AV-1451 Imaging for Apraxia of Speech

Overseen By Sarah Boland, CCRP

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: Mayo Clinic

Must not be taking: Chemotherapy

Disqualifiers: Traumatic brain injury, Strokes, Pregnancy, others

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

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 1

50 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how changes in the brain relate to speech and language issues in individuals with neurodegenerative apraxia of speech (AOS). The study uses a Tau PET scan to examine the involvement of a protein called Tau. This scan employs AV-1451 (also known as Flortaucipir F 18 or T807), a tracer that helps visualize Tau protein in the brain. Participants must have been diagnosed with AOS at the Mayo Clinic and should not have other conditions, such as a brain injury or stroke, that could explain their speech issues. As a Phase 4 trial, this research aims to understand how an already FDA-approved treatment benefits more patients.

Will I have to stop taking my current medications?

The trial excludes participants who are on medications that might affect brain structure or metabolism, such as chemotherapy. If you are taking such medications, you may need to stop them to participate.

What is the safety track record for AV-1451?

Research has shown that AV-1451, also known as Flortaucipir F-18, is generally safe for most people. Studies have found that the most common side effects are minor, such as injection site reactions, mild headaches, or dizziness. However, a small chance of more serious allergic reactions exists.

Researchers are using AV-1451 to study brain changes in conditions like apraxia of speech. It has also been used in other studies involving different brain conditions, providing some confidence in its safety for humans. However, the safety and effectiveness of AV-1451 for this specific use are still under investigation. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Researchers are excited about the use of AV-1451 for apraxia of speech because it offers a new way to visualize tau protein deposits in the brain, which are thought to contribute to this condition. Unlike existing treatments that may focus on managing symptoms, AV-1451 uses tau PET imaging to directly assess the tau burden. This innovative approach could lead to a better understanding of the disease mechanism and potentially pave the way for more targeted therapies in the future.

What evidence suggests that AV-1451 is effective for neurodegenerative apraxia of speech?

Research has shown that AV-1451, also known as Flortaucipir F 18, can track disease progression in primary progressive apraxia of speech (PPAOS). In this trial, all participants will undergo a Tau PET scan using AV-1451 to assess tau burden in the brain. This imaging agent highlights areas where tau, a protein that can harm brain cells, accumulates. High levels of tau have been found in patients with PPAOS. This buildup helps identify how the disease affects the brain over time, aiding doctors in understanding and monitoring the condition more effectively. ^{1 6 7 8 9}

Who Is on the Research Team?

Jennifer Whitwell, PhD

Principal Investigator

Mayo Clinic

Are You a Good Fit for This Trial?

This trial is for individuals diagnosed with neurodegenerative apraxia of speech (AOS) at Mayo Clinic. It's not suitable for those with severe claustrophobia, pregnant or breastfeeding women, people on certain medications like chemotherapy, those with metal implants that affect MRI scans, brain structure abnormalities, or other illnesses causing speech issues.

Inclusion Criteria

Subjects that fulfill clinical inclusion criteria for neurodegenerative AOS that have been seen and diagnosed at Mayo Clinic

Exclusion Criteria

I have a condition like a stroke or brain injury that affects my speech.

I do not have any brain conditions that could affect imaging results.

All women who can become pregnant must have a pregnancy test no more than 48 hours before the PET scan

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Imaging and Assessment

Participants undergo Tau PET scan and multi-modality neuroimaging to assess Tau burden and other neurodegenerative markers

1-2 days

1 visit (in-person)

Longitudinal Monitoring

Participants are monitored for changes in neuroimaging, speech and language, neurological, and neuropsychological assessments

Ongoing

Follow-up

Participants are monitored for safety and effectiveness after initial assessments

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• AV-1451

Trial Overview The study focuses on the drug AV-1451 to explore how changes in brain structure and function relate to the progression of AOS. Participants will undergo various imaging tests over time to track these changes and their impact on speech and language abilities.

How Is the Trial Designed?

Group I: Tau positron emission tomography (PET) Experimental Treatment 1 Intervention

All subjects will receive Tau PET scan on approximately day 1 or day 2 of study to assess Tau burden in the brain.

