Longitudinal Multi-Modality Imaging in Progressive Apraxia of Speech

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).

Study Overview

• Status: Recruiting
• Conditions: Primary Progressive Aphasia; Apraxia of Speech; PPA; Non-fluent Aphasia; Primary Progressive Non-fluent Aphasia
• Intervention / Treatment: Drug: AV-1451

Detailed Description

Apraxia of Speech (AOS) is a disorder of speech motor planning and/or programming that affects the production of speech, characterized by slow speaking rate, abnormal prosody and distorted sound substitutions, additions, repetitions and prolongations, sometimes accompanied by groping, and trial and error articulatory movements. While AOS is commonly associated with vascular insults, it can be the predominant manifestation of neurodegenerative disease. Apraxia of speech can be the only manifestation of a neurodegenerative disorder. However, AOS very often co-occurs with aphasia, particularly a non-fluent aphasia (NFA) of the Broca's type; a language disorder, typically characterized by agrammatic, telegraphic or truncated spoken language, often accompanied by similar difficulties with written language. Patients with neurodegenerative AOS can have varying degrees of NFA, with the aphasia considered more severe than the AOS in some patients, but with the AOS dominant in others. It is extremely rare to have a patient that presents with NFA that does not also have AOS. Patients with isolated AOS can develop NFA over time, although in some patients the AOS remains isolated for as many as 8-10 years.

Patients with AOS can also develop dysarthria and other non-speech motor symptoms, such as extrapyramidal features, postural instability, extra ocular eye movement abnormalities and limb apraxia. Cognitive impairment can also develop, although is rarely an early feature of the disease. The syndrome is progressive with many patients eventually becoming mute.

Studies have shown that patients with neurodegenerative AOS can be pathologically heterogeneous, with some cases showing deposition of the microtubule associated protein tau, while others have deposition of the TAR DNA binding protein of 43kDa (TDP-43). Typical tau pathologies that are observed include corticobasal degeneration, progressive supranuclear palsy (PSP) and Pick's disease. Clinical features are currently unhelpful in predicting the underlying pathology in these cases, although there is a suggestion that cases with isolated or dominant AOS may be more likely to show tau pathology, particularly PSP.

This project will be the first to assess longitudinal multi-modality neuroimaging in subjects with neurodegenerative AOS. It will allow us to assess all aspects of disease progression in these subjects, including changes on neuroimaging, speech and language, neurological, and neuropsychological assessments, to get a complete picture of dysfunction and progression in these subjects. This project will also be the first to apply DTI and the recently developed technique of resting state fMRI to the study of this disease. These techniques are of great current interest to the field and provide, for the first time, a way of assessing underlying functional and structural connectivity across the brain. Both techniques provide important information about how disease progresses through the brain tissue and have huge potential to be important future biomarkers of many different neurodegenerative diseases.

• Study Type: Interventional
• Enrollment (Estimated): 50
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Sarah Boland, CCRP; Phone Number: 507-284-3863; Email: boland.sarah@mayo.edu

Study Locations

• United States
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Recruiting
      • Mayo Clinic
      • Contact: Sarah Boland, CCRP; Phone Number: 507-284-3863; Email: boland.sarah@mayo.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• We will study subjects that fulfill clinical inclusion criteria for neurodegenerative AOS that have been seen and diagnosed at Mayo Clinic

Exclusion Criteria:

• Subjects with concurrent illnesses that could account for speech and language deficits, such as traumatic brain injury, strokes or developmental syndromes will be excluded.
• Women that are pregnant or post-partum and breast-feeding will be excluded. All women who can become pregnant must have a pregnancy test no more than 48 hours before the PET scan.
• Subjects will also be excluded if MRI is contraindicated (metal in head, cardiac pace maker, e.t.c.), if there is severe claustrophobia, if there are conditions that may confound brain imaging studies (e.g. structural abnormalities, including subdural hematoma or intracranial neoplasm), or if they are medically unstable or are on medications that might affect brain structure or metabolism,(e.g. chemotherapy).
• Subjects will also be excluded if they do not have an informant, or do not consent to research.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Tau positron emission tomography (PET); All subjects will receive Tau PET scan on approximately day 1 or day 2 of study to assess Tau burden in the brain.	Drug: AV-1451; This is used to assess Tau burden in the brain.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
measurement of longitudinal change in neuroimaging and the correlation between change on serial imaging measures and concurrent change on longitudinal measures of clinical performance in neurodegenerative AOS with or without non-fluent aphasia (NFA)	approxiamtely 1-2 years after baseline imaging

Collaborators and Investigators

• Sponsor: Mayo Clinic
• Collaborators: National Institute on Deafness and Other Communication Disorders (NIDCD)
• Investigators: Principal Investigator: Jennifer Whitwell, PhD, Mayo Clinic

Publications and helpful links

Helpful Links

• Mayo Clinic Clinical Trials

Study record dates

Study Major Dates

• Study Start (Actual): July 1, 2018
• Primary Completion (Estimated): June 1, 2028
• Study Completion (Estimated): June 1, 2028

Study Registration Dates

• First Submitted: March 20, 2013
• First Submitted That Met QC Criteria: March 21, 2013
• First Posted (Estimated): March 26, 2013

Study Record Updates

• Last Update Posted (Estimated): November 12, 2025
• Last Update Submitted That Met QC Criteria: November 10, 2025
• Last Verified: November 1, 2025

More Information

Terms related to this study

• Keywords: aphasia; apraxia of speech; non-fluent aphasia
• Additional Relevant MeSH Terms: Neurologic Manifestations; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Mental Disorders; Metabolic Diseases; Neurobehavioral Manifestations; Neurocognitive Disorders; Dementia; Neurodegenerative Diseases; TDP-43 Proteinopathies; Proteostasis Deficiencies; Psychomotor Disorders; Communication Disorders; Language Disorders; Speech Disorders; Frontotemporal Lobar Degeneration; Pathological Conditions, Signs and Symptoms; Nutritional and Metabolic Diseases; Signs and Symptoms; Aphasia; Aphasia, Primary Progressive; Apraxias; Aphasia, Broca; Primary Progressive Nonfluent Aphasia; 7-(6-fluoropyridin-3-yl)-5H-pyrido(4,3-b)indole
• Other Study ID Numbers: 12-008988, 17-010087; R01DC012519-09 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No