Tau Imaging with F-18 AV 1451 for Progressive Supranuclear Palsy

Recruiting in Palo Alto (17 mi)

Overseen by Jennifer Whitwell, PhD

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Academic

Recruiting

Sponsor: Mayo Clinic

Must not be taking: Chemotherapy

Disqualifiers: Alzheimer's, Parkinson's, Strokes, others

No Placebo Group

Approved in 2 Jurisdictions

Trial Summary

What is the purpose of this trial?

This study is designed to learn more about overall tau burden in the brain of patients with Progressive Supranuclear Palsy (PSP).

Do I need to stop my current medications for the trial?

The trial does not specify if you need to stop your current medications, but you may be excluded if you are on medications that might affect brain structure or metabolism, like chemotherapy.

What data supports the effectiveness of the drug F-18 AV 1451 for Progressive Supranuclear Palsy?

The drug F-18 AV 1451, also known as 18F-flortaucipir, is used to visualize tau protein buildup in the brain. While it is effective in detecting tau in Alzheimer's disease, its effectiveness in Progressive Supranuclear Palsy (PSP) is less clear, with studies showing mixed results in distinguishing PSP from other conditions like Parkinson's disease. ^{1 2 3 4 5}

Is F-18 AV 1451 (Tauvid) safe for humans?

F-18 AV 1451, also known as Tauvid or Flortaucipir F-18, has been used in PET imaging to study tau protein in the brain, primarily for Alzheimer's disease. Studies have focused on its ability to detect tau pathology, and while specific safety data is not detailed in the provided research, its use in multiple studies suggests it is generally considered safe for human use in imaging. ^{1 2 4 5 6}

How does the drug 18 F-AV-1451 differ from other treatments for progressive supranuclear palsy?

The drug 18 F-AV-1451 is unique because it is a radiotracer used for imaging, allowing doctors to visualize and measure tau protein buildup in the brain, which is a key feature of progressive supranuclear palsy. Unlike other treatments that may focus on symptom management, this drug helps in diagnosing and understanding the disease's progression by highlighting tau pathology. ^{1 2 3 4 5}

Research Team

Jennifer Whitwell, PhD

Principal Investigator

Mayo Clinic

Eligibility Criteria

This trial is for adults over 35 with Progressive Supranuclear Palsy (PSP) symptoms and a diagnosis of possible or probable PSP. Participants need an informant to provide additional information about their functioning. Exclusions include pregnancy, other neurodegenerative diseases, conditions that mimic PSP symptoms, certain genetic conditions increasing cancer risk, contraindications to MRI, severe claustrophobia, and unstable medical conditions.

Inclusion Criteria

Must have an informant or study partner that can provide independent information of functioning

I am over 35 and my PSP symptoms are getting worse slowly.

I have been diagnosed with Progressive Supranuclear Palsy.

Exclusion Criteria

I do not have any other neurodegenerative diseases besides possible PSP.

I do not have genetic conditions like Cowden, Lynch syndrome, or Down's syndrome.

I do not have illnesses like brain injury, encephalitis, strokes, or developmental syndromes.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Imaging

Participants receive a Tau PET scan to assess tau burden in the brain

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after imaging

4 weeks

Treatment Details

Interventions

• F-18 AV 1451 (Molecular Imaging Agent)

Trial Overview The study tests the imaging agent F-18 AV 1451 to measure tau protein accumulation in the brain of patients with PSP. It aims to understand the overall burden of tau in these patients using advanced imaging techniques.

Participant Groups

Group I: Tau PET Scan, F-18 AV 1451 Experimental Treatment 1 Intervention

All subjects will received a Tau PET scan.

Who Is Running the Clinical Trial?

Mayo Clinic

Lead Sponsor

Trials

3,427

Recruited

3,221,000+

Dr. Gianrico Farrugia

Mayo Clinic

Chief Executive Officer since 2019

MD from University of Malta Medical School

Dr. Richard Afable

Mayo Clinic

Chief Medical Officer

MD from Loyola Stritch School of Medicine

Findings from Research

The FDA-approved radiotracer 18F-flortaucipir is increasingly used in PET imaging to visualize tau pathology in patients with cognitive impairment, particularly Alzheimer's disease.

