Primary Progressive Aphasia(PPA)PPA-rehabNCT06739967
Speech and Language Interventions for Italian People With PPA
An observational study of Primary Progressive Aphasia(PPA), run by Istituti Clinici Scientifici Maugeri SpA at 2 sites in Italy.
Trial summary
Primary progressive aphasia (PPA) is an umbrella term used to refer to several clinical variants that manifest as an insidious deterioration of speech/language skills, usually due to frontotemporal lobar degeneration and/or Alzheimer's disease. Read more about this study
- Who is it for?
- Ages 40 to 85 yearsHealthy volunteers can take part
- Conditions the study is for
- Primary Progressive Aphasia(PPA)
- What is being tested?
- Behavioral Treatment
- Type of treatment
- Lifestyle or therapy programme
- How many people
- 30 participants
- Where
- 2 sitesItaly
- Study dates
- 1 Sep 2024to 28 Feb 2027
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 40 to 85 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Study population: Patients with primary progressive aphasia.
Who may be able to join
- Diagnosis of PPA according to the current clinical criteria (Gorno-Tempini et al., 2011)
- Mild PPA defined using the Progressive Aphasia Severity Scale (PASS)
- Age between 40 and 85 years
- Patients with Italian mother tongue
- Patients with the ability to sign the informed consent
- Patients with the ability to comply with the study procedures
- Patients with stable pharmacological treatment for at least 4 weeks.
Who cannot join
- Mini-Mental State Exam (MMSE) Score <15
- Presence of other neurological or psychiatric diseases, including cerebrovascular disease
- Severe and uncorrected hearing loss or visual disturbances
- Inability to repeat multi-syllable words (4 syllables)
- Concurrent participation in other pharmacological and non-pharmacological experimental studies
Trial locations and contacts
2 sites in 1 country. Contact the study team or a site near you to ask about taking part.
Italy2 sites, 2 recruiting
- Recruiting
Istituti Clinici Scientifici Maugeri IRCCS
Bari, 70124
Petronilla Battista, PhD, +39 0807814331, petronilla.battista@gbhi.org
Christian Lunetta, MD, +39 0250725266, christian.lunetta@icsmaugeri.it
- Recruiting
IRCCS Ospedale San Raffaele
Milan, 20132
Federica Agosta, MD, PhD, +390226433054, agosta.federica@hsr.it
Elisa Canu, PhD, +390226433063, canu.elisa@hsr.it
About this study
Official title: Speech and Language-Tailored Interventions for People With Primary Progressive Aphasia
Primary progressive aphasia (PPA) is an umbrella term used to refer to several clinical variants that manifest as an insidious deterioration of speech/language skills, usually due to frontotemporal lobar degeneration and/or Alzheimer's disease. Consensus criteria have been proposed by an international community regarding the sub-classification of PPA into three variants: (1) semantic variant PPA, characterized by impaired confrontation naming and single-word comprehension; (2) logopenic variant PPA), characterised by word-finding difficulties and sentence repetition deficits; and (3) non-fluent variant, characterised by agrammatism with or without apraxia of speech.
Speech and language therapists (SLTs) play a crucial role in the diagnostic process and in setting a therapeutic path along with monitoring the evolution of the clinical picture. Despite growing evidence supporting the benefits of speech-language intervention, the frequency with which individuals with PPA are referred for speech and language services, is suboptimal likely due to skepticism regarding the value of speech and language therapy in the context of neurodegeneration, the scarcity of SLTs with expertise in the treatment of PPA, the lack of awareness regarding the role of the SLT amongst referrers, and the geographical barriers that impede access to in-person speech and language services. In Italy, patients with PPA are rarely offered treatment options due to a lack of understanding of the disorder on the part of health professionals and erroneous assumptions regarding the utility of treatment in patients facing a worsening prognosis.
The primary aim of this pilot study is to develop tailored speech and language interventions for patients with different variants of PPA by addressing their linguistic and cognitive difficulties. Secondly, to explore the intervention's effect also on untreated tasks and assess the long-term maintenance of the proposed interventions by monitoring patients for up to six months. Finally, in each PPA variant, the investigators aim to investigate which variables among the sociodemographic, clinical, linguistic/cognitive, and brain MRI features at baseline predict successful clinical results, as well as which structural and functional brain changes are associated with speech and language improvements.
