Vascular Cognitive Impairment, Alzheimer's Disease, Fronto-temporal DementiaPhase 2NCT04309253
The Influence of Vascular Burden, Amyloid Plaque and Tau Protein in Patients With Vascular Cognitive Impairment and Dementia With Tauopathy
A Phase 2 study testing PMPBB3 and AV45 in people with Vascular Cognitive Impairment, Alzheimer's Disease, Fronto-temporal Dementia, run by Chang Gung Memorial Hospital at 1 site in Taiwan.
Trial summary
Background and objects Amyloid plaques and tau protein are the landmarks of neurodegeneration in Alzheimer's disease (AD). On the other hand, it is reported that cerebral ischemia may induce amyloid plaques and tau protein accumulation. Read more about this study
- Who is it for?
- Ages 20 years and olderHealthy volunteers can take part
- Conditions the study is for
- Vascular Cognitive Impairment, Alzheimer's Disease, Fronto-temporal Dementia
- What is being tested?
- PMPBB3 and AV45
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 220 participants
- Where
- 1 siteTaiwan
- Study dates
- 21 Sep 2018to 30 Nov 2025
- 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 VCI (Group A, n=80)
- Males or females with age >= 20 years old.
- Patients fulfill the AHA/ASA criteria for vascular cognitive impairment.
- Provision of signed informed consent from the subject and the subject's legally authorized representative or caregiver (if applicable).
- The subject has an appropriate caregiver capable of accompanying the subject, if necessary.
- Inclusion criteria for AD / MCI (Group B, n=120)
Show all 23Show fewer
- Males or females with age >= 20 years old.
- Patients fulfill the National Institute on Aging (NIA) - Alzheimer's Association Diagnostic Guidelines.
- Provision of signed informed consent from the subject and the subject's legally authorized representative or caregiver (if applicable).
- The subject has an appropriate caregiver capable of accompanying the subject, if necessary.
- Inclusion criteria for FTD (Group C, n=30)
- Males or females with age >= 20 years old.
- Patients fulfill the criteria of probable FTD.
- Provision of signed informed consent from the subject and the subject's legally authorized representative or caregiver (if applicable).
- The subject has an appropriate caregiver capable of accompanying the subject, if necessary.
- Inclusion criteria for normal control (Group D, n=30)
- Males or females with age >= 20 years old.
- Provision of signed informed consent.
- Inclusion criteria for PSP (Group E, n=80)
- Males or females with age >= 20 years old
- Patients fulfill the 2017 Movement Disorder Society criteria of PSP.
- Provision of signed informed consent from the subject and the subject's legally authorized representative or caregiver (if applicable)
- The subject has an appropriate caregiver capable of accompanying the subject, if necessary.
Who cannot join
- Life expectancy less than 1 year.
- Clinically significant abnormal laboratory values (such as AST/ALT >= 3X of upper normal limits).
- 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.
- Stroke history within the recent 3 months.
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 Amyloid plaques and tau protein are the landmarks of neurodegeneration in Alzheimer's disease (AD). On the other hand, it is reported that cerebral ischemia may induce amyloid plaques and tau protein accumulation. However, it was difficult to in vivo disentangle the complex and dynamic interactions between AD pathophysiology and cerebral vascular injury during the post-stroke cognitive impairment development in the past. With the advent of novel radiotracers specific to cerebral amyloid plaques and tau protein, we aim to conduct a prospective multimodal neuroimaging cohort study to investigate the contribution of vascular injury, amyloid plaque and tau protein to cognitive impairment.
Subjects and methods The prospective project plans to recruit patients with vascular cognitive impairment (VCI) (Group A, n=80), Alzheimer's disease/mild cognitive impairment (MCI) (Group B, n = 120), fronto-temporal dementia (FTD) (Group C, n =30), and progressive supranuclear palsy (PSP) (Group E, n = 80). In addition, another 30 healthy people will be recruited as the control group (Group D, n=30). [18F]AV45 and [18F]MNI-958(PMPBB3) PET will be done for imaging cerebral amyloid plaque and tau protein distribution, brain MRI for obtaining structural and functional information, and neuropsychological tests for cognitive performance. Cognitive evaluation will be repeated 18 months after recruitment. In addition, APOE genotyping will be performed as well.
Read more
By obtaining the neuroimaging information, such as severity of white matter change and infarction, cortical and hippocampal atrophy, and SUVRs of [18F]AV-45 and [18F]MNI-958(PMPBB3) PET, the study will be able to investigate the composite influence of cerebrovascular disease and neurodegenerative pathology on the trajectory of cognitive impairment. Group comparisons will be performed using the Chi-square test, independent t test, Mann-Whitney U test, ANOVA test, and multiple linear regression, where appropriate.
