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

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).

Study Overview

• Status: Recruiting
• Conditions: Primary Progressive Aphasia
• Intervention / Treatment: Device: Active tDCS; Behavioral: individualized language training; Device: Placebo tDCS

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).

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

Contacts and Locations

Study Locations

• Italy
  • BS
    • Brescia, BS, Italy, 25125
      • Recruiting
      • Maria Cotelli
      • Contact: Maria Cotelli, PhD; Phone Number: 00390303501457; Email: mcotelli@fatebenefratelli.eu
  • MI
    • Milan, MI, Italy, 20122
      • Recruiting
      • Tiziana Carandini
      • Contact: Tiziana Carandini, MD; Phone Number: 00390255033814; Email: tiziana.carandini@policlinico.mi.it
    • Milan, MI, Italy, 20148
      • Recruiting
      • Francesca Baglio
      • Contact: Francesca Baglio, MD; Phone Number: 00390240308069; Email: fbaglio@dongnocchi.it
  • PV
    • Pavia, PV, Italy, 27100
      • Recruiting
      • Stefano F. Cappa
      • Contact: Stefano Cappa, MD; Phone Number: 00390382380351; Email: stefano.cappa@mondino.it

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Active tDCS plus individualized language training; The group will receive five consecutive days a week for two weeks of 25 minutes sessions of Active tDCS combined with an individualized language training	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
Active Comparator: Placebo tDCS plus individualized language training; The group will receive five consecutive days a week for two weeks of 25 minutes sessions of Placebo tDCS combined with an individualized language training	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);

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in measure of naming as assessed by International Picture Naming Project Task (IPNP)	International Picture Naming Project Task (IPNP): trained (score range: min= 0, max= 32, higher score=better outcome) and untrained object items (score range: min= 0, max= 32, higher score=better outcome); action items (score range: min= 0, max= 60, higher score=better outcome).	Baseline up to 2 weeks and 3 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in measure of quality of life as assessed by Stroke and Aphasia Quality of Life Scale - 39 (SAQoL-39)	Stroke and Aphasia Quality of Life Scale - 39 (SAQoL-39) is a measure of health-related quality of life in people with long-term aphasia. It provides a total score from 1 to 5 (higher score=better outcome) and it analyzes the following four domains: physical (score range: min= 1, max= 5, higher score=better outcome); psychosocial (score range: min= 1, max= 5, higher score=better outcome); communication (score range: min= 1, max= 5, higher score=better outcome) and energy (score range: min= 1, max= 5, higher score=better outcome).	Baseline up to 2 weeks and 3 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).	Baseline up to 2 weeks and 3 months
Change in measure of quality of life as assessed by Functional Outcome Questionnaire-aphasia	Functional Outcome Questionnaire-aphasia is a measure of aphasia's functional and pragmatic communication in home and community settings, It provides a total score from 32 to 160 (higher score=better outcome) and it is divided into four subscales: communicating basic needs (CBN score range: min= 1, max= 35, higher score=better outcome); making routine requests (MRR score range: min= 1, max= 35, higher score=better outcome); communicating new information (CNI score range: min= 1, max= 40, higher score=better outcome) and attention/other communication skills (AO score range: min= 1, max= 50, higher score=better outcome).	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	Frontotemporal Dementia- Clinical Dementia Rating Scale (FTD-CDR)- Sum of Boxes (score range: min= 0, max= 24, higher score=worse outcome).	Baseline up to 2 weeks and 3 months
Change in dementia severity as assessed by Global Clinical Dementia Rating (CDR) plus NACC FTLD	Global Clinical Dementia Rating (CDR) plus NACC FTLD (score range: min= 0, max= 3, higher score=worse outcome).	Baseline up to 2 weeks and 3 months
Change in aphasia severity as assessed by Progressive Aphasia Severity Scale (PASS)	PASS is a measure of severity and progression of language deficits in patients with PPA. The scale assesses ten linguistic domains (each score range: min= 0, max= 3): articulation (higher score=worse outcome), fluency (higher score=worse outcome), syntax and grammar (higher score=worse outcome), word retrieval and expression (higher score=worse outcome), repetition (higher score=worse outcome), auditory comprehension (higher score=worse outcome), single word comprehension (higher score=worse outcome), reading (higher score=worse outcome), writing (higher score=worse outcome) and functional communication (higher score=worse outcome). Moreover, it analyzes three supplemental domains (each score range: min= 0, max= 3): initiation of conversation (higher score=worse outcome), turn taking during conversation (higher score=worse outcome) and generation of language (higher score=worse outcome).	Baseline up to 2 weeks and 3 months
Change in functional communication skills as assessed by Lincoln Speech Questionnaire	Lincoln Speech Questionnaire provides a speech score (score range: min= 0, max= 14, higher score=better outcome) and an understanding score (score range: min= 0, max= 5, higher score=better outcome).	Baseline up to 2 weeks and 3 months
Change in aphasia severity as assessed by Communication Severity Rating Scale (Goodglass and Kaplan)	Communication Severity Rating Scale (Goodglass and Kaplan): score range: min= 0, max= 5, higher score=better outcome.	Baseline up to 2 weeks and 3 months
Change in depressive symptoms as assessed by Beck Depression Inventory (BDI)	Beck Depression Inventory (BDI): score range: min= 0, max= 63, higher score=worse outcome	Baseline up to 2 weeks and 3 months
Change in behavior and personality as assessed by Frontal Behavioral Inventory (FBI)	Frontal Behavioral Inventory (FBI): score range: min= 0, max= 72, higher score=worse outcome.	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)	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).	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)	Auditory sentence comprehension subtest from Screening for Aphasia in NeuroDegeneration (SAND): total score range: min= 0, max= 8, higher score=better outcome.	Baseline up to 2 weeks and 3 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).	Baseline up to 2 weeks and 3 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).	Baseline up to 2 weeks and 3 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).	Baseline up to 2 weeks and 3 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).	Baseline up to 2 weeks and 3 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).	Baseline up to 2 weeks and 3 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.	Baseline up to 2 weeks and 3 months
Change in measure of oral production as assessed by Picture description subtest from Screening for Aphasia in NeuroDegeneration (SAND)	Picture description subtest from SAND provides Information Units score (score range: min= 0, max= 8, 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 (score range: min= 0, max= 1, higher score=better outcome), number of sentences score (score range: min= 0, max= no limits, higher score=better outcome), number of subordinates/number of sentences score (score range: min= 0, max= no limits, higher score=better outcome), number of repaired sequences/number of words score (score range: min= 0, max= 1, higher score=worse outcome), number of phonological errors/number of words (score range: min= 0, max= 1, higher score=worse outcome), number of lexico-semantic errors/number of words (score range: min= 0, max= 1, higher score=worse outcome).	Baseline up to 2 weeks and 3 months
Change in measure of naming as assessed by Subtest from Aachener Aphasie Test (AAT)	Naming subtest from Aachener Aphasie Test (AAT): score range: min= 0, max= 120, higher score=better outcome.	Baseline up to 2 weeks and 3 months
Change in measure of object naming as assessed by Subtest from Battery for the Assessment of Aphasic Disorders (BADA)	Subtest from Battery for the Assessment of Aphasic Disorders (BADA): score range: min= 0, max= 30, higher score=better outcome.	Baseline up to 2 weeks and 3 months
Change in measure of fluency abilities as assessed by Verbal Fluency (semantic and phonemic)	Verbal Fluency (semantic and phonemic): score range min= 0, max= no limits, higher score=better outcome.	Baseline up to 2 weeks and 3 months
Change in measure of constructional praxia as assessed by Rey-Osterrieth Complex Figure-Copy	Rey-Osterrieth Complex Figure-Copy: score range min= 0, max= 36, higher score=better outcome.	Baseline up to 2 weeks and 3 months
Change in measure of verbal long-term memory as assessed by Story Recall	Story Recall: score range min= 0, max= 28, higher score=better outcome.	Baseline up to 2 weeks and 3 months
Change in measure of nonverbal long-term memory as assessed by Rey-Osterrieth Complex Figure-Recall	Rey-Osterrieth Complex Figure-Recall: score range min= 0, max= 36, higher score=better outcome.	Baseline up to 2 weeks and 3 months
Change in measure of attentional abilities as assessed by Trial Making Test	Trial Making Test: score range: min= n/a, max= no limits, higher score=worse outcome.	Baseline up to 2 weeks and 3 months
Change in measure of executive abilities as assessed by Stroop Test	Stroop Test: score range: min= n/a, max= no limits, higher score=worse outcome.	Baseline up to 2 weeks and 3 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.	Baseline up to 2 weeks and 3 months
Change in molecular biomarkers as assessed by the size and the concentration of plasma Extracellular vesicles (EVs)	Size and the concentration of plasma EVs	Baseline up to 2 weeks
Change in molecular biomarkers as assessed by Neurofilament light chain (NFL) levels	Neurofilament light chain (NFL) levels	Baseline up to 2 weeks
Change in molecular biomarkers as assessed by Glial Fibrillary Acidic Protein (GFAP) levels	Glial Fibrillary Acidic Protein (GFAP) levels	Baseline up to 2 weeks
Change in molecular biomarkers as assessed by brain-derived neurotrophic factor (BDNF)	Brain-derived neurotrophic factor (BDNF) levels	Baseline up to 2 weeks
Change in molecular biomarkers as assessed by neurogranin levels	Neurogranin levels	Baseline up to 2 weeks
Change in functional connectivity as derived from resting-state functional MRI	Functional connectivity as derived from resting-state functional MRI	Baseline up to 2 weeks
Change in structural connectivity as derived from diffusion-weighted MRI	Structural connectivity as derived from diffusion-weighted MRI	Baseline up to 2 weeks