Read the detailed description
A total of 30 PPA patients will be recruited, with a clinical and imaging-supported diagnosis of PPA according to the current diagnostic criteria, and MMSE>15. At the study entry (T0), all patients will undergo a clinical interview, a neurological and neuropsychological evaluation, and a speech and language assessment. All these visits will be repeated soon after the intervention (at week 5, W5), at 3 months (M3), and at 6 months (M6) post-intervention. Specifically, measures of patient's and caregivers' satisfaction and patients' functional communication abilities will be collected as primary outcomes. At baseline (T0) and after intervention (W5), all patients recruited at IRCCS San Raffaele and 40% of patients recruited at IRCCS Maugeri Clinical and Scientific Institute will also perform a brain structural and functional MRI. Thirty healthy controls, matched with PPA cases for age and sex, will be also recruited. Only at baseline (T0), all controls will undergo the same visits as the PPA patients, as well as the brain MRI scan. IRCCS Maugeri Clinical and Scientific Institute will be specifically in charge of the development of the SLT protocols, for the online administration of tailored speech and language interventions and for data analysis. IRCCS Ospedale San Raffaele Milano will be specifically in charge of brain structural and functional MRI acquisition, the definition of task-based functional MRI paradigms, and MRI analysis. This unit will also recruit and collect data on the entire sample of healthy controls. Brain structural and functional changes associated with SLT interventions using the most advanced MRI techniques will be investigated. The sociodemographic, clinical, language, speech, and MRI features obtained in patients will be processed through machine learning to develop a computation paradigm that better defines their prediction value for the intervention's efficacy.
- Conditions
- Primary Progressive Aphasia(PPA)
- Being tested
- Behavioral Treatment
- Keywords
- Speech and language therapy, online intervention, Frontotemporal dementia, Alzheimer&amp;#39;s disease, PPA, Communication Disorders, Neurodegenerative Diseases, Dementia
- Medical subject headings
- Aphasia, Primary Progressive, Communication Disorders, Frontotemporal Dementia, Neurodegenerative Diseases, Dementia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Behavioral TreatmentBehavioural
Also called Speech and Language Therapy, SLT
The SLT intervention will be entirely administered online through a web-based platform. While each of the treatments will engage semantics, phonology, and orthography, the protocols will be tailored relative to the characteristics of each PPA variant. Patients with svPPA and lvPPA will undergo a lexical retrieval training (LRT) intervention implemented using a training cascade.
Patients with nfvPPA will undergo Video-implemented Script Training (VISTA), a choral reading approach training accurate production of functional scripts. The method is based on that implemented in American-English individuals with PPA and aims at improving grammar and motor aspects of speech production by taking advantage of repetitive practice and automaticity.
| Study group | Role | What they receive |
|---|---|---|
| Speech and Language Tailored Interventions | Patients will receive three days a week for 5 weeks of 45 minute sessions of a tailored speech and language intervention Receives: Behavioral: Behavioral Treatment |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in measure of naming after Lexical Retrieval Training (LRT)
Number of correct spoken and written naming of trained and untrained items for patients undergoing the LRT treatment (lvPPA/svPPA)
Measured: From enrollment to the end of treatment at 5 weeks, 3 Months and 6 Months
Change in number of articulatory and grammatical errors
The percentage of script words produced correctly for VISTA for trained and untrained scripts.
Measured: From enrollment to the end of treatment at 5 weeks, 3 Months and 6 Months
Change in measures of patients and caregivers satisfaction and patients functional communication abilities
A Likert scale evaluating relevant categories of functional verbal communication skills in daily situations will be used. The score ranges from 0 - 30. High scores are more favorable, meaning that high scores indicate less interference in participation. The summary scores will be converted to IRT theta values (logit scale). On the logit scale, scores range from -3.0 to +3.0 with 0 logits representing the mean for the calibration sample. High scores are preferable.
Measured: From enrollment to the end of treatment at 5 weeks, 3 Months and 6 Months
Change on untrained probes within each clinical variant
Number of untrained items correctly identified
Measured: From enrollment to the end of treatment at 5 weeks, 3 Months and 6 Months
Secondary outcomes (24)
Change in measure of oral production as assessed by Picture description subtests
To examine the informativeness and efficiency of communication from the connected speech sampled with the Nicholas and Brookshire (1993) picture description task and the Screening for Aphasia in Neurodegeneration (SAND) picture task.
