- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT05437159
Investigating Speech Sequencing in Neurotypical Speakers and Persons With Disordered Speech
February 6, 2023 updated by: Frank Guenther, Boston University Charles River Campus
Sequencing and Initiation in Speech Production: Investigating Speech Sequencing in Neurotypical Speakers, Persons Who Stutter, and Persons With Primary Progressive Aphasia
Persistent developmental stuttering affects more than three million people in the United States, and it can have profound adverse effects on quality of life.
Despite its prevalence and negative impact, stuttering has resisted explanation and effective treatment, due in large part to a poor understanding of the neural processing impairments underlying the disorder.
The overall goal of this study is to improve understanding of the brain mechanisms involved in speech motor planning and how these are disrupted in neurogenic speech disorders, like stuttering.
The investigators will do this through an integrated combination of experiments that involve speech production, functional MRI, and non-invasive brain stimulation.
The study is designed to test hypotheses regarding the brain processes involved in learning and initiating new speech sound sequences and how those processes compare in persons with persistent developmental stuttering and those with typical speech development.
These processes will be studied in both adults and children.
Additionally, these processes will be investigated in patients with neurodegenerative speech disorders (primary progressive aphasia) to further inform the investigators understanding of the neural mechanisms that support speech motor sequence learning.
Together these experiments will result in an improved account of the brain mechanisms underlying speech production in fluent speakers and individuals who stutter, thereby paving the way for the development of new therapies and technologies for addressing this disorder.
Study Overview
Status
Not yet recruiting
Intervention / Treatment
- Behavioral: Learning of non-native phoneme combinations: 6 training sessions
- Behavioral: Learning of non-native phoneme combinations: 1 training session
- Device: Anodal tDCS
- Device: Sham tDCS
- Behavioral: Learning of novel multisyllabic nonwords
- Behavioral: Learning of non-native phoneme combinations: 8 training sessions
Study Type
Interventional
Enrollment (Anticipated)
315
Phase
- Not Applicable
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Contact
- Name: Frank H Guenther, PhD
- Phone Number: 6173535765
- Email: guenther@bu.edu
Study Contact Backup
- Name: Barbara Holland
- Phone Number: 6173536181
- Email: splab@bu.edu
Study Locations
-
-
Massachusetts
-
Boston, Massachusetts, United States, 02215
- Boston University
-
Contact:
- Frank H Guenther, PhD
- Phone Number: 617-353-5765
- Email: guenther@bu.edu
-
Contact:
- Barbara Holland, MA
- Phone Number: 617-353-6181
- Email: splab@bu.edu
-
Principal Investigator:
- Frank H Guenther, PhD
-
Sub-Investigator:
- Jason A Tourville, PhD
-
Sub-Investigator:
- Alfonso Nieto-Castonon, PhD
-
Sub-Investigator:
- Tyler K Perrachione, PhD
-
Sub-Investigator:
- Hilary Miller, MS
-
Boston, Massachusetts, United States, 02129
- Massachusetts General Hospital
-
Contact:
- Bradford Dickerson, MD
- Phone Number: 617-726-8689
- Email: brad.dickerson@mgh.harvard.edu
-
Sub-Investigator:
- Bradford Dickerson, MD
-
-
Michigan
-
Ann Arbor, Michigan, United States, 48109
- University of Michigan
-
Contact:
- Soo-Eun Chang, PhD
- Phone Number: 734-232-0300
- Email: sooeunc@med.umich.edu
-
-
Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
6 years and older (ADULT, OLDER_ADULT, CHILD)
Accepts Healthy Volunteers
Yes
Genders Eligible for Study
All
Description
Inclusion Criteria
- Healthy individuals with no history of neurological, speech, or hearing disorders (other than stuttering in studies that involve adults who stutter).
- To maximize the uniformity of prior exposure to the speech stimuli that will be used, only native speakers of American English will be recruited, and only those with limited exposure to a second language will be enrolled.
- All adult participants will also pass a standard pure-tone hearing screening at a 25dB hearing level threshold at 500, 1k, 2k, and 4kHz frequencies.
- All participating children will pass a hearing screening at a 20 dB threshold at 500, 1k, 2k, and 4k Hz.
- Participants in experiments that require them to read orthographic stimuli must have normal or corrected-to-normal vision (MRI-safe corrective glasses are available at the Boston University Cognitive Neuroimaging Center for use during neuroimaging).
- Participating children will complete additional speech, language, hearing, and cognitive tests to ensure that they are within normal performance ranges for their age with the exception of stuttering for children in the children who stutter (CWS) group.
- Persons who stutter will be evaluated formally by a speech-language pathologist to assess stuttering severity and to ensure the absence of other speech or language disorders. PWS will have no history of neurological disorder other than stuttering, and will demonstrate very mild to severe stuttering according to the Stuttering Severity Instrument for Children and Adults - 4th Edition (SSI-4: PRO-ED, Inc.), that is confirmed by clinical reports and expressed concern by the subject and/or guardian.
- Participants with primary progressive aphasia (PPA) will have been diagnosed through the Massachusetts General Hospital Frontotemporal Disorders Unit (MGH-FTD) by an experienced neurologist in coordination with a speech-language pathologist.
- Participants with PPA will have a score of 1.0 or lower on the Clinical Dementia Rating scale (i.e., mild cognitive impairment or mild dementia) to ensure cognitive levels are sufficient to complete the task.
- All participants with PPA must have a recent clinical assessment and T1 structural neuroimaging scan through the MGH-FTD Unit for eligibility for this study.
Exclusion Criteria
- Participants in studies that involve tDCS or MRI scanning will have no contraindications specific to those procedures. For the tDCS study, this includes individuals who have a metallic implant in the head or electrically sensitive devices implanted in the body, a history of seizures, significant scalp lesions, or pregnancy.
- For MRI studies, this includes a history of seizures, severe claustrophobia, the presence of magnetically or mechanically active implant, ferromagnetic material embedded in any part of the body, or pregnancy).
- All participants will perform a standardized nonword repetition pre-test (the Dollaghan and Campbell Nonword Repetition Task) to assess working memory performance. Participants who perform more than 2 standard deviations below the norm for their age range will be deemed to be unable to perform the experimental task and released from further participation.
- Participating children will have no history of neurological disorder other than stuttering, and will demonstrate very mild to severe stuttering according to the Stuttering Severity Instrument for Children and Adults, 4th Edition, that is confirmed by clinical reports and expressed concern by the subject and/or guardian.
- Children under the age of 6 and over the age of 8 will not enrolled in this study.
- Participants with PPA will not be eligible for this study if they are taking any medications that would be expected to affect speech or language.
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: BASIC_SCIENCE
- Allocation: RANDOMIZED
- Interventional Model: PARALLEL
- Masking: NONE
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
EXPERIMENTAL: Sub-syllabic learning and fMRI
60 adults with neurotypical speech development will participate in this arm.
Subjects will learn novel 1-syllable nonsense words formed by non-native phoneme combinations during 6 training sessions over 2 days.
Following training, subjects will participate in a functional magnetic resonance imaging (fMRI) session on a third day to measure brain activity associated with producing the words learned during training and with a set of unfamiliar words also formed by non-native phoneme combinations.
|
Each trial of the training sessions will follow a simple reaction time protocol in which a nonsense syllable containing novel consonant clusters (e.g., GDADK) is produced as quickly and accurately as possible after an auditory prompt presented via earphones.
During each training session, the participant will practice producing a set of 8 stimuli (the Fully Learned stimuli).
Each of the 8 Fully Learned stimuli will be produced 60 times over the 6 training sessions.
|
EXPERIMENTAL: Sub-syllabic learning and anodal tDCS of inferior frontal sulcus
35 adults with neurotypical speech development will participate in this arm.
Subjects will learn novel 1-syllable nonsense words formed by non-native phoneme combinations.
During the training, anodal transcranial direct current stimulation (tDCS) will be applied to the the subject's left inferior frontal sulcus.
|
Each trial of the training sessions will follow a simple reaction time protocol in which a nonsense syllable containing novel consonant clusters (e.g., GDADK) is produced as quickly and accurately as possible after an auditory prompt presented via earphones.
During the training session, the participant will practice producing a set of 3 stimuli (the Fully Learned stimuli).
Each of the 3 Fully Learned stimuli will be produced 60 times.
Continuous anodal tDCS is delivered to a speech processing area of the brain during a 19-minute speech training session.
The tDCS stimulation will ramp up to its maximum value (2 milliamperes) in the minute prior to the training session and maintained at that level throughout the session.
|
EXPERIMENTAL: Sub-syllabic learning and anodal tDCS of cerebellum
35 adults with neurotypical speech development will participate in this arm.
Subjects will learn novel 1-syllable words formed by non-native phoneme combinations.
During the training, continuous anodal transcranial direct current stimulation (tDCS) will be applied to the the subject's right cerebellum.
|
Each trial of the training sessions will follow a simple reaction time protocol in which a nonsense syllable containing novel consonant clusters (e.g., GDADK) is produced as quickly and accurately as possible after an auditory prompt presented via earphones.
During the training session, the participant will practice producing a set of 3 stimuli (the Fully Learned stimuli).
Each of the 3 Fully Learned stimuli will be produced 60 times.
Continuous anodal tDCS is delivered to a speech processing area of the brain during a 19-minute speech training session.
The tDCS stimulation will ramp up to its maximum value (2 milliamperes) in the minute prior to the training session and maintained at that level throughout the session.
|
SHAM_COMPARATOR: Sub-syllabic learning and sham tDCS
35 adults with neurotypical speech development will participate in this arm.
Subjects will learn novel 1-syllable words formed by non-native phoneme combinations.
During training, Sham transcranial direct current stimulation stimulation (tDCS) will be delivered to the subject's brain.
|
Each trial of the training sessions will follow a simple reaction time protocol in which a nonsense syllable containing novel consonant clusters (e.g., GDADK) is produced as quickly and accurately as possible after an auditory prompt presented via earphones.
During the training session, the participant will practice producing a set of 3 stimuli (the Fully Learned stimuli).
Each of the 3 Fully Learned stimuli will be produced 60 times.
Sham tDCS stimulation is delivered to a speech processing area of the brain during a 19-minute speech training session.
During the minute prior to training onset, the tDCS stimulator is ramped up to 2 milliamperes and then back down to 0.
|
EXPERIMENTAL: Multisyllabic learning and fMRI in adults
30 adults persistent developmental stuttering (AWS) and 30 adults with neurotypical speech development (ANS) will participate in this arm.
Subjects will learn nonsense words formed by novel combinations of 3 syllables that are legal in American English during 6 training sessions over 2 days.
Following training, subjects will participate in a functional magnetic resonance imaging (fMRI) session on a third day to measure brain activity associated with producing the words formed by pairing 2 learned 3-syllable strings learned during training and those formed by pairing 2 unfamiliar 3-syllable strings.
Behavioral measures extracted from the data will be used to compare performance before and after training and across the AWS and ANS participants.
|
Each trial of the training sessions (total of 6 training sessions over 2 days) will follow a simple reaction time protocol in which a nonword stimulus formed by 2 or 3 syllables that are legal in American English is presented auditorily to the participant, who then produces the stimulus as quickly and accurately as possible.
During training, each participant will repeatedly produce 6 nonwords, with each nonword produced a total of 60 times over the 6 training sessions.
|
EXPERIMENTAL: Multisyllabic learning in children
45 children with persistent developmental stuttering (CWS) and 45 children with neurotypical speech development (CNS) will participate in this arm.
Subjects will learn nonsense words formed by novel combinations of 2 syllables that are legal in American English during 6 training sessions over 2 days.
Behavioral measures extracted from the data will be used to compare performance before and after training and across the CWS and CNS participants.
|
Each trial of the training sessions (total of 6 training sessions over 2 days) will follow a simple reaction time protocol in which a nonword stimulus formed by 2 or 3 syllables that are legal in American English is presented auditorily to the participant, who then produces the stimulus as quickly and accurately as possible.
During training, each participant will repeatedly produce 6 nonwords, with each nonword produced a total of 60 times over the 6 training sessions.
|
EXPERIMENTAL: Sub-syllabic learning in PPA
30 adults with primary progressive aphasia (PPA) will participate in this arm.