Anticipation In this project, we will be able to explore the distribution patterns of amyloid plaque and tau protein among dementia patients with different etiologies, and also evaluate their influence on cognition
- Being tested
- PMPBB3, AV45
- Keywords
- Vascular cognitive impairment, Alzheimer's disease, fronto-temporal dementia, amyloid plaque, tau protein
- Medical subject headings
- Alzheimer Disease, Plaque, Amyloid, 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
AV45Drug
F-18 AV45 PET Imaging
| Study group | Role | What they receive |
|---|---|---|
| PMPBB3 | Other | 1. Primary endpoint(s):
A. To determine the distribution patterns of cerebral amyloid plaques and Tau protein among AD/MCI, VCI and FTP patients as well as normal controls.
2. Secondary endpoints:
A. To correlate vascular burden, [18F]AV45 and [18F]MNI-958(PMPBB3) retention with clinical presentation and cognitive performance among different groups of subjects B. To determine the impacts of vascular burden, [18F]AV45 and [18F]MNI-958(PMPBB3) retention changes on cognitive trajectory over the 18-month follow-up period. Receives: Drug: PMPBB3; Drug: AV45 |
| AV45 | Other | 1. Primary endpoint(s):
A. To determine the distribution patterns of cerebral amyloid plaques and Tau protein among AD/MCI, VCI and FTP patients as well as normal controls.
2. Secondary endpoints:
A. To correlate vascular burden, [18F]AV45 and [18F]MNI-958(PMPBB3) retention with clinical presentation and cognitive performance among different groups of subjects B. To determine the impacts of vascular burden, [18F]AV45 and [18F]MNI-958(PMPBB3) retention changes on cognitive trajectory over the 18-month follow-up period. Receives: Drug: PMPBB3; Drug: AV45 |
What is being measured
The primary outcome is the main question the study is designed to answer.
The Clinical Dementia Rating-Sum of Boxes (CDR-SB) change score
The Clinical Dementia Rating-Sum of Boxes (CDR-SB) change score between baseline and 18-month follow-up will be calculated for primary endpoint determination. Two-sample independent t-test will be performed to compare the CDR-SB change score between patients positive and negative for tau protein accumulation. Patients will be stratified into tau-positive and tau-negative groups, and the presentations of their cognitive state will be recorded at the 18-month follow-up visit.
Measured: through study completion, an average of 1.5 year
Chi-square test will be performed to analyze dementia conversion rate.
Measured: through study completion, an average of 1.5 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Mar 2020
- Study start21 Sep 2018
- Primary completion18 May 2024 (estimated)
- Study completion30 Nov 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Vascular Cognitive Impairment, Alzheimer's Disease, Fronto-temporal DementiaStudies 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 vascular cognitive impairment (VCI), n=80. B. Group B: Alzheimer's disease/mild cognitive impairment (MCI), n=80. C. Group C: Fronto-temporal dementia (FTD), n=30. D. Group D: Normal control, n=30. E. Group E: progressive supranuclear palsy(PSP), n=80.
- Masking
- Single blind
- Who is masked
- Investigator
- Enrolment
- 220 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Chang Gung Memorial Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Huang Kuo-Lun, M.D., Study chair, Stroke Section, Department of Neurology, Chang-Gung memorial Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04309253
- Sponsor's protocol ID
- 201800984A0
- 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 Vascular Burden, Amyloid Plaque and Tau Protein in Patients With Vascular Cognitive Impairment and Dementia With Tauopathy
- ClinicalTrials.gov ID
- NCT04309253
- Acronym / sponsor ID
- 201800984A0
- Keywords
- Vascular cognitive impairment, Alzheimer's disease, fronto-temporal dementia, amyloid plaque, tau protein
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 220 participants (estimated)
- Lead sponsor
- Chang Gung Memorial HospitalUniversity, hospital or other
- Study start
- 21 Sep 2018 (actual)
- Primary completion
- 18 May 2024 (estimated)
- Study completion
- 30 Nov 2025 (estimated)
- First posted
- 16 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 Amyloid plaques and tau protein are the landmarks of neurodegeneration in Alzheimer's disease (AD). On the other hand, it is reported that cerebral ischemia may induce amyloid plaques and tau protein accumulation. However, it was difficult to in vivo disentangle the complex and dynamic interactions between AD pathophysiology and cerebral vascular injury during the post-stroke cognitive impairment development in the past. With the advent of novel radiotracers specific to cerebral amyloid plaques and tau protein, we aim to conduct a prospective multimodal neuroimaging cohort study to investigate the contribution of vascular injury, amyloid plaque and tau protein to cognitive impairment.