Measured: From enrollment to the end of treatment at 5 weeks, 3 Months and 6 Months
Change in measure of quality of life as assessed by Communication Outcome After Stroke (COAST)
Communication Outcome After Stroke (COAST) is a measure of the functional communication in daily activities and of the impact of the quality of life point of view of aphasia patient (COAST total score range: min= 0, max= 80, higher score=better outcome) and their carer (Carer COAST total score range: min= 0, max= 80, higher score=better outcome)
Measured: From enrollment to the end of treatment at 5 weeks, 3 Months and 6 Months
Change in measure of naming as assessed by Picture Naming subtest from Screening for Aphasia in NeuroDegeneration (SAND)
Picture Naming subtest from Screening for Aphasia in NeuroDegeneration (SAND) provides total score (score range: min= 0, max= 14, higher score=better outcome), living score (score range: min= 0, max= 7, higher score=better outcome) and non-living score (score range: min= 0, max= 7, higher score=better outcome).
Measured: From enrollment to the end of treatment at 5 weeks, 3 Months and 6 Months
Change in measure of comprehension as assessed by Auditory sentence comprehension subtest from Screening for Aphasia in NeuroDegeneration (SAND)
Auditory sentence comprehension subtest from Screening for Aphasia in NeuroDegeneration (SAND): total score range: min= 0, max= 8, higher score=better outcome.
Measured: From enrollment to the end of treatment at 5 weeks, 3 Months and 6 Months
Change in measure of comprehension as assessed by Single-word comprehension subtest from Screening for Aphasia in NeuroDegeneration (SAND)
Single-word comprehension subtest from Screening for Aphasia in NeuroDegeneration (SAND) provides total score (score range: min= 0, max= 12, higher score=better outcome), living score (score range: min= 0, max= 6, higher score=better outcome) and non-living score (score range: min= 0, max= 6, higher score=better outcome).
Measured: From enrollment to the end of treatment at 5 weeks, 3 Months and 6 Months
Change in measure of repetition as assessed by Repetition subtest from Screening for Aphasia in NeuroDegeneration (SAND)
Repetition subtest from Screening for Aphasia in NeuroDegeneration (SAND) provides total score (score range: min= 0, max= 10, higher score=better outcome), words score (score range: min= 0, max= 6, higher score=better outcome) and non-words score (score range: min= 0, max= 4, higher score=better outcome).
Measured: From enrollment to the end of treatment at 5 weeks, 3 Months and 6 Months
Change in measure of repetition as assessed by Sentence repetition subtest from Screening for Aphasia in NeuroDegeneration (SAND)
Sentence repetition subtest from Screening for Aphasia in NeuroDegeneration (SAND) provides total score (score range: min= 0, max= 6, higher score=better outcome), predictable sentences score (score range: min= 0, max= 3, higher score=better outcome) and unpredictable sentences score (score range: min= 0, max= 3, higher score=better outcome).
Measured: From enrollment to the end of treatment at 5 weeks, 3 Months and 6 Months
Change in measure of reading as assessed by Reading subtest from Screening for Aphasia in NeuroDegeneration (SAND)
Reading subtest from Screening for Aphasia in NeuroDegeneration (SAND) provides total score (score range: min= 0, max= 16, higher score=better outcome), words score (score range: min= 0, max= 12, higher score=better outcome) and non-words score (score range: min= 0, max= 4, higher score=better outcome).
Measured: From enrollment to the end of treatment at 5 weeks, 3 Months and 6 Months
Change in measure of writing as assessed by Writing subtest from Screening for Aphasia in NeuroDegeneration (SAND)
Writing subtest from Screening for Aphasia in NeuroDegeneration (SAND) provides Information Units score (score range: min= 0, max= 6, higher score=better outcome), total number of words score (score range: min= 0, max= no limits, higher score=better outcome), number of nouns/total number of words score (score range: min= 0, max= 1, higher score=better outcome), number of verbs/total number of words (score range: min= 0, max= 1, higher score=better outcome), number of correct syntactic structures/total number of syntactic structures score (score range: min= 0, max= 1, higher score=better outcome), number of orthographic errors score (score range: min= 0, max= no limits, higher score=worse outcome), number of lexico-semantic errors/number of words score (score range: min= 0, max= 1, higher score=worse outcome).
