke or transient ischemic attack
    • Without history of mild cognitive impairment or dementia
    • Ability to participate in cognitive and neuroimaging assessments
    • Female subjects of childbearing potential must practice effective contraception during the study and be willing and able to continue contraception after the final study
    • Provision of signed informed consent

Exclusion Criteria:

  1. Exclusion criteria for acute stroke/TIA patients (Group A, n = 50)

    • Presence of dementia diagnosis before the index stroke or at the initial screening
    • History of vascular MCI (VaMCI)
    • The Chinese version of the Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE) score >=104 at the initial screening 45.
    • Life expectancy less than 1 year.
    • Clinically significant abnormal laboratory values.
    • 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.
    • General MRI, and / or PET exclusion criteria.
    • Pregnant or becoming pregnant during the study (as documented by pregnancy testing at screening or at any date during the study according to the PI discretion) or current breast feeding.
    • History of allergy to 18F-labelled radionucleic agents, such as [18F]PMPBB3 or [18F]THK5351.
    • Subjects having high risks for the study according to the PI discretion.
  2. Exclusion criteria for healthy controls (Group B, n = 30)

    • The Chinese version of the Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE) score >=104 at the initial screening 45.
    • Life expectancy less than 1 year.
    • Clinically significant abnormal laboratory values.
    • 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.
    • General MRI, and / or PET exclusion criteria.
    • Pregnant or becoming pregnant during the study (as documented by pregnancy testing at screening or at any date during the study according to the PI discretion) or current breast feeding.
    • History of allergy to 18F-labelled radionucleic agents, such as [18F]PMPBB3 or [18F]THK5351.
    • Subjects having high risks for the study according to the PI discretion.
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 NCT04318626
Other Study ID Numbers  ICMJE 201802299A0
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 Not Provided
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