Who Is Running the Clinical Trial?

Mayo Clinic

Lead Sponsor

Trials

3,427

Recruited

3,221,000+

National Institute on Deafness and Other Communication Disorders (NIDCD)

Collaborator

Trials

377

Recruited

190,000+

Published Research Related to This Trial

Children with childhood apraxia of speech (CAS) exhibit significant motor and behavioral problems, with assessments showing that their oral motor functions are notably below average, indicating a potential global motor deficit.

The study of 18 children revealed that many had co-occurring difficulties in overall and manual motor functions and adaptive behavior, suggesting that these issues may contribute to the undiagnosed developmental challenges often seen in CAS.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Motor functions and adaptive behaviour in children with childhood apraxia of speech. Tükel, Ş., Björelius, H., Henningsson, G., et al.[2015]

Patients with primary progressive apraxia of speech (PPAOS) demonstrated significantly slower diadochokinetic (DDK) speech rates compared to healthy controls, indicating that DDK tasks can help differentiate between these groups.

Slower DDK rates were linked to greater severity of speech apraxia and were associated with reduced brain metabolism in specific areas, suggesting a potential mechanism for the speech difficulties observed in PPAOS.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Acoustic Analysis and Neuroimaging Correlates of Diadochokinetic Rates in Mild-Moderate Primary Progressive Apraxia of Speech. Josephs, KA., Duffy, JR., Martin, PR., et al.[2023]

In a study involving five men with chronic apraxia of speech, both intense and traditional Sound Production Treatment (SPT) improved articulation, but the traditional method showed better long-term retention of gains.

The less intense SPT (1 hour per day) led to superior maintenance of accuracy for untreated words compared to the more intense SPT (3 hours per day), suggesting that a distributed approach may be more effective for lasting improvements.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of Treatment Intensity on Outcomes in Acquired Apraxia of Speech. Wambaugh, JL., Wright, S., Boss, E., et al.[2019]

In a study of 13 patients with primary progressive apraxia of speech (PPAOS), significant longitudinal changes in tau pathology were observed using flortaucipir (FTP) PET imaging, indicating its potential to track disease progression in neurodegenerative conditions associated with 4-repeat tau pathology.

The study found that changes in FTP uptake were more pronounced in PPAOS patients compared to cognitively unimpaired controls, particularly in specific brain regions, suggesting that FTP imaging could be a valuable tool for monitoring clinical changes in patients with PPAOS.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Longitudinal flortaucipir ([18F]AV-1451) PET imaging in primary progressive apraxia of speech. Utianski, RL., Martin, PR., Botha, H., et al.[2021]

In a study involving 66 participants (6 C9orf72 expansion carriers, 6 svPPA patients, and 54 healthy controls), 18F-Flortaucipir PET scans showed significantly higher retention in svPPA patients compared to healthy controls, particularly in the lateral temporal cortex.

C9orf72 mutation carriers exhibited limited 18F-Flortaucipir retention, suggesting that increased binding is not a universal characteristic of TDP-43 related diseases, and indicating that the mechanism of action for 18F-Flortaucipir may differ across various TDP-43 pathologies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

18F-Flortaucipir in TDP-43 associated frontotemporal dementia. Smith, R., Santillo, AF., Waldö, ML., et al.[2021]

About 40-50% of patients with progressive apraxia of speech (PAOS) show abnormal dopamine transporter (DaT) scan results, indicating potential changes in dopamine function as the disease progresses.

Despite some patients showing visual abnormalities in their DaT scans, quantitative measures did not correlate with clinical progression of symptoms like parkinsonism, suggesting that DaT scans may not fully reflect the clinical status of PAOS patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Longitudinal changes in dopamine transporter uptake scans in progressive apraxia of speech. Utianski, RL., Trang Thu Pham, N., Botha, H., et al.[2023]

Progressive apraxia of speech is identified as a potential target for disease-modifying therapies aimed at tau pathology, based on a study of 24 patients who underwent serial MRI scans and detailed speech assessments.