Measured: From enrollment to the end of treatment at 5 weeks, 3 Months and 6 Months
Change in measure of semantics as assessed by Semantic association subtest from Screening for Aphasia in NeuroDegeneration (SAND)
Semantic association subtest from Screening for Aphasia in NeuroDegeneration (SAND): total score range: min= 0, max= 4, higher score=better outcome.
Measured: From enrollment to the end of treatment at 5 weeks, 3 Months and 6 Months
Change in measure of naming as assessed by Subtest from CAGI battery
Naming subtest from CAGI: score range: min= 0, max= 48, higher score=better outcome.
Measured: From enrollment to the end of treatment at 5 weeks, 3 Months and 6 Months
Change in measure of comprehension as assessed by Single-word comprehension subtest from CAGI
Single-word comprehension subtest from CAGI: score range: min= 0, max= 48, higher score=better outcome.
Measured: From enrollment to the end of treatment at 5 weeks, 3 Months and 6 Months
Change in measure of Sentence Production as measured by Northwestern Anagram Test-Italian (Nat-I)
The NAT-I is a 22-item test: score range: min= 0, max= 22, higher score=better outcome.
Measured: From enrollment to the end of treatment at 5 weeks, 3 Months and 6 Months
Change in measure of comprehension as assessed by Sentence Comprehension Task
Sentence Comprehension Task: total score range: min= 0, max= 48, higher score=better outcome.
Measured: From enrollment to the end of treatment at 5 weeks, 3 Months and 6 Months
Change in in measure of verb and sentence processing as measured by the Italian version of the Northwestern Assessment of Verbs and Sentences (NAVS-I)
NAVS-I encompasses three subtests: Verb Naming Task (VNT), Verb Comprehension Task (VCT), and Argument Structure Production Task (ASPT).
Measured: From enrollment to the end of treatment at 5 weeks, 3 Months and 6 Months
Change in measure of semantics as assessed by Semantic association Test (SAT)
SAT: total score range: min= 0, max= 76, higher score=better outcome.
Measured: From enrollment to the end of treatment at 5 weeks, 3 Months and 6 Months
Change in measure of repetition as assessed by Repetition subtest from Esame Neuropsicologico per l'Afasia (ENPA)
Repetition subtest from ENPA: score range: min= 0, max= 15, higher score=better outcome.
Measured: From enrollment to the end of treatment at 5 weeks, 3 Months and 6 Months
Change in measure of repetition as assessed by Repetition subtest from Aachener Aphasie Test (AAT)
Repetition subtest from AAT: score range: min= 0, max= 150, higher score=better outcome.
Measured: From enrollment to the end of treatment at 5 weeks, 3 Months and 6 Months
Changes in measures of motor speech as assessed by the Motor Speech Evaluation (MSE)
Motor Speech Evaluation (MSE) score range: min= 0, max= 30, higher score=better outcome.
Measured: From enrollment to the end of treatment at 5 weeks, 3 Months and 6 Months
Change in measures of Verbal fluency as measured by Phonemic Fluency Test and Semantic Fluency Test
Phonemic Fluency Test: higher score= better outcome. Semantic Fluency Test: higher score= better outcome.
Measured: From enrollment to the end of treatment at 5 weeks, 3 Months and 6 Months
Change in measure of global cognitive impairment as assessed by Mini Mental State Examination (MMSE)
Mini Mental State Examination (MMSE): score range: min= 0, max= 30, higher score=better outcome.
Measured: From enrollment to the end of treatment at 5 weeks, 3 Months and 6 Months
Change in dementia severity as assessed by Frontotemporal Dementia- Clinical Dementia Rating Scale (FTD-CDR)- Sum of Boxes
Frontotemporal Dementia- Clinical Dementia Rating Scale (FTD-CDR)- Sum of Boxes (score range: min= 0, max= 24, higher score=worse outcome).
Measured: From enrollment to the end of treatment at 5 weeks, 3 Months and 6 Months
Structural MRI scan
Measure of global and regional volumes of interest (such as whole brain and temporal lobes). Tissue health (from structural scan) will be obtained at baseline to investigate neural predictors of treatment outcome.
Measured: At baseline, from enrollment to the end of treatment at 5 weeks
Functional MRI scan
Task-based activation location (from functional MRI scans) will be obtained at baseline to investigate neural predictors of treatment outcome. Connectivity between brain regions measured using diffusion tensor MRI and resting state functional MRI.
Measured: At baseline, from enrollment to the end of treatment at 5 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Dec 2024
- Study start1 Sep 2024
- Primary completion28 Feb 2027 (estimated)
- Study completion28 Feb 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (7)Papers the sponsor has linked to this study.
