Longitudinal Multi-Modality Imaging in Progressive Apraxia of Speech

This study is enrolling participants by invitation only.
Information provided by (Responsible Party):
Jennifer Whitwell, Mayo Clinic
ClinicalTrials.gov Identifier:
First received: March 20, 2013
Last updated: April 8, 2014
Last verified: March 2013

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).

Condition Intervention
Non-fluent Aphasia
Apraxia of Speech
Primary Progressive Non-fluent Aphasia
Primary Progressive Aphasia
Drug: FDG Fluorodeoxyglucose 18

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Diagnostic
Official Title: Longitudinal Multi-Modality Imaging in Progressive Apraxia of Speech

Resource links provided by NLM:

Further study details as provided by Mayo Clinic:

Primary Outcome Measures:
  • 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) [ Time Frame: approxiamtely 1-2 years after baseline imaging ] [ Designated as safety issue: No ]

Estimated Enrollment: 30
Study Start Date: March 2013
Estimated Study Completion Date: March 2015
Estimated Primary Completion Date: March 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: FDG positron emission tomography (PET)
All subjects will receive FDG PET diagnosis on approximately day 1 or day 2 of study to assess brain activity.
Drug: FDG Fluorodeoxyglucose 18

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.


Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • We will study subjects that fulfill clinical inclusion criteria for neurodegenerative AOS that have already been recruited as part of a cross-sectional speech and language based dementias study (R01 DC010367, PI Josephs) that began in February 2010.

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.
  • Subjects meeting criteria for another neurodegenerative disease at baseline evaluation 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.
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Please refer to this study by its ClinicalTrials.gov identifier: NCT01818661

United States, Minnesota
Mayo Clinic
Rochester, Minnesota, United States, 55905
Sponsors and Collaborators
Mayo Clinic
Principal Investigator: Jennifer Whitwell, PhD Mayo Clinic
  More Information

Additional Information:
No publications provided

Responsible Party: Jennifer Whitwell, PI, Mayo Clinic
ClinicalTrials.gov Identifier: NCT01818661     History of Changes
Other Study ID Numbers: 12-008988
Study First Received: March 20, 2013
Last Updated: April 8, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Mayo Clinic:
apraxia of speech
non-fluent aphasia

Additional relevant MeSH terms:
Aphasia, Broca
Aphasia, Primary Progressive
Frontotemporal Dementia
Pick Disease of the Brain
Primary Progressive Nonfluent Aphasia
Brain Diseases
Central Nervous System Diseases
Communication Disorders
Delirium, Dementia, Amnestic, Cognitive Disorders
Frontotemporal Lobar Degeneration
Language Disorders
Mental Disorders
Metabolic Diseases
Nervous System Diseases
Neurobehavioral Manifestations
Neurodegenerative Diseases
Neurologic Manifestations
Proteostasis Deficiencies
Psychomotor Disorders
Signs and Symptoms
Speech Disorders
TDP-43 Proteinopathies

ClinicalTrials.gov processed this record on March 26, 2015