Diagnostic Imaging for Tauopathies

Overseen By Refatun Momo

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: University of Pennsylvania

Disqualifiers: Pregnancy, Schizophrenia, Bipolar, Alcohol abuse, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

94 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This current protocol will provide the key data to help determine the specificity of our to-be-developed radiotracers by implementing a multi-site diagnostic assessment core and PET imaging of A-beta amyloid (may be completed at some sites as part of another protocol) that is commonly deposited in the brains of people with Parkinson's Disease (PD), Multiple System Atrophy (MSA), Progressive Supranuclear Palsy (PSP) or Frontotemporal Dementia (FTD) as well as healthy controls. This multicenter U19 grant is centered at U Pennsylvania (U Penn) (PI: Robert Mach) in collaboration with U Pittsburgh (Pitt), Yale University, U of California at San Francisco (UCSF) and Washington University in St. Louis (WU). U Penn will act as the single IRB of Record (sIRB) for this multi-center project and subjects will be recruited from all sites.

Will I have to stop taking my current medications?

The trial protocol does not specify whether participants must stop taking their current medications. It is best to discuss this with the study team or your doctor.

Is diagnostic imaging for tauopathies, like Amyloid PET scans and Brain MRI, safe for humans?

Amyloid PET imaging, used to detect amyloid-beta in the brain, has been approved by the FDA since 2012 and is considered a non-invasive and safe technique for diagnosing Alzheimer's disease and other conditions. It is widely used in clinical practice and research, with no significant safety concerns reported in the studies reviewed. ^{1 2 3 4 5}

How is the diagnostic imaging treatment for tauopathies different from other treatments?

The diagnostic imaging treatment for tauopathies is unique because it uses advanced imaging techniques like PET scans to visualize tau deposits in the brain, which helps in early and accurate diagnosis. Unlike traditional treatments that focus on managing symptoms, this approach aids in identifying the specific type of neurodegenerative disease, potentially leading to more targeted interventions. ^{4 6 7 8 9}

What data supports the effectiveness of the treatment Amyloid PET scan for diagnosing tauopathies?

Amyloid PET scans are effective in identifying amyloid-positive patients, which is useful for early-stage Alzheimer's disease diagnosis and clinical trial enrollment. This imaging technique helps in detecting early cerebral amyloidosis, a key feature of Alzheimer's, and can improve diagnostic confidence and patient management. ^{2 4 10 11 12}

Are You a Good Fit for This Trial?

This trial is for adults aged 40-85 with Parkinson's Disease, Multiple System Atrophy, Progressive Supranuclear Palsy, Frontotemporal Dementia or healthy controls. They must understand the study and consent to participate. Pregnant women and those with major psychiatric disorders or substance abuse issues are excluded.

Inclusion Criteria

Participants must be willing to participate in the study in accordance with institutional and federal guidelines

Participants must be informed of the investigational nature of the study and be willing to provide written informed consent

A group of experts will decide if you have a specific brain condition (PD, MSA, PSP, FTD) or if you are a healthy control.

Exclusion Criteria

You have a serious mental illness like schizophrenia or bipolar disorder.

Contraindications or inability to tolerate imaging, arterial line or IV placement or blood draw procedures in the opinion of an investigator or treating physician

I am not pregnant or breastfeeding.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Diagnostic Assessment

Subjects may receive a brain MRI and neurological exam with diagnostic assessments

8 weeks

Multiple visits for imaging and assessments

Follow-up

Participants are monitored for safety and effectiveness after diagnostic assessments

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Amyloid PET scan
• Brain MRI Scan
• Neurologic exam

Trial Overview The trial tests new radiotracers' specificity using diagnostic assessments like neurologic exams and brain scans (Amyloid PET and MRI) across multiple sites including U Penn, Pitt, Yale University, UCSF, and WU.

How Is the Trial Designed?

Group I: Diagnostic Assessments Experimental Treatment 2 Interventions

Subjects may receive a brain MRI and neurological exam with diagnostic assessments.

Who Is Running the Clinical Trial?

University of Pennsylvania

Lead Sponsor

Trials

2,118

Recruited

45,270,000+

Published Research Related to This Trial

In a phase 1b trial involving 278 patients with early stages of Alzheimer's disease, amyloid PET imaging successfully identified 61% of patients as amyloid-positive, making it a promising tool for selecting participants for clinical trials.