- Other trials for Primary Progressive Aphasia(PPA)Studies of the same condition, open and under way.
- More trials run by Istituti Clinici Scientifici Maugeri SpAThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 30 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Istituti Clinici Scientifici Maugeri SpA
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06739967
- Sponsor's protocol ID
- 1767/CEL
- Other IDs
- PNRR-MCNT2-2023-12378220
- Acronym
- PPA-rehab
- Status last verified
- Oct 2026
- First submitted
- 6 Dec 2024
- Last updated
- 26 Oct 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: Privacy Concerns: Protecting the confidentiality of participants is a priority. Sharing IPD could risk the exposure of sensitive personal information.
Publications
Tippett DC, Hillis AE, Tsapkini K. Treatment of Primary Progressive Aphasia. Curr Treat Options Neurol. 2015 Aug;17(8):362. doi: 10.1007/s11940-015-0362-5.
PubMed 26062526Grossman M. Primary progressive aphasia: clinicopathological correlations. Nat Rev Neurol. 2010 Feb;6(2):88-97. doi: 10.1038/nrneurol.2009.216.
PubMed 20139998Henry 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.
PubMed 29718131Mesulam MM. Primary progressive aphasia--differentiation from Alzheimer's disease. Ann Neurol. 1987 Oct;22(4):533-4. doi: 10.1002/ana.410220414. No abstract available.
PubMed 3324947Volkmer A, Rogalski E, Henry M, Taylor-Rubin C, Ruggero L, Khayum R, Kindell J, Gorno-Tempini ML, Warren JD, Rohrer JD. Speech and language therapy approaches to managing primary progressive aphasia. Pract Neurol. 2020 Apr;20(2):154-161. doi: 10.1136/practneurol-2018-001921. Epub 2019 Jul 29.
PubMed 31358572Battista P, Piccininni M, Montembeault M, Messina A, Minafra B, Miller BL, Henry ML, Gorno Tempini ML, Grasso SM. Access, referral, service provision and management of individuals with primary progressive aphasia: A survey of speech-language therapists in Italy. Int J Lang Commun Disord. 2023 Jul-Aug;58(4):1046-1060. doi: 10.1111/1460-6984.12843. Epub 2023 Jan 13.
PubMed 36636857Gorno-Tempini ML, Hillis AE, Weintraub S, Kertesz A, Mendez M, Cappa SF, Ogar JM, Rohrer JD, Black S, Boeve BF, Manes F, Dronkers NF, Vandenberghe R, Rascovsky K, Patterson K, Miller BL, Knopman DS, Hodges JR, Mesulam MM, Grossman M. Classification of primary progressive aphasia and its variants. Neurology. 2011 Mar 15;76(11):1006-14. doi: 10.1212/WNL.0b013e31821103e6. Epub 2011 Feb 16.
PubMed 21325651
Study at a glance
From the registry record, last updated by the sponsor on 26 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Speech and Language-Tailored Interventions for People With Primary Progressive Aphasia
- ClinicalTrials.gov ID
- NCT06739967
- Acronym / sponsor ID
- PPA-rehab / 1767/CEL
- Conditions
- Primary Progressive Aphasia(PPA)
- Keywords
- Speech and language therapy, online intervention, Frontotemporal dementia, Alzheimer&amp;#39;s disease, PPA, Communication Disorders, Neurodegenerative Diseases, Dementia
- Study type
- Observational
- Recruitment status
- Recruiting
- Enrolment
- 30 participants (estimated)
- Lead sponsor
- Istituti Clinici Scientifici Maugeri SpAUniversity, hospital or other
- Study start
- 1 Sep 2024 (actual)
- Primary completion
- 28 Feb 2027 (estimated)
- Study completion
- 28 Feb 2027 (estimated)
- First posted
- 18 Dec 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Primary progressive aphasia (PPA) is an umbrella term used to refer to several clinical variants that manifest as an insidious deterioration of speech/language skills, usually due to frontotemporal lobar degeneration and/or Alzheimer's disease. Consensus criteria have been proposed by an international community regarding the sub-classification of PPA into three variants: (1) semantic variant PPA, characterized by impaired confrontation naming and single-word comprehension; (2) logopenic variant PPA), characterised by word-finding difficulties and sentence repetition deficits; and (3) non-fluent variant, characterised by agrammatism with or without apraxia of speech.
