The Influence of [18F]PMPBB3 and [18F]THK5351 PET Distribution Patterns on Post-stroke Cognitive Impairment
|ClinicalTrials.gov Identifier: NCT04318626|
Recruitment Status : Not yet recruiting
First Posted : March 24, 2020
Last Update Posted : March 24, 2020
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.
|Condition or disease||Intervention/treatment||Phase|
|Post-stroke Cognitive Impairment Neuroinflammation||Drug: PMPBB3 Drug: THK5351||Phase 2|
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||80 participants|
|Intervention Model:||Parallel Assignment|
|Intervention Model Description:||A. Group A: Patients with acute stroke/TIA, n=50. B. Group B: Normal control, n=30.|
|Official Title:||The Influence of [18F]PMPBB3 and [18F]THK5351 PET Distribution Patterns on Post-stroke Cognitive Impairment|
|Estimated Study Start Date :||May 1, 2020|
|Estimated Primary Completion Date :||January 15, 2021|
|Estimated Study Completion Date :||January 15, 2022|
F-18 PMPBB3 PET Imaging
F-18 THK5351 PET Imaging
F-18 PMPBB3 PET Imaging
F-18 THK5351 PET Imaging
- 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).
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04318626
|Contact: Huang Kuo-Lun, M.D.||+886-3-3281200 ext firstname.lastname@example.org|
|Contact: Tseng Yu-Hui||+886-3-3281200 ext email@example.com|