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

Trial Summary

What is the purpose of this trial?

The study is designed to determine the relationship between structural and functional changes in the brain on imaging and progression of speech and language, neurological and neuropsychological features in patients with neurodegenerative apraxia of speech (AOS).

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 data supports the effectiveness of the drug AV-1451 (Flortaucipir F 18) 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 tau proteins build up, which is linked to the condition. This suggests it may be useful in understanding and monitoring the disease. ^{1 2 3 4 5}

Is AV-1451 (Flortaucipir F 18) safe for use in humans?

Flortaucipir F 18 has been used in studies with patients having various conditions, such as primary progressive apraxia of speech and Alzheimer's disease, without specific safety concerns reported in these studies. However, the studies mainly focus on its effectiveness in tracking disease progression rather than detailed safety evaluations. ^{1 2 3 6 7}

How does the treatment AV-1451 imaging differ from other treatments for apraxia of speech?

AV-1451 imaging is unique because it uses a PET scan to detect tau protein buildup in the brain, which is associated with primary progressive apraxia of speech. This approach helps track disease progression and is different from other treatments that may not focus on tau pathology. ^{1 2 6 8 9}

Research Team

Jennifer Whitwell, PhD

Principal Investigator

Mayo Clinic

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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 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]

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]

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]

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]

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]

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]

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]

References

1. Italy pubmed.ncbi.nlm.nih.gov

Longitudinal flortaucipir ([18F]AV-1451) PET imaging in primary progressive apraxia of speech. [2021]

2. Italy pubmed.ncbi.nlm.nih.gov

Tau-PET imaging with [18F]AV-1451 in primary progressive apraxia of speech. [2019]

3. England pubmed.ncbi.nlm.nih.gov

18F-Flortaucipir in TDP-43 associated frontotemporal dementia. [2021]

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

Longitudinal changes in dopamine transporter uptake scans in progressive apraxia of speech. [2023]

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

Effects of Treatment Intensity on Outcomes in Acquired Apraxia of Speech. [2019]

6. England pubmed.ncbi.nlm.nih.gov

Motor functions and adaptive behaviour in children with childhood apraxia of speech. [2015]

7. United States 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. [2022]

8. Netherlands pubmed.ncbi.nlm.nih.gov

Acoustic Analysis and Neuroimaging Correlates of Diadochokinetic Rates in Mild-Moderate Primary Progressive Apraxia of Speech. [2023]

9. Germany pubmed.ncbi.nlm.nih.gov

Sample size calculations for clinical trials targeting tauopathies: a new potential disease target. [2018]