Clinical trial NCT05730023: A Multimodal Approach for Clinical Diagnosis and Treatment of Primary Progressive Aphasia, MAINSTREAM ID:3430931
Official title: A Multimodal Approach for Clinical Diagnosis and Treatment of Primary Progressive Aphasia, MAINSTREAM ID:3430931
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Primary Progressive Aphasia
Keywords: Behavioral and neural effects of tDCS combined with language training
Alzheimer's disease and other dementias
Lead sponsor: IRCCS Centro San Giovanni di Dio Fatebenefratelli
Sponsor class: OTHER
Collaborators: name: Fondazione Regionale per la Ricerca Biomedica
name: Fondazione Mondino
name: Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico
name: IRCCS Fondazione Don Carlo Gnocchi - ONLUS, Milan
First posted: 2023-02-15
Enrollment: 60
Sex: ALL
Minimum age (years): 40
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Primary Progressive Aphasia (PPA) is a syndrome due to different neurodegenerative disorders selectively disrupting language functions. PPA specialist care is underdeveloped. There are very few specialists (neurologists, psychiatrists, neuropsychologists and speech therapists) and few hospitals- or community-based services dedicated to diagnosis and continuing care. Currently, healthcare systems struggle to provide adequate coverage of diagnostic services, and care is too often fragmented, uncoordinated, and unresponsive to the needs of people with PPA and their families. Recently attention has been gained by digital-health technologies, such immunoassay analyzer and high-field MRI, the most promising approaches to increase our understanding of neurodegeneration, and by new non-invasive brain stimulation techniques such as transcranial direct current stimulation (tDCS) that allow a personalized treatment approach. Our goal is to develop a new treatment approach in PPA in which the regional secondary care centers participating in this project should be the hub of a regional network. The MAINSTREAM (WP2- Efficacy of personalized training in the early stage of PPA) looks forward to introduce and evaluate therapeutic innovation such as tDCS coupled with language therapy in rehabilitation settings (WP2 Early Treatment).

This objective will be pursued by conducting a randomized controlled pilot study in order to evaluate the efficacy of a combined treatment of Active (anodal) tDCS and individualized language training compared to Placebo tDCS combined with individualized language training in a subgroup of mild PPA defined using the Progressive Aphasia Severity Scale (PASS) (Sapolsky D, Domoto-Reilly K, Dickerson BCJA. Use of the Progressive Aphasia Severity Scale (PASS) in Monitoring Speech and Language Status in PPA. (2014) 28(8-9):993-1003).

Detailed description: 60 patients with PPA will be recruited from IRCCS Istituto Centro San Giovanni di Dio, Fatebenefratelli, Brescia; IRCCS Fondazione Istituto Neurologico Nazionale C. Mondino, Pavia; Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan and Fondazione Don Carlo Gnocchi - ONLUS, Milan.

The diagnostic evaluation will include cognitive and language testing, neurologic examination and neuroimaging (Magnetic Resonance Imaging (MRI) or Positron Emission Tomography PET)).

All the patients will undergo five consecutive days a week for two weeks of treatment sessions of 25 minutes:

* 30 patients will receive Active tDCS over dorsolateral prefrontal cortex-DLPFC (anode over the left DLPFC with the cathode over the right supraorbital region) while performing an individualized language training;
* 30 patients will receive Placebo tDCS during an individualized language training.

The two groups will be matched for sex, age, education, language severity (as defined in the Frontotemporal Dementia Clinical Dementia Rating subscale), and overall severity according to the FTD Clinical Dementia Rating.

Two trained neuropsychologists will administer the neuropsychological testing at baseline (T0), post-treatment (T1) and 3-months (T2) follow-up. All of assessments will be conducted by the same assessor.

To elucidate the mechanisms underlying tDCS effects, Magnetic Resonance Imaging (MRI) and bimolecular data will be collected at T0 and T1 (after the treatment).

Eligibility criteria: Inclusion Criteria:

* Diagnosis PPA according to the current clinical criteria (Gorno-Tempini et al., 2011);
* Mild PPA defined using the Progressive Aphasia Severity Scale (PASS);
* Italian native speakers.

Exclusion Criteria:

* Presence of developmental disorders;
* Presence of any medical or psychiatric illness that could interfere in completing assessments;
* Presence of any medical condition that represents a contraindication to tDCS.