The study found that ApoE ε4 carriers were more likely to be amyloid-positive (80%) compared to noncarriers (43%), highlighting the potential of PET imaging to enrich trial populations based on genetic risk factors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Amyloid PET Screening for Enrichment of Early-Stage Alzheimer Disease Clinical Trials: Experience in a Phase 1b Clinical Trial. Sevigny, J., Suhy, J., Chiao, P., et al.[2022]

Amyloid PET imaging can lead to significant changes in the diagnosis of Alzheimer's disease, with a pooled estimate showing a 31% change rate across 16 studies involving various patient populations.

The imaging technique also increases diagnostic confidence and influences patient management decisions, particularly in cases where there is high diagnostic uncertainty, affecting treatment plans for Alzheimer's medications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Review of Diagnostic Impact of Amyloid Positron Emission Tomography Imaging in Clinical Practice. Kim, Y., Rosenberg, P., Oh, E.[2019]

Human amyloid imaging using PET scans allows for the detection of early cerebral amyloidosis, a key feature of Alzheimer's disease, potentially leading to earlier diagnosis.

While initial data is promising, it is important to interpret amyloid PET results carefully, as the presence of amyloidosis does not necessarily indicate clinical Alzheimer's disease or predict immediate cognitive decline.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Amyloid imaging of Alzheimer's disease using Pittsburgh Compound B. Johnson, KA.[2019]

A systematic review of 10 papers from 7 studies found that disclosing amyloid PET scan results generally did not lead to increased depression among individuals with cognitive impairment, but those with mild cognitive impairment and high amyloid levels experienced more distress or anxiety.

While participants remembered their scan results, it remains uncertain if this improved their understanding of their diagnosis, indicating a need for further research on the psychosocial impacts of amyloid PET scans.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Psychosocial and Behavioral Outcomes for Persons With Cognitive Impairment and Caregivers Following Amyloid-β PET Scan Disclosure: A Systematic Review. Couch, E., Ashford, MT., Zhang, W., et al.[2023]

Amyloid PET (aPET) imaging led to a revision of diagnoses in 31.3% of cases among cognitively impaired subjects, significantly higher than the 3.2% revision rate in control patients with delayed feedback, indicating its strong impact on diagnostic accuracy.

Following aPET, 62.1% of patients experienced increased diagnostic confidence, and 72.2% had changes in management plans, highlighting its effectiveness in improving patient care and treatment strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Systematic Review and Aggregated Analysis on the Impact of Amyloid PET Brain Imaging on the Diagnosis, Diagnostic Confidence, and Management of Patients being Evaluated for Alzheimer's Disease. Fantoni, ER., Chalkidou, A., O' Brien, JT., et al.[2023]

Amyloid imaging, particularly using Pittsburgh Compound-B (PIB) with PET scans, is a highly sensitive method for detecting amyloid-beta accumulation in the brain, which can serve as an early biomarker for Alzheimer's disease (AD).

This imaging technique not only aids in the early diagnosis of AD but also helps monitor the effectiveness of treatments aimed at reducing amyloid-beta levels, and can differentiate AD from other neurodegenerative disorders.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Amyloid imaging]. Ishii, K.[2016]

Recent advancements in positron emission tomography (PET) allow for the in vivo detection of beta-amyloid (Aβ) pathology, with fluorine-18 labeled radiopharmaceuticals becoming the preferred choice over carbon-11 labeled Pittsburgh compound B for clinical use.

Amyloid imaging is recommended for evaluating patients with mild cognitive impairment or atypical dementia, but its use in asymptomatic individuals is currently discouraged due to uncertainty in prognosis, despite the potential for elevated Aβ levels to indicate preclinical Alzheimer's disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Use of amyloid PET across the spectrum of Alzheimer's disease: clinical utility and associated ethical issues. Leuzy, A., Zimmer, ER., Heurling, K., et al.[2020]

Human amyloid imaging has advanced significantly, starting from the use of Thioflavin T derivatives as PET tracers to the FDA approval of Florbetapir in 2012, which allows for in vivo diagnosis of Alzheimer's disease (AD).