Collaborators and Investigators

• Sponsor: IRCCS Centro San Giovanni di Dio Fatebenefratelli
• Collaborators: Fondazione Regionale per la Ricerca Biomedica (FRRB); IRCCS Fondazione Istituto Neurologico Nazionale Casimiro Mondino, Pavia; Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan; IRCCS Fondazione Don Carlo Gnocchi - ONLUS, Milan

Study record dates

Study Major Dates

• Study Start (Actual): February 1, 2023
• Primary Completion (Anticipated): January 1, 2026
• Study Completion (Anticipated): February 1, 2026

Study Registration Dates

• First Submitted: January 31, 2023
• First Submitted That Met QC Criteria: February 14, 2023
• First Posted (Actual): February 15, 2023

Study Record Updates

• Last Update Posted (Actual): April 14, 2023
• Last Update Submitted That Met QC Criteria: April 12, 2023
• Last Verified: April 1, 2023

More Information

Terms related to this study

• Keywords: Behavioral and neural effects of tDCS combined with language training; Alzheimer's disease and other dementias
• Additional Relevant MeSH Terms: Mental Disorders; Metabolic Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurologic Manifestations; Neurobehavioral Manifestations; Neurocognitive Disorders; Neurodegenerative Diseases; TDP-43 Proteinopathies; Proteostasis Deficiencies; Dementia; Language Disorders; Communication Disorders; Speech Disorders; Frontotemporal Lobar Degeneration; Aphasia; Frontotemporal Dementia; Aphasia, Primary Progressive; Pick Disease of the Brain
• Other Study ID Numbers: MAINSTREAM ID:3430931

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No