Subjects will learn novel 1-syllable nonsense words formed by non-native phoneme combinations during 8 training sessions over 2 days.
Following training, subjects will complete a behavioral test to compare their performance on the words learned during training with a set of unfamiliar words also formed by non-native phoneme combinations.
|
Each trial of the training sessions will follow a simple reaction time protocol in which a nonsense syllable containing novel consonant clusters (e.g., GDADK) is produced as quickly and accurately as possible after an auditory prompt presented via earphones.
During each training session, the participant will practice producing a set of 3 stimuli (the Fully Learned stimuli).
Each of the 3 Fully Learned stimuli will be produced 120 times over the 8 training sessions.
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Change from baseline in production error rate
Time Frame: Evaluated at Baseline and immediately following intervention
|
Investigators will compare mean error rates when producing newly learned speech sequences versus novel speech sequences of the same length in each arm.
This measure will be used to test hypotheses regarding speech motor learning and brain activity and how these compare in persons with persistent developmental stuttering and persons with neurotypical speech.
|
Evaluated at Baseline and immediately following intervention
|
Change from baseline in utterance duration
Time Frame: Evaluated at Baseline and immediately following intervention
|
Investigators will measure changes in utterance duration before and after speech sequence training to test hypotheses concerning differences in the neural mechanisms responsible for speed/duration improvements compared to improvements in accuracy (i.e., reductions in error rate).
|
Evaluated at Baseline and immediately following intervention
|
Change from baseline in reaction time
Time Frame: Evaluated at Baseline and immediately following intervention
|
Investigators will measure the time interval between the prompt to begin speech and the subject's speech onset.
Mean reaction time will be compared for learned and novel nonwords in persons with persistent developmental stuttering and persons with neurotypical speech.
|
Evaluated at Baseline and immediately following intervention
|
Percentage of words stuttered
Time Frame: Evaluated at Baseline and immediately following intervention
|
Investigators will compare the percentage of words stuttered under different experimental conditions.
This measure will be used to test hypotheses regarding the effect of speech motor learning on stuttering rate and the relationship between stuttering rate and brain activity.
|
Evaluated at Baseline and immediately following intervention
|
Brain activity measured with functional magnetic resonance imaging
Time Frame: Evaluated at Baseline and immediately following intervention
|
Investigators will measure blood oxygen level dependent (BOLD) brain activity when producing speech utterances in different experimental conditions in adults with persistent developmental stuttering and those with neurotypical speech.
|
Evaluated at Baseline and immediately following intervention
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Cortical white matter connectivity
Time Frame: Evaluated during the MRI scanning procedure
|
Diffusion-weighted MRI will be collected and used to identify relationships between white matter connectivity and behavioral measures.
|
Evaluated during the MRI scanning procedure
|
Cortical morphometry
Time Frame: Evaluated during the MRI scanning procedure
|
Structural MRI will be collected and used to identify relationships between cortical morphometry and behavioral measures.
|
Evaluated during the MRI scanning procedure
|
Working memory test scores
Time Frame: Evaluated at Baseline
|
The Comprehensive Test of Phonological Processing (CTOPP) Second Edition working memory subtest scores for each participant will be used to identify correlations between working memory capacity, task performance, and brain measures in all studies.
|
Evaluated at Baseline
|
Forward digit span
Time Frame: Evaluated at Baseline
|
Scores from the Forward Digit Span task from the Uniform Data Set neuropsychological test battery will be used for each participant with PPA to identify correlations between phonological working memory and task performance.
|
Evaluated at Baseline
|
Stuttering Severity
Time Frame: Evaluated at Baseline
|
The Stuttering Severity Instrument, 4th Edition, will be administered to persons show stutter to identify correlations between stuttering severity and task performance and functional and structural brain measures.
