Establishing 18F PMPBB3 (APN 1607) PET Imaging Markers for Diagnosis of Tauopathy Parkinsonism Syndromes

Last updated: October 15, 2024
Sponsor: National Taiwan University Hospital
Overall Status: Completed

Phase

N/A

Condition

Dyskinesias

Treatment

18F-PMPBB3 (APN-1607) PET imaging

Clinical Study ID

NCT04557865
202006181MINB
  • Ages 20-90
  • All Genders
  • Accepts Healthy Volunteers

Study Summary

Parkinson's disease (PD) is one of the most common neurodegenerative disorders. The diagnosis of PD is primarily based on clinical presentations while the pathology stage of a-synuclein containing Lewy body deposition has already advanced. In addition to PD, there is another group of patients presenting with parkinsonism features mixed with other neurodegenerative symptoms. Pathologically, patients with these PD-mimicking parkinsonism syndromes, such as progressive supranuclear palsy (PSP), corticobasal degeneration disorders (CBGD) and frontotemporal dementia (FTD) with/without parkinsonism, have 4 repeat paired helical filament forms of tau protein (4R PHF-tau) aggregations in the neurons. Patients with these tauopathy related parkinsonism-plus syndromes could initially present as PD symptoms but will have a more deliberating disease course and combine with other systems degeneration. These patients are often a substantial diagnostic challenge to clinicians. Therefore, there is an urgent need to develop reliable imaging and biofluid biomarkers for differentiating patients with PD and variable parkinsonism-plus syndromes.

Recently, new generation of novel radiotracer 18F-PMPBB3 (APN-1607), which can be labeled with 4R PHF-tau without significant off-target binding, has been successfully developed. Therefore, this study will enroll 150 participants, including 30 healthy controls, 30 PD patients, and 60 patients with different parkinsonism-plus syndromes (including 10 patients with multiple system atrophy, 10 patients with progressive supranuclear palsy, 10 patients with cortical basal syndrome and 30 patients with frontotemporal dementia), and 30 patients with mild cognitive decline (MCI) or Alzheimer's disease (AD). All participants will receive complete neurological examination, 18F-PMPBB3 (APN-1607) PET, brain MRI scans, plasma markers for total/phosphorylated tau, a-synuclein and Ab42/Ab40 and genetic markers covering MAPT、SNCA、LRRK2、GBA and APOE genes. We aim to explore:

  1. Whether 18F-PMPBB3 (APN-1607) can differentiate patients with tauopathy (PSP, CBGD, FTD, MCI and AD) and synucleinopathy (PD, MSA).

  2. Whether the distribution of tau deposition detected by 18F-PMPBB3 (APN-1607) correlate to disease severity, progression, and prognosis in patients with tauopathy.

  3. Whether the loading of tau deposition detected by 18F-PMPBB3 (APN-1607) correlate to plasma levels of total/phosphorylated tau.

  4. Determine specific genetic susceptibility sub-groups are more vulnerable to tau deposition detected by 18F-PMPBB3 (APN-1607) in patients with tauopathy.

The research results will help to understand the potential of 18F-PMPBB3 (APN-1607) as an imaging biomarker for diagnosis, severity and therapeutic assessment tool for patients with tauopathy.

Eligibility Criteria

Inclusion

Inclusion Criteria:

  1. Written informed consent must be obtained before any assessment is performed.

  2. Patients fulfill the criteria of United Kingdom Brain Bank Diagnostic Criteria of "possible" or "probably" PD.

  3. Patients fulfill the criteria of MDS consensus criteria of "possible" or "probably"MSA.

  4. Patients fulfill the criteria of NINDS-SPSP clinical criteria for the diagnosis ofPSP "as possible" or "probably" PSP, and healthy volunteer with no clinicallyrelevant finding on physical examination at screening visit.

  5. Patients fulfill the criteria of Work Group on Frontotempotal Dementia and Pick'sDisease of "possible" or "probably" FTD.

  6. Patients fulfill the Armstrong's criteria of "possible" or "probably" CBGD.

  7. Patients fulfill the National Institute on Aging-Alzheimer's Association (NIA-AA)workgroup for clinical diagnostic guidelines (NIA-AA-C) for MCI.

  8. Patients fulfill the National Institute on Aging-Alzheimer's Association (NIA-AA)workgroup for clinical diagnostic guidelines (NIA-AA-C) for AD.

  9. Neurologically normal controls.

  10. Age range 20-90 years

Exclusion

Exclusion Criteria:

  1. Implantation of metal devices including cardiac pacemaker, intravascular metaldevices.

  2. Major systemic diseases including coronary arterial disease, heart failure, uremia,hepatic failure, prominent strokes, acute myocardial infarction, poorly controlleddiabetes, previous head injury, intracranial operation, hypoxia, sepsis or severeinfectious diseases

  3. Major psychiatric disorders, drug or alcohol abuse and major depression

  4. Pregnant women or breast- feeding women

Study Design

Total Participants: 68
Treatment Group(s): 1
Primary Treatment: 18F-PMPBB3 (APN-1607) PET imaging
Phase:
Study Start date:
January 31, 2022
Estimated Completion Date:
September 02, 2024

Connect with a study center

  • National Taiwan University Hospital

    Taipei,
    Taiwan

    Site Not Available

Not the study for you?

Let us help you find the best match. Sign up as a volunteer and receive email notifications when clinical trials are posted in the medical category of interest to you.