Subjects and methods The prospective project plans to recruit patients with vascular cognitive impairment (VCI) (Group A, n=80), Alzheimer's disease/mild cognitive impairment (MCI) (Group B, n = 120), fronto-temporal dementia (FTD) (Group C, n =30), and progressive supranuclear palsy (PSP) (Group E, n = 80). In addition, another 30 healthy people will be recruited as the control group (Group D, n=30). [18F]AV45 and [18F]MNI-958(PMPBB3) PET will be done for imaging cerebral amyloid plaque and tau protein distribution, brain MRI for obtaining structural and functional information, and neuropsychological tests for cognitive performance. Cognitive evaluation will be repeated 18 months after recruitment. In addition, APOE genotyping 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]AV-45 and [18F]MNI-958(PMPBB3) PET, the study will be able to investigate the composite influence of cerebrovascular disease and neurodegenerative pathology on the trajectory of cognitive impairment. Group comparisons will be performed using the Chi-square test, independent t test, Mann-Whitney U test, ANOVA test, and multiple linear regression, where appropriate.
Anticipation In this project, we will be able to explore the distribution patterns of amyloid plaque and tau protein among dementia patients with different etiologies, and also evaluate their influence on cognition
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 vascular cognitive impairment (VCI), n=80. B. Group B: Alzheimer's disease/mild cognitive impairment (MCI), n=80. C. Group C: Fronto-temporal dementia (FTD), n=30. D. Group D: Normal control, n=30. E. Group E: progressive supranuclear palsy(PSP), n=80.
| Arm | Type | Receives |
|---|---|---|
| PMPBB3 | Other | Drug: PMPBB3, Drug: AV451. Primary endpoint(s): A. To determine the distribution patterns of cerebral amyloid plaques and Tau protein among AD/MCI, VCI and FTP patients as well as normal controls. 2. Secondary endpoints: A. To correlate vascular burden, [18F]AV45 and [18F]MNI-958(PMPBB3) retention with clinical presentation and cognitive performance among different groups of subjects B. To determine the impacts of vascular burden, [18F]AV45 and [18F]MNI-958(PMPBB3) retention changes on cognitive trajectory over the 18-month follow-up period. |
| AV45 | Other | Drug: PMPBB3, Drug: AV451. Primary endpoint(s): A. To determine the distribution patterns of cerebral amyloid plaques and Tau protein among AD/MCI, VCI and FTP patients as well as normal controls. 2. Secondary endpoints: A. To correlate vascular burden, [18F]AV45 and [18F]MNI-958(PMPBB3) retention with clinical presentation and cognitive performance among different groups of subjects B. To determine the impacts of vascular burden, [18F]AV45 and [18F]MNI-958(PMPBB3) retention changes on cognitive trajectory over the 18-month follow-up period. |
Who may qualify
- Ages
- 20 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (23 listed)
- Inclusion criteria for VCI (Group A, n=80)
- Inclusion criteria for AD / MCI (Group B, n=120)
- Inclusion criteria for FTD (Group C, n=30)
- Inclusion criteria for normal control (Group D, n=30)
- Inclusion criteria for PSP (Group E, n=80)
Key exclusion criteria (7 listed)
- Life expectancy less than 1 year.
- Clinically significant abnormal laboratory values (such as AST/ALT >= 3X of upper normal limits).
- Clinically significant or unstable medical or psychiatric illness.
- Epilepsy history.
- Cognitive impairment resulting from trauma or brain damage.
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 | AV45, PMPBB3 |
| AV45F-18 AV45 PET Imaging | Drug | AV45, PMPBB3 |
Primary outcome
The Clinical Dementia Rating-Sum of Boxes (CDR-SB) change score
Time frame: through study completion, an average of 1.5 year
The Clinical Dementia Rating-Sum of Boxes (CDR-SB) change score between baseline and 18-month follow-up will be calculated for primary endpoint determination. Two-sample independent t-test will be performed to compare the CDR-SB change score between patients positive and negative for tau protein accumulation. Patients will be stratified into tau-positive and tau-negative groups, and the presentations of their cognitive state will be recorded at the 18-month follow-up visit.
Chi-square test will be performed to analyze dementia conversion rate.
Time frame: through study completion, an average of 1.5 year
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.
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.
Huang Kuo-Lun, M.D. study chair
Stroke Section, Department of Neurology, Chang-Gung memorial Hospital
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 AV45 in people with Vascular Cognitive Impairment, Alzheimer's Disease, Fronto-temporal Dementia, 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 23 inclusion and 7 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?
The Clinical Dementia Rating-Sum of Boxes (CDR-SB) change score (time frame: through study completion, an average of 1.5 year). The study lists 2 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.