A Multimodal Approach for Clinical Diagnosis and Treatment of Primary Progressive Aphasia, MAINSTREAM ID:3430931

Overview

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).

Interventions

• Device Active tDCS
  Active tDCS (anode will be applied over the left DLPFC with the cathode over the right supraorbital region);
• Behavioral individualized language training
  individualized language training
• Device Placebo tDCS
  Placebo tDCS (the current will be turned off 10 seconds after the beginning and turned on for the last 10 seconds of the stimulation period);

Primary outcome measures

• Change in measure of naming as assessed by International Picture Naming Project Task (IPNP) [Time frame: Baseline up to 2 weeks and 3 months]

Secondary outcome measures (12)

• Change in measure of quality of life as assessed by Stroke and Aphasia Quality of Life Scale - 39 (SAQoL-39) [Time frame: Baseline up to 2 weeks and 3 months]
• Change in measure of quality of life as assessed by Communication Outcome After Stroke (COAST) [Time frame: Baseline up to 2 weeks and 3 months]
• Change in measure of quality of life as assessed by Functional Outcome Questionnaire-aphasia [Time frame: Baseline up to 2 weeks and 3 months]
• Change in dementia severity as assessed by Frontotemporal Dementia- Clinical Dementia Rating Scale (FTD-CDR)- Sum of Boxes [Time frame: Baseline up to 2 weeks and 3 months]
• Change in dementia severity as assessed by Global Clinical Dementia Rating (CDR) plus NACC FTLD [Time frame: Baseline up to 2 weeks and 3 months]
• Change in aphasia severity as assessed by Progressive Aphasia Severity Scale (PASS) [Time frame: Baseline up to 2 weeks and 3 months]
• Change in functional communication skills as assessed by Lincoln Speech Questionnaire [Time frame: Baseline up to 2 weeks and 3 months]
• Change in aphasia severity as assessed by Communication Severity Rating Scale (Goodglass and Kaplan) [Time frame: Baseline up to 2 weeks and 3 months]
• Change in depressive symptoms as assessed by Beck Depression Inventory (BDI) [Time frame: Baseline up to 2 weeks and 3 months]
• Change in behavior and personality as assessed by Frontal Behavioral Inventory (FBI) [Time frame: Baseline up to 2 weeks and 3 months]
• Change in measure of naming as assessed by Picture Naming subtest from Screening for Aphasia in NeuroDegeneration (SAND) [Time frame: Baseline up to 2 weeks and 3 months]
• Change in measure of comprehension as assessed by Auditory sentence comprehension subtest from Screening for Aphasia in NeuroDegeneration (SAND) [Time frame: Baseline up to 2 weeks and 3 months]

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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Triple blind

Primary purpose

Treatment

Study locations

Italy · 4 centers

• Maria Cotelli — Brescia
• Tiziana Carandini — Milan
• Francesca Baglio — Milan
• Stefano F. Cappa — Pavia

Publications

• Cotelli M, Baglio F, Manenti R, Blasi V, Galimberti D, Gobbi E, Pagnoni I, Rossetto F, Rotondo E, Esposito V, De Icco R, Giudice C, Tassorelli C, Catricala E, Perini G, Alaimo C, Campana E, Benussi L, Ghidoni R, Binetti G, Carandini T, Cappa SF. A Multimodal Approach for Clinical Diagnosis and Treatment of Primary Progressive Aphasia (MAINSTREAM): A Study Protocol. Brain Sci. 2023 Jul 12;13(7):106 PMID 37508992

Identifiers

NCT: NCT05730023 · MAINSTREAM ID:3430931

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