Clinical trial NCT06739967: Speech and Language Interventions for Italian People With PPA
Official title: Speech and Language-Tailored Interventions for People With Primary Progressive Aphasia
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Primary Progressive Aphasia(PPA)
Keywords: Speech and language therapy
online intervention
Frontotemporal dementia
Alzheimer&amp;amp;#39;s disease
PPA
Communication Disorders
Neurodegenerative Diseases
Dementia
Lead sponsor: Istituti Clinici Scientifici Maugeri SpA
Sponsor class: OTHER
First posted: 2024-12-18
Enrollment: 30
Sex: ALL
Minimum age (years): 40
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients with primary progressive aphasia.

Brief 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. 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.

Eligibility criteria: Inclusion Criteria:

* 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.

Exclusion Criteria:

* 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

Primary outcomes:
measure: Change in measure of naming after Lexical Retrieval Training (LRT)
timeFrame: From enrollment to the end of treatment at 5 weeks, 3 Months and 6 Months
measure: Change in number of articulatory and grammatical errors
timeFrame: From enrollment to the end of treatment at 5 weeks, 3 Months and 6 Months
measure: Change in measures of patients and caregivers satisfaction and patients functional communication abilities
timeFrame: From enrollment to the end of treatment at 5 weeks, 3 Months and 6 Months
measure: Change on untrained probes within each clinical variant
timeFrame: From enrollment to the end of treatment at 5 weeks, 3 Months and 6 Months
Secondary outcomes:
measure: Change in measure of oral production as assessed by Picture description subtests
timeFrame: From enrollment to the end of treatment at 5 weeks, 3 Months and 6 Months
measure: Change in measure of quality of life as assessed by Communication Outcome After Stroke (COAST)
timeFrame: From enrollment to the end of treatment at 5 weeks, 3 Months and 6 Months
measure: Change in measure of naming as assessed by Picture Naming subtest from Screening for Aphasia in NeuroDegeneration (SAND)
timeFrame: From enrollment to the end of treatment at 5 weeks, 3 Months and 6 Months
measure: Change in measure of comprehension as assessed by Auditory sentence comprehension subtest from Screening for Aphasia in NeuroDegeneration (SAND)
timeFrame: From enrollment to the end of treatment at 5 weeks, 3 Months and 6 Months
measure: Change in measure of comprehension as assessed by Single-word comprehension subtest from Screening for Aphasia in NeuroDegeneration (SAND)
timeFrame: From enrollment to the end of treatment at 5 weeks, 3 Months and 6 Months
measure: Change in measure of repetition as assessed by Repetition subtest from Screening for Aphasia in NeuroDegeneration (SAND)
timeFrame: From enrollment to the end of treatment at 5 weeks, 3 Months and 6 Months
measure: Change in measure of repetition as assessed by Sentence repetition subtest from Screening for Aphasia in NeuroDegeneration (SAND)
timeFrame: From enrollment to the end of treatment at 5 weeks, 3 Months and 6 Months
measure: Change in measure of reading as assessed by Reading subtest from Screening for Aphasia in NeuroDegeneration (SAND)
timeFrame: From enrollment to the end of treatment at 5 weeks, 3 Months and 6 Months
measure: Change in measure of writing as assessed by Writing subtest from Screening for Aphasia in NeuroDegeneration (SAND)
timeFrame: From enrollment to the end of treatment at 5 weeks, 3 Months and 6 Months
measure: Change in measure of semantics as assessed by Semantic association subtest from Screening for Aphasia in NeuroDegeneration (SAND)
timeFrame: From enrollment to the end of treatment at 5 weeks, 3 Months and 6 Months
measure: Change in measure of naming as assessed by Subtest from CAGI battery
timeFrame: From enrollment to the end of treatment at 5 weeks, 3 Months and 6 Months
measure: Change in measure of comprehension as assessed by Single-word comprehension subtest from CAGI
timeFrame: From enrollment to the end of treatment at 5 weeks, 3 Months and 6 Months
measure: Change in measure of Sentence Production as measured by Northwestern Anagram Test-Italian (Nat-I)
timeFrame: From enrollment to the end of treatment at 5 weeks, 3 Months and 6 Months
measure: Change in measure of comprehension as assessed by Sentence Comprehension Task
timeFrame: From enrollment to the end of treatment at 5 weeks, 3 Months and 6 Months
measure: 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)
timeFrame: From enrollment to the end of treatment at 5 weeks, 3 Months and 6 Months
measure: Change in measure of semantics as assessed by Semantic association Test (SAT)
timeFrame: From enrollment to the end of treatment at 5 weeks, 3 Months and 6 Months
measure: Change in measure of repetition as assessed by Repetition subtest from Esame Neuropsicologico per l'Afasia (ENPA)
timeFrame: From enrollment to the end of treatment at 5 weeks, 3 Months and 6 Months
measure: Change in measure of repetition as assessed by Repetition subtest from Aachener Aphasie Test (AAT)
timeFrame: From enrollment to the end of treatment at 5 weeks, 3 Months and 6 Months
measure: Changes in measures of motor speech as assessed by the Motor Speech Evaluation (MSE)
timeFrame: From enrollment to the end of treatment at 5 weeks, 3 Months and 6 Months
measure: Change in measures of Verbal fluency as measured by Phonemic Fluency Test and Semantic Fluency Test
timeFrame: From enrollment to the end of treatment at 5 weeks, 3 Months and 6 Months
measure: Change in measure of global cognitive impairment as assessed by Mini Mental State Examination (MMSE)
timeFrame: From enrollment to the end of treatment at 5 weeks, 3 Months and 6 Months
measure: Change in dementia severity as assessed by Frontotemporal Dementia- Clinical Dementia Rating Scale (FTD-CDR)- Sum of Boxes
timeFrame: From enrollment to the end of treatment at 5 weeks, 3 Months and 6 Months
measure: Structural MRI scan
timeFrame: At baseline, from enrollment to the end of treatment at 5 weeks
measure: Functional MRI scan
timeFrame: At baseline, from enrollment to the end of treatment at 5 weeks
Other outcomes:
Locations:
city: Bari
country: Italy
facility: Istituti Clinici Scientifici Maugeri IRCCS
city: Milan
country: Italy
facility: IRCCS Ospedale San Raffaele
Study officials:
References:
citation: 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.
citation: Grossman M. Primary progressive aphasia: clinicopathological correlations. Nat Rev Neurol. 2010 Feb;6(2):88-97. doi: 10.1038/nrneurol.2009.216.
citation: 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.
citation: Mesulam 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.
citation: Volkmer 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.
citation: Battista 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.
citation: Gorno-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.