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The Effects of a Multimodal Approach for the Treatment of PPA

Not Applicable
Completed
Conditions
Primary Progressive Aphasia
Interventions
Device: Active tDCS
Device: Placebo tDCS
Behavioral: Unstructured cognitive training
Behavioral: Language training
Registration Number
NCT04187391
Lead Sponsor
IRCCS Centro San Giovanni di Dio Fatebenefratelli
Brief Summary

Primary Progressive Aphasia (PPA) is an untreatable neurodegenerative disorder that disrupts language functions. Available therapies are mainly symptomatic and recently attention has been gained by new techniques that allow for noninvasive brain stimulation such as transcranial direct current stimulation (tDCS). The primary objective of this study is to evaluate whether the application of Active tDCS (anode over the left dorsolateral prefrontal cortex- DLPFC with the cathode over the right supraorbital region) to the scalp during individualized language training, would improve naming abilities in the agrammatic variant of PPA (avPPA) more than use of one methodology alone. The effect of treatment on the clinical symptoms will be related to changes in brain activity (Magnetic Resonance Imaging, MRI and Functional near-infrared spectroscopy fNIRS) and in biological markers, using a multimodal approach. Finally, we will assess the long-term effects of this approach.

Detailed Description

45 patients with avPPA, will be recruited from IRCCS Istituto Centro San Giovanni di Dio Brescia, Italy and ASST Spedali Civili Brescia, Italy .

Inclusion criteria will be a diagnosis avPPA according to the current clinical criteria (Gorno-Tempini et al., 2011) and a FTD Clinical Dementia Rating score \>0.5 and \<2. Exclusion criteria will be the presence of any medical or psychiatric illness that could interfere in completing assessments and the presence of any medical condition that represents a contraindication to tDCS. All the patients will undergo five consecutive days a week for two weeks of treatment sessions:

15 patients will receive Active tDCS over DLPFC while performing a language training; 15 patients will receive placebo tDCS during language training; 15 patients will receive Active tDCS over DLPFC during unstructured cognitive training.

Two trained neuropsychologists will administer the neuropsychological testing in two sessions. At baseline (T0), post-treatment (T1) and 3-months (T2) follow-up assessments were conducted by the same assessor. Blood sample withdrawal at baseline (T0) and after the DLPFC-tDCS intervention (T1) will be assessed.

To elucidate the mechanisms underlying tDCS effects, structural imaging, functional connectivity (fMRI) alterations and concentration changes of hemoglobin (fNIRS) will be collected off-line. Each avPPA patient will undergo an MRI scan at the ASST Spedali Civili Brescia, Italy at T0 and T1 and a fNIRS acquisition at the IRCCS Istituto Centro San Giovanni di Dio Brescia, Italy at T0, T1 and T2.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
47
Inclusion Criteria
  • Diagnosis avPPA according to the current clinical criteria (Gorno-Tempini et al., 2011)
  • FTD Clinical Dementia Rating (FTD-CDR) score >0.5 and <2
Exclusion Criteria
  • 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 & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Active tDCS plus unstructured cognitive stimulationUnstructured cognitive trainingActive tDCS plus unstructured cognitive stimulation
Active tDCS plus individual language trainingLanguage trainingActive tDCS plus individual language training
Active tDCS plus individual language trainingActive tDCSActive tDCS plus individual language training
placebo tDCS plus individual language trainingPlacebo tDCSplacebo tDCS plus individual language training
placebo tDCS plus individual language trainingLanguage trainingplacebo tDCS plus individual language training
Active tDCS plus unstructured cognitive stimulationActive tDCSActive tDCS plus unstructured cognitive stimulation
Primary Outcome Measures
NameTimeMethod
Change in naming test scores on Picture Naming TaskBaseline up to 2 weeks and 3 months

Picture Naming Task: percentage of correct responses (0-100)

Secondary Outcome Measures
NameTimeMethod
Change in quality of life on Stroke and Aphasia Quality of LifeBaseline up to 2 weeks and 3 months

Stroke and Aphasia Quality of Life (0-5; higher scores=better quality of life)

Change in dementia severity on Frontotemporal Dementia-modified Clinical Dementia Rating ScaleBaseline up to 2 weeks and 3 months

Frontotemporal Dementia-modified Clinical Dementia Rating Scale (0-3; higher scores=greater dementia severity)

Change in cognitive impairment on Mini Mental State ExaminationBaseline up to 2 weeks and 3 months

Mini Mental State Examination (0-30; higher scores=better cognitive abilities)

Change in constructional praxia on Rey-Osterrieth Complex Figure-CopyBaseline up to 2 weeks and 3 months

Rey-Osterrieth Complex Figure-Copy (0-36; higher scores=better abilities)

Change in aphasia severity on Screening for Neurodegenerative AphasiaBaseline up to 2 weeks and 3 months

Screening for Neurodegenerative Aphasia Battery (higher scores=better abilities)

Change in naming on naming subtest from Aachener Aphasie TestBaseline up to 2 weeks and 3 months

naming subtest from Aachener Aphasie Test (0-120; higher scores=better abilities)

Change in molecular biomarkers on neurograninBaseline up to 2 weeks

neurogranin

Change in imaging biomarkers on fMRI and fNIRSBaseline up to 2 weeks

fMRI and fNIRS

Change in verbal long term memory on Story RecallBaseline up to 2 weeks and 3 months

Story Recall (0-28; higher scores=better memory abilities)

Change in nonverbal long term memory on Rey-Osterrieth Complex Figure-RecallBaseline up to 2 weeks and 3 months

Rey-Osterrieth Complex Figure-Recall (0-36; higher scores=better abilities)

Change in fluency abilities on Verbal Fluency (semantic and phonemic)Baseline up to 2 weeks and 3 months

Verbal Fluency (semantic and phonemic) Test (higher scores=better abilities)

Change in attentional abilities on Trial Making TestBaseline up to 2 weeks and 3 months

Trial Making Test (milliseconds; higher scores=worse abilities)

Change in language impairment on Mini Language State ExaminationBaseline up to 2 weeks and 3 months

Mini Language State Examination Battery (higher scores=better abilities)

Trial Locations

Locations (1)

IRCCS Istituto Centro San Giovanni di Dio Fatebenefratelli

🇮🇹

Brescia, BS, Italy

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