Treatment for Speech and Language in Primary Progressive Aphasia

Establishing Evidence-based Treatment for Speech and Language in Primary Progressive Aphasia

Primary progressive aphasia (PPA) is a progressive neurological disorder that causes a gradual decline in communication ability as a result of selective neurodegeneration of speech and language networks in the brain. PPA is a devastating condition affecting adults as young as their 40's or 50's, depriving them of the ability to communicate and function in society. There has been significant progress in discovering the neurobiological mechanisms that underlie PPA and in identifying its clinical phenotypes. With these advances, we are poised to investigate behavioral treatments that are grounded in modern cognitive and neuroanatomical concepts. Research documenting the efficacy of speech-language treatment for PPA is emerging, but limited. Systematic research is needed to establish best clinical practices in this unique patient population for whom pharmacological treatment remains elusive. The long-term objectives of this project are to provide evidence-based treatment methods addressing the speech and language deficits in PPA and to determine the neural predictors of responsiveness to intervention. The study has three main goals that build on the findings of our previous work: 1) to examine the utility of treatments designed to facilitate significant, generalized and lasting improvement of speech-language function in PPA, 2) to determine whether treatment alters the trajectory of decline in PPA by comparing performance on primary outcome measures in treated versus untreated participants after a one-year interval, and 3) to identify imaging predictors (gray matter, white matter, and functional connectivity measures) of responsiveness to behavioral intervention in individuals with PPA. In order to accomplish these aims, we will enroll 60 individuals with PPA, who will undergo a comprehensive multidisciplinary evaluation and neuroimaging. Subsequently, participants will be enrolled in treatment designed to promote lasting and generalized improvement of communicative function in core speech-language domains. Participants will be followed for up to one-year post-treatment in order to determine long-term effects of rehabilitation, and their performance will be compared with a historical cohort of untreated PPA patients. This ambitious study and the necessary recruitment will be possible due to an ongoing collaboration with the UCSF Memory and Aging Center, a leading institution in the field of PPA research. The study will broaden the evidence base supporting the efficacy of speech-language intervention in PPA and will provide novel evidence regarding neural predictors of treatment outcomes, with the potential to inform clinical decision-making and improve clinical care for individuals with this debilitating disorder.

Study Overview

• Status: Active, not recruiting
• Conditions: Primary Progressive Aphasia; Aphasia; Semantic Dementia; Logopenic Progressive Aphasia; Semantic Memory Disorder; Nonfluent Aphasia, Progressive; Aphasia, Progressive
• Intervention / Treatment: Behavioral: Lexical Retrieval Training (LRT); Behavioral: Video-Implemented Script Training for Aphasia (VISTA)

• Study Type: Interventional
• Enrollment (Actual): 60
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • California
    • San Francisco, California, United States, 94158
      • University of California San Francisco
  • Texas
    • Austin, Texas, United States, 78712
      • University of Texas

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Meets diagnostic criteria for Primary Progressive Aphasia (PPA; Gorno-Tempini et al., 2011)
• Score of 15 or higher on the Mini-Mental State Examination

Exclusion Criteria:

• Other neurological or psychiatric diagnosis that may contribute to cognitive-linguistic deficits
• Significant, uncorrected visual or hearing impairment that would interfere with participation
• Score of less than 15 on the Mini-Mental State Examination
• Prominent initial non-speech-language impairment (cognitive, behavioral, motoric)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Lexical Retrieval Treatment	Behavioral: Lexical Retrieval Training (LRT); In person or via teletherapy: Participants work on producing spoken and written names of personally relevant target items using a self-cueing hierarchy. Treatment focuses on the use of strategies that capitalize on spared cognitive-linguistic abilities to support word retrieval. The participant completes two (one hour each) sessions per week with a clinician plus daily home practice exercises.
Experimental: Script Training	Behavioral: Video-Implemented Script Training for Aphasia (VISTA); In person or via teletherapy: Participants work on producing personally relevant scripts of 4-6 sentences in length. Length and complexity of scripts are individually tailored. The participant completes 30 minutes per day of home practice, during which they speak in unison with a video/audio model of a healthy speaker clearly articulating the scripts. Biweekly (one hour each) sessions with a clinician target clear and accurate script production, script memorization, and conversational usage of scripts.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in spoken naming of target items	Change in percent correctly named trained/untrained pictures	change from pre-treatment to post-treatment (approximately 8-12 weeks after treatment onset) and follow-ups at 3 months post-treatment, 6 months post-treatment, and 12 months post-treatment
Change in script production accuracy	Change in percent correct intelligible, scripted words for trained/untrained scripts	change from pre-treatment to post-treatment (approximately 6 weeks after treatment onset) and follow-ups at 3 months post-treatment, 6 months post-treatment, and 12 months post-treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change on Western Aphasia Battery, Revised	change on standardized aphasia assessment	change from pre-treatment to post-treatment (approximately 6-12 weeks after treatment onset) and follow-ups at 3 months post-treatment, 6 months post-treatment, and 12 months post-treatment
Change on Boston Naming Test	change on standardized word retrieval assessment	change from pre-treatment to post-treatment (approximately 6-12 weeks after treatment onset) and follow-ups at 3 months post-treatment, 6 months post-treatment, and 12 months post-treatment
Change on Northwestern Assessment of Verbs and Sentences	change on standardized assessment of verb and sentence processing in aphasia	change from pre-treatment to post-treatment (approximately 6-12 weeks after treatment onset) and follow-ups at 3 months post-treatment, 6 months post-treatment, and 12 months post-treatment

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Post-treatment Communication Survey	survey characterizing perceived response to treatment	post-treatment (approximately 6-12 weeks after treatment onset)

Collaborators and Investigators

• Sponsor: University of Texas at Austin
• Collaborators: University of California, San Francisco; National Institute on Deafness and Other Communication Disorders (NIDCD)
• Investigators: Principal Investigator: Maya L Henry, PhD, University of Texas - Austin

Publications and helpful links

General Publications

• Henry ML, Hubbard HI, Grasso SM, Dial HR, Beeson PM, Miller BL, Gorno-Tempini ML. Treatment for Word Retrieval in Semantic and Logopenic Variants of Primary Progressive Aphasia: Immediate and Long-Term Outcomes. J Speech Lang Hear Res. 2019 Aug 15;62(8):2723-2749. doi: 10.1044/2018_JSLHR-L-18-0144. Epub 2019 Aug 7.
• Dial HR, Hinshelwood HA, Grasso SM, Hubbard HI, Gorno-Tempini ML, Henry ML. Investigating the utility of teletherapy in individuals with primary progressive aphasia. Clin Interv Aging. 2019 Feb 25;14:453-471. doi: 10.2147/CIA.S178878. eCollection 2019.
• Henry ML, Hubbard HI, Grasso SM, Mandelli ML, Wilson SM, Sathishkumar MT, Fridriksson J, Daigle W, Boxer AL, Miller BL, Gorno-Tempini ML. Retraining speech production and fluency in non-fluent/agrammatic primary progressive aphasia. Brain. 2018 Jun 1;141(6):1799-1814. doi: 10.1093/brain/awy101.

Helpful Links

• University of Texas Aphasia Research and Treatment Lab
• UCSF Language Neurobiology Lab

Study record dates

Study Major Dates

• Study Start (Actual): July 1, 2017
• Primary Completion (Actual): August 30, 2025
• Study Completion (Estimated): December 30, 2025

Study Registration Dates

• First Submitted: April 30, 2021
• First Submitted That Met QC Criteria: May 5, 2021
• First Posted (Actual): May 11, 2021

Study Record Updates

• Last Update Posted (Estimated): November 13, 2025
• Last Update Submitted That Met QC Criteria: November 11, 2025
• Last Verified: November 1, 2025

More Information

Terms related to this study

• 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; Communication Disorders; Language Disorders; Speech Disorders; Frontotemporal Lobar Degeneration; Pathological Conditions, Signs and Symptoms; Nutritional and Metabolic Diseases; Signs and Symptoms; Aphasia; Frontotemporal Dementia; Aphasia, Primary Progressive; Memory Disorders; Primary Progressive Nonfluent Aphasia
• Other Study ID Numbers: R01DC016291 (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: No
• Studies a U.S. FDA-regulated device product: No