Speech and language therapists (SLTs) play a crucial role in the diagnostic process and in setting a therapeutic path along with monitoring the evolution of the clinical picture. Despite growing evidence supporting the benefits of speech-language intervention, the frequency with which individuals with PPA are referred for speech and language services, is suboptimal likely due to skepticism regarding the value of speech and language therapy in the context of neurodegeneration, the scarcity of SLTs with expertise in the treatment of PPA, the lack of awareness regarding the role of the SLT amongst referrers, and the geographical barriers that impede access to in-person speech and language services. In Italy, patients with PPA are rarely offered treatment options due to a lack of understanding of the disorder on the part of health professionals and erroneous assumptions regarding the utility of treatment in patients facing a worsening prognosis.
The primary aim of this pilot study is to develop tailored speech and language interventions for patients with different variants of PPA by addressing their linguistic and cognitive difficulties. Secondly, to explore the intervention's effect also on untreated tasks and assess the long-term maintenance of the proposed interventions by monitoring patients for up to six months. Finally, in each PPA variant, the investigators aim to investigate which variables among the sociodemographic, clinical, linguistic/cognitive, and brain MRI features at baseline predict successful clinical results, as well as which structural and functional brain changes are associated with speech and language improvements.
Detailed description
A total of 30 PPA patients will be recruited, with a clinical and imaging-supported diagnosis of PPA according to the current diagnostic criteria, and MMSE>15. At the study entry (T0), all patients will undergo a clinical interview, a neurological and neuropsychological evaluation, and a speech and language assessment. All these visits will be repeated soon after the intervention (at week 5, W5), at 3 months (M3), and at 6 months (M6) post-intervention. Specifically, measures of patient's and caregivers' satisfaction and patients' functional communication abilities will be collected as primary outcomes. At baseline (T0) and after intervention (W5), all patients recruited at IRCCS San Raffaele and 40% of patients recruited at IRCCS Maugeri Clinical and Scientific Institute will also perform a brain structural and functional MRI. Thirty healthy controls, matched with PPA cases for age and sex, will be also recruited. Only at baseline (T0), all controls will undergo the same visits as the PPA patients, as well as the brain MRI scan. IRCCS Maugeri Clinical and Scientific Institute will be specifically in charge of the development of the SLT protocols, for the online administration of tailored speech and language interventions and for data analysis. IRCCS Ospedale San Raffaele Milano will be specifically in charge of brain structural and functional MRI acquisition, the definition of task-based functional MRI paradigms, and MRI analysis. This unit will also recruit and collect data on the entire sample of healthy controls. Brain structural and functional changes associated with SLT interventions using the most advanced MRI techniques will be investigated. The sociodemographic, clinical, language, speech, and MRI features obtained in patients will be processed through machine learning to develop a computation paradigm that better defines their prediction value for the intervention's efficacy.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Speech and Language Tailored Interventions | – | Behavioral: Behavioral TreatmentPatients will receive three days a week for 5 weeks of 45 minute sessions of a tailored speech and language intervention |
Who may qualify
- Ages
- 40 to 85 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
- Study population
- Patients with primary progressive aphasia.
Key inclusion criteria (7 listed)
- Diagnosis of PPA according to the current clinical criteria (Gorno-Tempini et al., 2011)
- Mild PPA defined using the Progressive Aphasia Severity Scale (PASS)
- Age between 40 and 85 years
- Patients with Italian mother tongue
- Patients with the ability to sign the informed consent
Key exclusion criteria (5 listed)
- Mini-Mental State Exam (MMSE) Score <15
- Presence of other neurological or psychiatric diseases, including cerebrovascular disease
- Severe and uncorrected hearing loss or visual disturbances
- Inability to repeat multi-syllable words (4 syllables)
- Concurrent participation in other pharmacological and non-pharmacological experimental studies
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Behavioral TreatmentAlso: Speech and Language Therapy, SLTThe SLT intervention will be entirely administered online through a web-based platform. While each of the treatments will engage semantics, phonology, and orthography, the protocols will be tailored relative to the characteristics of each PPA variant. Patients with svPPA and lvPPA will undergo a lexical retrieval training (LRT) intervention implemented using a training cascade. Patients with nfvPPA will undergo Video-implemented Script Training (VISTA), a choral reading approach training accurate production of functional scripts. The method is based on that implemented in American-English individuals with PPA and aims at improving grammar and motor aspects of speech production by taking advantage of repetitive practice and automaticity. | Behavioural | Speech and Language Tailored Interventions |
Primary outcome
Change in measure of naming after Lexical Retrieval Training (LRT)
Time frame: From enrollment to the end of treatment at 5 weeks, 3 Months and 6 Months
Number of correct spoken and written naming of trained and untrained items for patients undergoing the LRT treatment (lvPPA/svPPA)
Change in number of articulatory and grammatical errors
Time frame: From enrollment to the end of treatment at 5 weeks, 3 Months and 6 Months
The percentage of script words produced correctly for VISTA for trained and untrained scripts.
Change in measures of patients and caregivers satisfaction and patients functional communication abilities
Time frame: From enrollment to the end of treatment at 5 weeks, 3 Months and 6 Months
A Likert scale evaluating relevant categories of functional verbal communication skills in daily situations will be used. The score ranges from 0 - 30. High scores are more favorable, meaning that high scores indicate less interference in participation. The summary scores will be converted to IRT theta values (logit scale). On the logit scale, scores range from -3.0 to +3.0 with 0 logits representing the mean for the calibration sample. High scores are preferable.
Change on untrained probes within each clinical variant
Time frame: From enrollment to the end of treatment at 5 weeks, 3 Months and 6 Months
Number of untrained items correctly identified
24 secondary outcomes
Change in measure of oral production as assessed by Picture description subtests
Time frame: From enrollment to the end of treatment at 5 weeks, 3 Months and 6 Months
Change in measure of quality of life as assessed by Communication Outcome After Stroke (COAST)
Time frame: From enrollment to the end of treatment at 5 weeks, 3 Months and 6 Months
Change in measure of naming as assessed by Picture Naming subtest from Screening for Aphasia in NeuroDegeneration (SAND)
Time frame: From enrollment to the end of treatment at 5 weeks, 3 Months and 6 Months
Change in measure of comprehension as assessed by Auditory sentence comprehension subtest from Screening for Aphasia in NeuroDegeneration (SAND)
Time frame: From enrollment to the end of treatment at 5 weeks, 3 Months and 6 Months
Change in measure of comprehension as assessed by Single-word comprehension subtest from Screening for Aphasia in NeuroDegeneration (SAND)
Time frame: From enrollment to the end of treatment at 5 weeks, 3 Months and 6 Months
Change in measure of repetition as assessed by Repetition subtest from Screening for Aphasia in NeuroDegeneration (SAND)
Time frame: From enrollment to the end of treatment at 5 weeks, 3 Months and 6 Months
Change in measure of repetition as assessed by Sentence repetition subtest from Screening for Aphasia in NeuroDegeneration (SAND)
Time frame: From enrollment to the end of treatment at 5 weeks, 3 Months and 6 Months
Change in measure of reading as assessed by Reading subtest from Screening for Aphasia in NeuroDegeneration (SAND)
Time frame: From enrollment to the end of treatment at 5 weeks, 3 Months and 6 Months
Change in measure of writing as assessed by Writing subtest from Screening for Aphasia in NeuroDegeneration (SAND)
Time frame: From enrollment to the end of treatment at 5 weeks, 3 Months and 6 Months
Change in measure of semantics as assessed by Semantic association subtest from Screening for Aphasia in NeuroDegeneration (SAND)
Time frame: From enrollment to the end of treatment at 5 weeks, 3 Months and 6 Months
Change in measure of naming as assessed by Subtest from CAGI battery
Time frame: From enrollment to the end of treatment at 5 weeks, 3 Months and 6 Months
Change in measure of comprehension as assessed by Single-word comprehension subtest from CAGI
Time frame: From enrollment to the end of treatment at 5 weeks, 3 Months and 6 Months
Change in measure of Sentence Production as measured by Northwestern Anagram Test-Italian (Nat-I)
Time frame: From enrollment to the end of treatment at 5 weeks, 3 Months and 6 Months
Change in measure of comprehension as assessed by Sentence Comprehension Task
Time frame: From enrollment to the end of treatment at 5 weeks, 3 Months and 6 Months
Change in in measure of verb and sentence processing as measured by the Italian version of the Northwestern Assessment of Verbs and Sentences (NAVS-I)
Time frame: From enrollment to the end of treatment at 5 weeks, 3 Months and 6 Months
Change in measure of semantics as assessed by Semantic association Test (SAT)
Time frame: From enrollment to the end of treatment at 5 weeks, 3 Months and 6 Months
