The Aging Brain and Cognition: Contribution of Vascular Injury, Amyloid Plaque and Tau Protein to Cognitive Dysfunction After Stroke

NCT04588649 | Completed Phase 2

• 1 other identifier: 103-7584A
• Study Type: interventional
• Target: 181
• Locations: 1 country
• Sites: 1

Brief Summary

Stroke can lead to signficiant neurological deficits, and about one-third of stroke patients will be diagnosed of vascular mild cognitive impairment or post-stroke dementia. Post-stroke dementia includes all types of dementia that happen after stroke, irrespective of their cause, and vascular dementia (VaD), degenerative dementia (especially Alzheimer's disease), or mixed dementia (dementia as a result of the coexistence of vascular lesions of the brain and neurodegenerative lesions) are the most common causes of post-stroke dementia. However, it is difficult to determine to what extent cognitive impairment may be attributable to stroke versus concomitant Alzheimer disease. With the advent of PET imaging technique, we are able to conduct a multi-modal neuroimaging study to explore the composite influence of vascular injury, amyloid plaque and Tau protein the the cognitive performance after stroke.

Conditions

Post-stroke Dementia; Vascular Mild Cognitive Impairment

Outcome Measures

Primary Outcomes (2)

• CDR score of cognition deteriorating group and stable group

  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 18. The cognition stable group is defined as CDR score remains at 0 or 0.5 at Month 18.

  through study completion, an average of 1.5 year

• Imaging positive and negative conditions

  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.

  through study completion, an average of 1.5 year

Study Arms (2)

THK-5351

OTHER

Name: \[18F\]THK5351，(S)-6-\[(3-Fluoro-2-hydroxy)propoxy\]-2-(2-Methylaminopyrid-5-yl)-quinoline Dosage form: intravenous injection Dose(s): 10mCi Dosing schedule: Visit 2 Mechanism of action (if known): high affinity radiotracer for the tau protein Pharmacological category：Radio pharmaceutical

Drug: THK-5351; Drug: AV-45

AV-45

OTHER

Name: \[18F\]AV-45, (E)-4-(2-(6-(2-(2-(2-\[18F\]fluoroethoxy) ethoxy) ethoxy)pyridin-3-yl)vinyl)-N-methylbenzenamine Dosage form: intravenous injection Dose(s): 10mCi Dosing schedule: Visit 2 Mechanism of action (if known): high affinity radiotracer for the β- amyloid protein Pharmacological category：Radio pharmaceutical

Drug: THK-5351; Drug: AV-45

Interventions

THK-5351 DRUG

\[18F\]THK-5351 PET Imaging

AV-45; THK-5351

AV-45 DRUG

\[18F\]AV-45 PET Imaging

AV-45; THK-5351

Eligibility Criteria

• Age: 50 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Males or females with age \>= 50 years old
• Having cerebral stroke or transient ischemic attack
• Modified Rankin Scale \< 4
• 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
• Males or females with age \>= 50 years old
• Without history of cerebral stroke or transient ischemic attack
• 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

You may not qualify if:

• 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 \[24\] at the initial screening.
• Presence of large infarction or lobar encephalomalacia on brain CT or MRI.
• Severe language impairment precluding cognitive assessments, defined as a score of 3 points in the language score of the National Institute of Health Stroke Scale.
• 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 1 year
• 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, \[18F\]AV-45 or \[18F\]THK-5351.
• Subjects having high risks for the study according to the PI discretion.

Sponsors & Collaborators

• Chang Gung Memorial Hospital: lead

Study Sites (1)

Department of Neurology, Chang-Gung memorial Hospital

Taoyuan District, Guishan, 333, Taiwan

Location

MeSH Terms

Interventions

THK5351

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: SINGLE
• Who Masked: INVESTIGATOR
• Purpose: DIAGNOSTIC
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: * GroupA (Stroke/TIA patients), n=300 * Group (healthy elderly controls), n=30

Study Record Dates

• First Submitted: September 29, 2020
• First Posted: October 19, 2020
• Study Start: January 4, 2016
• Primary Completion: March 29, 2016
• Study Completion: December 31, 2019
• Last Updated: May 6, 2023

Record last verified: 2020-09

Locations

TW (1)