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

Primary Purpose

Post-stroke Dementia, Vascular Mild Cognitive Impairment

Status
Completed
Phase
Phase 2
Locations
Taiwan
Study Type
Interventional
Intervention
THK-5351
AV-45
Sponsored by
Chang Gung Memorial Hospital
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional diagnostic trial for Post-stroke Dementia

Eligibility Criteria

50 Years - undefined (Adult, Older Adult)All SexesAccepts Healthy Volunteers

Inclusion Criteria:

Inclusion criteria for stroke/TIA patients

  • 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

Inclusion criteria for healthy elderly controls

  • 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

Exclusion Criteria:

Exclusion criteria for all subjects

  • 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
  • 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, [18F]AV-45 or [18F]THK-5351.
  • Subjects having high risks for the study according to the PI discretion.

Sites / Locations

  • Department of Neurology, Chang-Gung memorial Hospital

Arms of the Study

Arm 1

Arm 2

Arm Type

Other

Other

Arm Label

THK-5351

AV-45

Arm Description

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

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

Outcomes

Primary Outcome Measures

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.
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.

Secondary Outcome Measures

Full Information

First Posted
September 29, 2020
Last Updated
May 2, 2023
Sponsor
Chang Gung Memorial Hospital
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1. Study Identification

Unique Protocol Identification Number
NCT04588649
Brief Title
The Aging Brain and Cognition: Contribution of Vascular Injury, Amyloid Plaque and Tau Protein to Cognitive Dysfunction After Stroke
Official Title
The Aging Brain and Cognition: Contribution of Vascular Injury, Amyloid Plaque and Tau Protein to Cognitive Dysfunction After Stroke
Study Type
Interventional

2. Study Status

Record Verification Date
September 2020
Overall Recruitment Status
Completed
Study Start Date
January 4, 2016 (Actual)
Primary Completion Date
March 29, 2016 (Actual)
Study Completion Date
December 31, 2019 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Chang Gung Memorial Hospital

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Post-stroke Dementia, Vascular Mild Cognitive Impairment

7. Study Design

Primary Purpose
Diagnostic
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Model Description
GroupA (Stroke/TIA patients), n=300 Group (healthy elderly controls), n=30
Masking
Investigator
Allocation
Non-Randomized
Enrollment
181 (Actual)

8. Arms, Groups, and Interventions

Arm Title
THK-5351
Arm Type
Other
Arm Description
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
Arm Title
AV-45
Arm Type
Other
Arm Description
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
Intervention Type
Drug
Intervention Name(s)
THK-5351
Intervention Description
[18F]THK-5351 PET Imaging
Intervention Type
Drug
Intervention Name(s)
AV-45
Intervention Description
[18F]AV-45 PET Imaging
Primary Outcome Measure Information:
Title
CDR score of cognition deteriorating group and stable group
Description
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.
Time Frame
through study completion, an average of 1.5 year
Title
Imaging positive and negative conditions
Description
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.
Time Frame
through study completion, an average of 1.5 year

10. Eligibility

Sex
All
Minimum Age & Unit of Time
50 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria: Inclusion criteria for stroke/TIA patients 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 Inclusion criteria for healthy elderly controls 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 Exclusion Criteria: Exclusion criteria for all subjects 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 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, [18F]AV-45 or [18F]THK-5351. Subjects having high risks for the study according to the PI discretion.
Facility Information:
Facility Name
Department of Neurology, Chang-Gung memorial Hospital
City
Taoyuan
State/Province
Guishan
ZIP/Postal Code
333
Country
Taiwan

12. IPD Sharing Statement

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

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