While amyloid PET imaging is a promising tool for detecting β-amyloid pathology in the brain, it is important to note that it serves as a surrogate marker and does not directly diagnose Alzheimer's disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Amyloid imaging: the court of public opinion. Lerner, AJ.[2018]

Amyloid imaging is a non-invasive method that allows researchers to see how amyloid beta builds up in the brains of living people, which is crucial for studying early Alzheimer's disease.

This imaging technique has become essential for both observational and interventional studies of Alzheimer's, especially as new disease-modifying drugs are developed, although its current clinical use is mainly for diagnosing atypical dementia cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Amyloid imaging]. Ishii, K.[2016]

Recent advances in amyloid PET imaging have improved the ability to diagnose Alzheimer's disease and related dementias, providing valuable insights into brain structure and function.

Current guidelines recommend the use of amyloid PET imaging for patients with cognitive complaints, highlighting its potential clinical value in early detection and management of Alzheimer's disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Role of Neuroimaging in the Assessment of the Cognitively Impaired Elderly. Kollack-Walker, S., Liu, CY., Fleisher, AS.[2018]

Current imaging techniques, such as PET and MRI, can help identify different subtypes of Alzheimer's disease (AD) and differentiate them from other neurodegenerative diseases, potentially at an early stage.

While amyloid PET is useful for early detection of AD, it does not differentiate between subtypes; however, tau and glucose PET, along with MRI, can reveal specific patterns of pathology associated with different AD subtypes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Imaging Clinical Subtypes and Associated Brain Networks in Alzheimer's Disease. Herholz, K.[2022]

Amyloid PET imaging is a valuable tool for the early and accurate diagnosis of Alzheimer's disease by evaluating the amyloid-β pathology, which is a key biomarker for the disease.

The article emphasizes the importance of proper administration, scanning techniques, and image analysis methods for amyloid PET, aiming to enhance its reliability in clinical settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Technical Considerations on Scanning and Image Analysis for Amyloid PET in Dementia. Akamatsu, G., Ohnishi, A., Aita, K., et al.[2017]

Citations

1. United States pubmed.ncbi.nlm.nih.gov

Amyloid PET Screening for Enrichment of Early-Stage Alzheimer Disease Clinical Trials: Experience in a Phase 1b Clinical Trial. [2022]

2. Switzerland pubmed.ncbi.nlm.nih.gov

A Review of Diagnostic Impact of Amyloid Positron Emission Tomography Imaging in Clinical Practice. [2019]

3. United States pubmed.ncbi.nlm.nih.gov

Amyloid imaging of Alzheimer's disease using Pittsburgh Compound B. [2019]

4. United States pubmed.ncbi.nlm.nih.gov

Psychosocial and Behavioral Outcomes for Persons With Cognitive Impairment and Caregivers Following Amyloid-β PET Scan Disclosure: A Systematic Review. [2023]

5. Netherlands pubmed.ncbi.nlm.nih.gov

A Systematic Review and Aggregated Analysis on the Impact of Amyloid PET Brain Imaging on the Diagnosis, Diagnostic Confidence, and Management of Patients being Evaluated for Alzheimer's Disease. [2023]

6. Japan pubmed.ncbi.nlm.nih.gov

[Amyloid imaging]. [2016]

7. England pubmed.ncbi.nlm.nih.gov

Use of amyloid PET across the spectrum of Alzheimer's disease: clinical utility and associated ethical issues. [2020]

8. United States pubmed.ncbi.nlm.nih.gov

Amyloid imaging: the court of public opinion. [2018]

9. Japan pubmed.ncbi.nlm.nih.gov

[Amyloid imaging]. [2016]

10. United States pubmed.ncbi.nlm.nih.gov

The Role of Neuroimaging in the Assessment of the Cognitively Impaired Elderly. [2018]

11. Switzerland pubmed.ncbi.nlm.nih.gov

Imaging Clinical Subtypes and Associated Brain Networks in Alzheimer's Disease. [2022]

12. Japan pubmed.ncbi.nlm.nih.gov

Technical Considerations on Scanning and Image Analysis for Amyloid PET in Dementia. [2017]