Clinical trial NCT04187391: The Effects of a Multimodal Approach for the Treatment of PPA
Official title: The Effects of a Multimodal Approach for the Treatment of Primary Progressive Aphasia
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Primary Progressive Aphasia
Lead sponsor: IRCCS Centro San Giovanni di Dio Fatebenefratelli
Sponsor class: OTHER
Collaborators: name: Asst Degli Spedali Civili Di Brescia
First posted: 2019-12-05
Enrollment: 47
Sex: ALL
Minimum age (years): 40
Maximum age (years): 95
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Change in naming test scores on Picture Naming Task
timeFrame: Baseline up to 2 weeks and 3 months
Secondary outcomes:
measure: Change in quality of life on Stroke and Aphasia Quality of Life
timeFrame: Baseline up to 2 weeks and 3 months
measure: Change in dementia severity on Frontotemporal Dementia-modified Clinical Dementia Rating Scale
timeFrame: Baseline up to 2 weeks and 3 months
measure: Change in cognitive impairment on Mini Mental State Examination
timeFrame: Baseline up to 2 weeks and 3 months
measure: Change in verbal long term memory on Story Recall
timeFrame: Baseline up to 2 weeks and 3 months
measure: Change in nonverbal long term memory on Rey-Osterrieth Complex Figure-Recall
timeFrame: Baseline up to 2 weeks and 3 months
measure: Change in attentional abilities on Trial Making Test
timeFrame: Baseline up to 2 weeks and 3 months
measure: Change in constructional praxia on Rey-Osterrieth Complex Figure-Copy
timeFrame: Baseline up to 2 weeks and 3 months
measure: Change in fluency abilities on Verbal Fluency (semantic and phonemic)
timeFrame: Baseline up to 2 weeks and 3 months
measure: Change in aphasia severity on Screening for Neurodegenerative Aphasia
timeFrame: Baseline up to 2 weeks and 3 months
measure: Change in naming on naming subtest from Aachener Aphasie Test
timeFrame: Baseline up to 2 weeks and 3 months
measure: Change in language impairment on Mini Language State Examination
timeFrame: Baseline up to 2 weeks and 3 months
measure: Change in molecular biomarkers on neurogranin
timeFrame: Baseline up to 2 weeks
measure: Change in imaging biomarkers on fMRI and fNIRS
timeFrame: Baseline up to 2 weeks
Other outcomes:
Locations:
city: Brescia
country: Italy
facility: IRCCS Istituto Centro San Giovanni di Dio Fatebenefratelli
state: BS
Study officials:
affiliation: IRCCS Istituto Centro San Giovanni di Dio- Fatebenefratelli
name: Rosa Manenti, PhD
role: PRINCIPAL_INVESTIGATOR
References: