Post-stroke Cognitive ImpairmentPhase 2NCT04318626
The Influence of [18F]PMPBB3 and [18F]THK5351 PET Distribution Patterns on Post-stroke Cognitive Impairment
A Phase 2 study testing PMPBB3 and THK5351 in people with Post-stroke Cognitive Impairment and Neuroinflammation, run by Chang Gung Memorial Hospital at 1 site in Taiwan.
Trial 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. Read more about this study
- Who is it for?
- Ages 20 years and olderHealthy volunteers can take part
- Conditions the study is for
- Post-stroke Cognitive Impairment, Neuroinflammation
- What is being tested?
- PMPBB3 and THK5351
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 80 participants
- Where
- 1 siteTaiwan
- Study dates
- 1 Nov 2020to 31 Jul 2024
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 20 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- 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.
- Inclusion criteria for healthy controls (Group B, n = 30)
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- 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
Who cannot join
- 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.
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- 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.
- 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.
Trial locations and contacts
1 site in 1 country.
Taiwan1 site, 1 recruiting
- Recruiting
Department of Neurology, Chang-Gung memorial Hospital
Taoyuan, Guishan, 333
Huang Kuo-Lun, M.D., +886-3-3281200 ext. 8340, drkuolun@cgmh.org.tw
Chen Jing-Fang, +886-3-3281200 ext. 8413, tp6tp6fg@gmail.com
About this study
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.
- Being tested
- PMPBB3, THK5351
- Keywords
- Post-stroke cognitive impairment, PET, MRI, neuroinflammation, tau protein
- Medical subject headings
- Neuroinflammatory Diseases, Frontotemporal Dementia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PMPBB3Drug
F-18 PMPBB3 PET Imaging
THK5351Drug
F-18 THK5351 PET Imaging
| Study group | Role | What they receive |
|---|---|---|
| PMPBB3 | Other | 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 Receives: Drug: PMPBB3; Drug: THK5351 |
| THK | Other | 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 Receives: Drug: PMPBB3; Drug: THK5351 |
What is being measured
The primary outcome is the main question the study is designed to answer.
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 12. The cognition stable group is defined as CDR score remains at 0 or 0.5 at Month 12.
Measured: through study completion, an average of 1 year
PET 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.
Measured: through study completion, an average of 1 year
Correlation between Neuroimaging factors and CDR-SB condition
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).
Measured: through study completion, an average of 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Mar 2020
- Study start1 Nov 2020
- Primary completion31 Jul 2023 (estimated)
- Study completion31 Jul 2024 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Post-stroke Cognitive ImpairmentStudies of the same condition, open and under way.
- More trials run by Chang Gung Memorial HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Diagnosis
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Model description
- A. Group A: Patients with acute stroke/TIA, n=50. B. Group B: Normal control, n=30.
- Masking
- Single blind
- Who is masked
- Investigator
- Enrolment
- 80 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Chang Gung Memorial Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04318626
- Sponsor's protocol ID
- 201802299A0
- Status last verified
- Apr 2023
- First submitted
- 10 Mar 2020
- Last updated
- 1 May 2023
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 1 May 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Influence of [18F]PMPBB3 and [18F]THK5351 PET Distribution Patterns on Post-stroke Cognitive Impairment
- ClinicalTrials.gov ID
- NCT04318626
- Acronym / sponsor ID
- 201802299A0
- Keywords
- Post-stroke cognitive impairment, PET, MRI, neuroinflammation, tau protein
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 80 participants (estimated)
- Lead sponsor
- Chang Gung Memorial HospitalUniversity, hospital or other
- Study start
- 1 Nov 2020 (actual)
- Primary completion
- 31 Jul 2023 (estimated)
- Study completion
- 31 Jul 2024 (estimated)
- First posted
- 24 Mar 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Diagnosis
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (investigator)
- Number of arms
- 2
- Model description
- A. Group A: Patients with acute stroke/TIA, n=50. B. Group B: Normal control, n=30.
| Arm | Type | Receives |
|---|---|---|
| PMPBB3 | Other | Drug: PMPBB3, Drug: THK53511. 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 |
| THK | Other | Drug: PMPBB3, Drug: THK53511. 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 |
Who may qualify
- Ages
- 20 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- Inclusion criteria for acute stroke/TIA patients (Group A, n=50)
- Inclusion criteria for healthy controls (Group B, n = 30)
Key exclusion criteria (26 listed)
- Exclusion criteria for acute stroke/TIA patients (Group A, n = 50)
- Exclusion criteria for healthy controls (Group B, n = 30)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| PMPBB3F-18 PMPBB3 PET Imaging | Drug | PMPBB3, THK |
| THK5351F-18 THK5351 PET Imaging | Drug | PMPBB3, THK |
Primary outcome
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).
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 May 2023.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing PMPBB3 and THK5351 in people with Post-stroke Cognitive Impairment and Neuroinflammation, run by Chang Gung Memorial Hospital at 1 site in Taiwan.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 12 inclusion and 26 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 1 May 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Taiwan. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Huang Kuo-Lun, M.D. (+886-3-3281200 ext. 8340, drkuolun@cgmh.org.tw), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
CDR score of cognition deteriorating group and stable group (time frame: through study completion, an average of 1 year). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 May 2023.