|
Evaluated at Baseline
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Collaborators
Investigators
- Principal Investigator: Frank H Guenther, PhD, Boston University
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (ANTICIPATED)
March 1, 2023
Primary Completion (ANTICIPATED)
May 1, 2026
Study Completion (ANTICIPATED)
May 1, 2026
Study Registration Dates
First Submitted
June 1, 2022
First Submitted That Met QC Criteria
June 27, 2022
First Posted (ACTUAL)
June 29, 2022
Study Record Updates
Last Update Posted (ACTUAL)
February 8, 2023
Last Update Submitted That Met QC Criteria
February 6, 2023
Last Verified
February 1, 2023
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Mental Disorders
- Metabolic Diseases
- Brain Diseases
- Central Nervous System Diseases
- Nervous System Diseases
- Neurologic Manifestations
- Neurobehavioral Manifestations
- Neurocognitive Disorders
- Neurodegenerative Diseases
- TDP-43 Proteinopathies
- Proteostasis Deficiencies
- Dementia
- Language Disorders
- Communication Disorders
- Speech Disorders
- Frontotemporal Lobar Degeneration
- Aphasia
- Frontotemporal Dementia
- Aphasia, Primary Progressive
- Pick Disease of the Brain
- Stuttering
Other Study ID Numbers
- R01DC007683 (NIH)
- 2R01DC007683-16A1 (NIH)
- 1F31DC020352-01A1 (NIH)
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
No
Studies a U.S. FDA-regulated device product
No
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Aphasia, Primary Progressive
-
Massachusetts General HospitalCompletedLogopenic Variant Primary Progressive Aphasia | Non-Fluent Primary Progressive AphasiaUnited States
-
University of Texas at AustinUniversity of California, San Francisco; National Institute on Deafness and...Active, not recruitingPrimary Progressive Aphasia | Aphasia | Semantic Dementia | Logopenic Progressive Aphasia | Semantic Memory Disorder | Nonfluent Aphasia, Progressive | Aphasia, ProgressiveUnited States
-
Johns Hopkins UniversityNational Institute on Aging (NIA)RecruitingPrimary Progressive Aphasia | Logopenic Progressive Aphasia | Non-Fluent Primary Progressive AphasiaUnited States, Canada
-
Mayo ClinicNational Institute on Deafness and Other Communication Disorders (NIDCD)RecruitingPrimary Progressive Aphasia | Apraxia of Speech | PPA | Non-fluent Aphasia | Primary Progressive Non-fluent AphasiaUnited States
-
Massachusetts General HospitalNational Institute on Deafness and Other Communication Disorders (NIDCD)RecruitingLogopenic Variant Primary Progressive Aphasia | Non-fluent Variant Primary Progressive Aphasia | Semantic Variant Primary Progressive AphasiaUnited States
-
Mayo ClinicCompletedPrimary Progressive Aphasia | Aphasia | Semantic Dementia | Apraxia of Speech | Primary Progressive Nonfluent Aphasia | PPA | Non-fluent Aphasia | Progressive AphasiaUnited States
-
University of British ColumbiaTerminatedPrimary Progressive Nonfluent AphasiaCanada
-
Axon Neuroscience SEUnknownPrimary Progressive Nonfluent AphasiaGermany
-
Montreal Heart InstituteActive, not recruitingNeurodegenerative Diseases | Primary Progressive Aphasia | Semantic Dementia | Logopenic Progressive Aphasia | Non-fluent AphasiaCanada
-
Mayo ClinicRecruitingPrimary Progressive Aphasia | Apraxia of Speech | Primary Progressive Nonfluent Aphasia | Non-fluent AphasiaUnited States
Clinical Trials on Learning of non-native phoneme combinations: 6 training sessions
-
University of California, San DiegoActive, not recruitingDepression | Anxiety Disorders and SymptomsUnited States
-
Memorial Sloan Kettering Cancer CenterAckerman Institute for FamilyActive, not recruitingSupport of the Family as a Caregiving SystemUnited States
-
Jonsson Comprehensive Cancer CenterCity of Hope National Medical CenterRecruitingMelanoma | Breast Cancer | Neuroendocrine Tumors | Lung Adenocarcinoma | Metastatic Melanoma | Head and Neck Squamous Cell Carcinoma | Thyroid Cancer | Pancreatic Neuroendocrine Tumor | Uveal Melanoma | Paraganglioma | Adrenocortical Carcinoma | Clinical Stage IV Cutaneous Melanoma AJCC v8 | Acral Melanoma | Cutaneous... and other conditionsUnited States