An international consensus has been established to standardize the procedural use of 18F-flortaucipir PET imaging, which will enhance its application in clinical practice for diagnosing and managing Alzheimer's disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

International consensus on the use of tau PET imaging agent 18F-flortaucipir in Alzheimer's disease. Tian, M., Civelek, AC., Carrio, I., et al.[2022]

In a study involving 10 patients with progressive supranuclear palsy (PSP) and 60 controls, the [18 F]AV-1451 PET ligand showed elevated signals in specific brain regions associated with PSP, indicating its potential for in vivo assessment of tau pathology in this condition.

The regional distribution of [18 F]AV-1451 uptake in PSP was distinct from that in Alzheimer's dementia, with higher signals in the pallidum and midbrain for PSP, while Alzheimer's showed greater cortical signals, suggesting different underlying tau pathology in these diseases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[18 F]AV-1451 tau positron emission tomography in progressive supranuclear palsy. Whitwell, JL., Lowe, VJ., Tosakulwong, N., et al.[2022]

In a study involving 14 patients with progressive supranuclear palsy (PSP), 18F-AV-1451 PET imaging revealed distinct subcortical binding patterns indicative of tau pathology, particularly in areas like the putamen and globus pallidus, compared to healthy controls.

However, the study found no correlation between the levels of 18F-AV-1451 binding and the severity of motor dysfunction in PSP patients, suggesting that this imaging technique may not be ideal for assessing tau pathology in relation to clinical symptoms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Subcortical 18 F-AV-1451 binding patterns in progressive supranuclear palsy. Cho, H., Choi, JY., Hwang, MS., et al.[2022]

C9orf72 expansion carriers showed increased tau accumulation in the entorhinal cortex as measured by AV-1451 PET imaging, indicating a potential link to primary age-related tauopathy.

Despite the increased tau uptake, there was no correlation between AV-1451 accumulation and clinical severity, disease duration, or cognitive performance in the studied individuals.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tau positron emission tomography imaging in C9orf72 repeat expansion carriers. Ly, CV., Koenig, L., Christensen, J., et al.[2020]

In a study involving 33 patients with progressive supranuclear palsy (PSP), 18 F-flortaucipir showed significantly elevated uptake in specific brain regions compared to normal controls (46 participants) and patients with Parkinson disease (26 participants), indicating its potential as a biomarker for tau pathology in PSP.

The globus pallidus region was particularly effective in distinguishing PSP patients from both controls and Parkinson disease patients, with high accuracy (AUC values of 0.872 and 0.893, respectively), suggesting that 18 F-flortaucipir could aid in the diagnosis of PSP.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

18 F-flortaucipir tau positron emission tomography distinguishes established progressive supranuclear palsy from controls and Parkinson disease: A multicenter study. Schonhaut, DR., McMillan, CT., Spina, S., et al.[2022]

The radiation dose from the PET radioligand [(18)F]AV-1451 was estimated to be 4.7 mSv for a standard injection of 185 MBq, indicating a manageable level of exposure for healthy subjects.

The liver was identified as the critical organ for radiation burden, but the overall effective dose suggests that multiple PET scans using [(18)F]AV-1451 could be safely performed within a year.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Human Radiation Dosimetry of [(18)F]AV-1451(T807) to Detect Tau Pathology. Choi, JY., Lyoo, CH., Lee, JH., et al.[2022]

References

1. Germany pubmed.ncbi.nlm.nih.gov

International consensus on the use of tau PET imaging agent 18F-flortaucipir in Alzheimer's disease. [2022]

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

[18 F]AV-1451 tau positron emission tomography in progressive supranuclear palsy. [2022]

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

Subcortical 18 F-AV-1451 binding patterns in progressive supranuclear palsy. [2022]

4. England pubmed.ncbi.nlm.nih.gov

Tau positron emission tomography imaging in C9orf72 repeat expansion carriers. [2020]

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

18 F-flortaucipir tau positron emission tomography distinguishes established progressive supranuclear palsy from controls and Parkinson disease: A multicenter study. [2022]

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

Human Radiation Dosimetry of [(18)F]AV-1451(T807) to Detect Tau Pathology. [2022]