The study found that measuring atrophy rates in specific brain regions, like the precentral gyrus and supplementary motor area, requires fewer than 50 subjects per treatment group to effectively detect treatment effects, making it feasible to include progressive apraxia of speech in future clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sample size calculations for clinical trials targeting tauopathies: a new potential disease target. Whitwell, JL., Duffy, JR., Strand, EA., et al.[2018]

In a study of 14 patients with primary progressive apraxia of speech (PPAOS), increased tau tracer uptake was observed in key speech production areas of the brain, such as Broca's area, indicating a potential link between tau pathology and speech disorders.

The study found that patients with PPAOS who also had aphasia showed tau accumulation in Broca's area, while those without aphasia did not, suggesting that the presence of aphasia may be associated with specific patterns of tau deposition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tau-PET imaging with [18F]AV-1451 in primary progressive apraxia of speech. Utianski, RL., Whitwell, JL., Schwarz, CG., et al.[2019]

Flortaucipir PET scans can effectively predict near-term clinical progression in patients with Alzheimer's disease (AD) and mild cognitive impairment (MCI), with 70% of those showing an advanced AD pattern experiencing significant clinical deterioration over 18 months.

The study involved 364 participants, and those with an advanced AD pattern had a higher risk of clinical decline compared to those with a nonadvanced pattern, indicating that these scans can provide valuable prognostic information for patient management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Aggregated Tau Measured by Visual Interpretation of Flortaucipir Positron Emission Tomography and the Associated Risk of Clinical Progression of Mild Cognitive Impairment and Alzheimer Disease: Results From 2 Phase III Clinical Trials. Lu, M., Pontecorvo, MJ., Devous, MD., et al.[2022]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7060829/

Longitudinal Flortaucipir ([18F]AV-1451) PET Imaging in ... Elevated flortaucipir ([ 18 F]AV-1451; FTP) uptake has been observed cross-sectionally in patients with PPAOS and those with aphasia.

2. withpower.com withpower.com/trial/phase-4-frontotemporal-dementia-6-2018-eee2d

AV-1451 Imaging for Apraxia of Speech Research shows that AV-1451 (Flortaucipir F 18) can track disease progression in primary progressive apraxia of speech by highlighting areas in the brain where ...

3. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0010945219303727

Longitudinal flortaucipir ([18F]AV-1451) PET imaging in ... Primary progressive apraxia of speech (PPAOS) is a term used to describe a neurodegenerative condition in which apraxia of speech (AOS), a deficit of speech ...

4. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/31830664/

Longitudinal flortaucipir ([18F]AV-1451) PET imaging in ... Elevated flortaucipir ([ 18 F]AV-1451; FTP) uptake has been observed cross-sectionally in patients with PPAOS and those with aphasia.

5. sciencedirect.com sciencedirect.com/science/article/abs/pii/S001094521730429X

Tau-PET imaging with [18F]AV-1451 in primary ... In a recent longitudinal study, we observed that in some PPAOS patients, the apraxia of speech remained the most salient feature over an average duration of 7 ...

6. synapse.patsnap.com synapse.patsnap.com/article/what-are-the-side-effects-of-flortaucipir-f-18

What are the side effects of Flortaucipir F-18? The most common side effects are minor and include injection site reactions and mild systemic symptoms. Rarely, more severe allergic reactions can occur.

7. medchemexpress.com medchemexpress.com/T807.html?srsltid=AfmBOoqI9MzFc-FmtS_mL95Mghtx5MxwW9dWUJlyfqZ4IohkrGSi0TEh

T807 (AV-1451) | Tau PETTracer Validating novel tau positron emission tomography tracer [F-18]-AV-1451 (T807) on postmortem brain tissue. ... SAFETY DATA SHEET (SDS). English - EN (393 KB) ...

8. go.drugbank.com go.drugbank.com/drugs/DB14914

Flortaucipir F-18: Uses, Interactions, Mechanism of Action The safety and efficacy of flortaucipir F-18 in patients being evaluated for chronic traumatic encephalopathy are unknown and hence is not recommended.

9. clinicaltrials.gov clinicaltrials.gov/ct2/show/NCT01818661

Longitudinal Multi-Modality Imaging in Progressive Apraxia ... The study is designed to determine the relationship between structural and functional changes in the brain on imaging and progression of speech and language, ...