Change in measure of repetition as assessed by Repetition subtest from Esame Neuropsicologico per l'Afasia (ENPA)
Time frame: From enrollment to the end of treatment at 5 weeks, 3 Months and 6 Months
Change in measure of repetition as assessed by Repetition subtest from Aachener Aphasie Test (AAT)
Time frame: From enrollment to the end of treatment at 5 weeks, 3 Months and 6 Months
Changes in measures of motor speech as assessed by the Motor Speech Evaluation (MSE)
Time frame: From enrollment to the end of treatment at 5 weeks, 3 Months and 6 Months
Change in measures of Verbal fluency as measured by Phonemic Fluency Test and Semantic Fluency Test
Time frame: From enrollment to the end of treatment at 5 weeks, 3 Months and 6 Months
Change in measure of global cognitive impairment as assessed by Mini Mental State Examination (MMSE)
Time frame: From enrollment to the end of treatment at 5 weeks, 3 Months and 6 Months
Change in dementia severity as assessed by Frontotemporal Dementia- Clinical Dementia Rating Scale (FTD-CDR)- Sum of Boxes
Time frame: From enrollment to the end of treatment at 5 weeks, 3 Months and 6 Months
Structural MRI scan
Time frame: At baseline, from enrollment to the end of treatment at 5 weeks
Functional MRI scan
Time frame: At baseline, from enrollment to the end of treatment at 5 weeks
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Oct 2026.
- Background: PubMed 26062526Tippett DC, Hillis AE, Tsapkini K. Treatment of Primary Progressive Aphasia. Curr Treat Options Neurol. 2015 Aug;17(8):362. doi: 10.1007/s11940-015-0362-5.
- Background: PubMed 20139998Grossman M. Primary progressive aphasia: clinicopathological correlations. Nat Rev Neurol. 2010 Feb;6(2):88-97. doi: 10.1038/nrneurol.2009.216.
- Background: PubMed 29718131Henry 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.
- Background: PubMed 3324947Mesulam MM. Primary progressive aphasia--differentiation from Alzheimer's disease. Ann Neurol. 1987 Oct;22(4):533-4. doi: 10.1002/ana.410220414. No abstract available.
- Background: PubMed 31358572Volkmer A, Rogalski E, Henry M, Taylor-Rubin C, Ruggero L, Khayum R, Kindell J, Gorno-Tempini ML, Warren JD, Rohrer JD. Speech and language therapy approaches to managing primary progressive aphasia. Pract Neurol. 2020 Apr;20(2):154-161. doi: 10.1136/practneurol-2018-001921. Epub 2019 Jul 29.
- Background: PubMed 36636857Battista P, Piccininni M, Montembeault M, Messina A, Minafra B, Miller BL, Henry ML, Gorno Tempini ML, Grasso SM. Access, referral, service provision and management of individuals with primary progressive aphasia: A survey of speech-language therapists in Italy. Int J Lang Commun Disord. 2023 Jul-Aug;58(4):1046-1060. doi: 10.1111/1460-6984.12843. Epub 2023 Jan 13.
- Background: PubMed 21325651Gorno-Tempini ML, Hillis AE, Weintraub S, Kertesz A, Mendez M, Cappa SF, Ogar JM, Rohrer JD, Black S, Boeve BF, Manes F, Dronkers NF, Vandenberghe R, Rascovsky K, Patterson K, Miller BL, Knopman DS, Hodges JR, Mesulam MM, Grossman M. Classification of primary progressive aphasia and its variants. Neurology. 2011 Mar 15;76(11):1006-14. doi: 10.1212/WNL.0b013e31821103e6. Epub 2011 Feb 16.
- Individual participant dataSharing planned: No. Privacy Concerns: Protecting the confidentiality of participants is a priority. Sharing IPD could risk the exposure of sensitive personal information.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Primary Progressive Aphasia(PPA), run by Istituti Clinici Scientifici Maugeri SpA at 2 sites in Italy.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 26 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Petronilla Battista, PhD (+390807814331, petronilla.battista@gbhi.org), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in measure of naming after Lexical Retrieval Training (LRT) (time frame: From enrollment to the end of treatment at 5 weeks, 3 Months and 6 Months). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT06739967, which also lists 7 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 Oct 2026.