Primary outcomes:
measure: Change in measure of naming as assessed by International Picture Naming Project Task (IPNP)
timeFrame: Baseline up to 2 weeks and 3 months
Secondary outcomes:
measure: Change in measure of quality of life as assessed by Stroke and Aphasia Quality of Life Scale - 39 (SAQoL-39)
timeFrame: Baseline up to 2 weeks and 3 months
measure: Change in measure of quality of life as assessed by Communication Outcome After Stroke (COAST)
timeFrame: Baseline up to 2 weeks and 3 months
measure: Change in measure of quality of life as assessed by Functional Outcome Questionnaire-aphasia
timeFrame: Baseline up to 2 weeks and 3 months
measure: Change in dementia severity as assessed by Frontotemporal Dementia- Clinical Dementia Rating Scale (FTD-CDR)- Sum of Boxes
timeFrame: Baseline up to 2 weeks and 3 months
measure: Change in dementia severity as assessed by Global Clinical Dementia Rating (CDR) plus NACC FTLD
timeFrame: Baseline up to 2 weeks and 3 months
measure: Change in aphasia severity as assessed by Progressive Aphasia Severity Scale (PASS)
timeFrame: Baseline up to 2 weeks and 3 months
measure: Change in functional communication skills as assessed by Lincoln Speech Questionnaire
timeFrame: Baseline up to 2 weeks and 3 months
measure: Change in aphasia severity as assessed by Communication Severity Rating Scale (Goodglass and Kaplan)
timeFrame: Baseline up to 2 weeks and 3 months
measure: Change in depressive symptoms as assessed by Beck Depression Inventory (BDI)
timeFrame: Baseline up to 2 weeks and 3 months
measure: Change in behavior and personality as assessed by Frontal Behavioral Inventory (FBI)
timeFrame: Baseline up to 2 weeks and 3 months
measure: Change in measure of naming as assessed by Picture Naming subtest from Screening for Aphasia in NeuroDegeneration (SAND)
timeFrame: Baseline up to 2 weeks and 3 months
measure: Change in measure of comprehension as assessed by Auditory sentence comprehension subtest from Screening for Aphasia in NeuroDegeneration (SAND)
timeFrame: Baseline up to 2 weeks and 3 months
measure: Change in measure of comprehension as assessed by Single-word comprehension subtest from Screening for Aphasia in NeuroDegeneration (SAND)
timeFrame: Baseline up to 2 weeks and 3 months
measure: Change in measure of repetition as assessed by Repetition subtest from Screening for Aphasia in NeuroDegeneration (SAND)
timeFrame: Baseline up to 2 weeks and 3 months
measure: Change in measure of repetition as assessed by Sentence repetition subtest from Screening for Aphasia in NeuroDegeneration (SAND)
timeFrame: Baseline up to 2 weeks and 3 months
measure: Change in measure of reading as assessed by Reading subtest from Screening for Aphasia in NeuroDegeneration (SAND)
timeFrame: Baseline up to 2 weeks and 3 months
measure: Change in measure of writing as assessed by Writing subtest from Screening for Aphasia in NeuroDegeneration (SAND)
timeFrame: Baseline up to 2 weeks and 3 months
measure: Change in measure of semantics as assessed by Semantic association subtest from Screening for Aphasia in NeuroDegeneration (SAND)
timeFrame: Baseline up to 2 weeks and 3 months
measure: Change in measure of oral production as assessed by Picture description subtest from Screening for Aphasia in NeuroDegeneration (SAND)
timeFrame: Baseline up to 2 weeks and 3 months
measure: Change in measure of naming as assessed by Subtest from Aachener Aphasie Test (AAT)
timeFrame: Baseline up to 2 weeks and 3 months
measure: Change in measure of object naming as assessed by Subtest from Battery for the Assessment of Aphasic Disorders (BADA)
timeFrame: Baseline up to 2 weeks and 3 months
measure: Change in measure of fluency abilities as assessed by Verbal Fluency (semantic and phonemic)
timeFrame: Baseline up to 2 weeks and 3 months
measure: Change in measure of constructional praxia as assessed by Rey-Osterrieth Complex Figure-Copy
timeFrame: Baseline up to 2 weeks and 3 months
measure: Change in measure of verbal long-term memory as assessed by Story Recall
timeFrame: Baseline up to 2 weeks and 3 months
measure: Change in measure of nonverbal long-term memory as assessed by Rey-Osterrieth Complex Figure-Recall
timeFrame: Baseline up to 2 weeks and 3 months
measure: Change in measure of attentional abilities as assessed by Trial Making Test
timeFrame: Baseline up to 2 weeks and 3 months
measure: Change in measure of executive abilities as assessed by Stroop Test
timeFrame: Baseline up to 2 weeks and 3 months
measure: Change in measure of global cognitive impairment as assessed by Mini Mental State Examination (MMSE)
timeFrame: Baseline up to 2 weeks and 3 months
measure: Change in molecular biomarkers as assessed by the size and the concentration of plasma Extracellular vesicles (EVs)
timeFrame: Baseline up to 2 weeks
measure: Change in molecular biomarkers as assessed by Neurofilament light chain (NFL) levels
timeFrame: Baseline up to 2 weeks
measure: Change in molecular biomarkers as assessed by Glial Fibrillary Acidic Protein (GFAP) levels
timeFrame: Baseline up to 2 weeks
measure: Change in molecular biomarkers as assessed by brain-derived neurotrophic factor (BDNF)
timeFrame: Baseline up to 2 weeks
measure: Change in molecular biomarkers as assessed by neurogranin levels
timeFrame: Baseline up to 2 weeks
measure: Change in functional connectivity as derived from resting-state functional MRI
timeFrame: Baseline up to 2 weeks
measure: Change in structural connectivity as derived from diffusion-weighted MRI
timeFrame: Baseline up to 2 weeks
Other outcomes:
Locations:
city: Brescia
country: Italy
facility: Maria Cotelli
state: BS
city: Milan
country: Italy
facility: Tiziana Carandini
state: MI
city: Milan
country: Italy
facility: Francesca Baglio
state: MI
city: Pavia
country: Italy
facility: Stefano F. Cappa
state: PV
Study officials:
affiliation: IRCCS Istituto Centro San Giovanni di Dio- Fatebenefratelli
name: Maria Cotelli
role: PRINCIPAL_INVESTIGATOR
References: