The Effects of a Multimodal Approach for the Treatment of Primary Progressive Aphasia

Primary Progressive Aphasia Clinical Trial

— ACROSS  

Official title:

The Effects of a Multimodal Approach for the Treatment of Primary Progressive Aphasia

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04187391
• Other study ID #: GR 2018 12365105
• Status: Active, not recruiting
• Phase: N/A
• Start date: January 15, 2020
• Est. completion date: July 4, 2024

Study information

• Verified date: March 2024
• Source: IRCCS Centro San Giovanni di Dio Fatebenefratelli
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Active, not recruiting
• Enrollment: 47
• Est. completion date: July 4, 2024
• Est. primary completion date: June 15, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 40 Years to 95 Years

Eligibility

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.

Related Conditions & MeSH terms

• Aphasia
• Aphasia, Primary Progressive
• Frontotemporal Dementia
• Pick Disease of the Brain
• Primary Progressive Aphasia

Intervention

Device:
• Active tDCS
Active tDCS anode is applied over the left DLPFC with the cathode over the right supraorbital region.
• Placebo tDCS
Placebo tDCS is applied but the current is turned off 10 seconds after the beginning and turned on for the last 10 seconds of the stimulation period.

Behavioral:
• Language training
patients receive language training
• Unstructured cognitive training
patients receive unstructured cognitive training.

Locations

Country	Name	City	State
Italy	IRCCS Istituto Centro San Giovanni di Dio Fatebenefratelli	Brescia	BS

Sponsors (2)

Lead Sponsor	Collaborator
IRCCS Centro San Giovanni di Dio Fatebenefratelli	Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia

Country where clinical trial is conducted

Italy, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in naming test scores on Picture Naming Task	Picture Naming Task: percentage of correct responses (0-100)	Baseline up to 2 weeks and 3 months
Secondary	Change in quality of life on Stroke and Aphasia Quality of Life	Stroke and Aphasia Quality of Life (0-5; higher scores=better quality of life)	Baseline up to 2 weeks and 3 months
Secondary	Change in dementia severity on Frontotemporal Dementia-modified Clinical Dementia Rating Scale	Frontotemporal Dementia-modified Clinical Dementia Rating Scale (0-3; higher scores=greater dementia severity)	Baseline up to 2 weeks and 3 months
Secondary	Change in cognitive impairment on Mini Mental State Examination	Mini Mental State Examination (0-30; higher scores=better cognitive abilities)	Baseline up to 2 weeks and 3 months
Secondary	Change in verbal long term memory on Story Recall	Story Recall (0-28; higher scores=better memory abilities)	Baseline up to 2 weeks and 3 months
Secondary	Change in nonverbal long term memory on Rey-Osterrieth Complex Figure-Recall	Rey-Osterrieth Complex Figure-Recall (0-36; higher scores=better abilities)	Baseline up to 2 weeks and 3 months
Secondary	Change in attentional abilities on Trial Making Test	Trial Making Test (milliseconds; higher scores=worse abilities)	Baseline up to 2 weeks and 3 months
Secondary	Change in constructional praxia on Rey-Osterrieth Complex Figure-Copy	Rey-Osterrieth Complex Figure-Copy (0-36; higher scores=better abilities)	Baseline up to 2 weeks and 3 months
Secondary	Change in fluency abilities on Verbal Fluency (semantic and phonemic)	Verbal Fluency (semantic and phonemic) Test (higher scores=better abilities)	Baseline up to 2 weeks and 3 months
Secondary	Change in aphasia severity on Screening for Neurodegenerative Aphasia	Screening for Neurodegenerative Aphasia Battery (higher scores=better abilities)	Baseline up to 2 weeks and 3 months
Secondary	Change in naming on naming subtest from Aachener Aphasie Test	naming subtest from Aachener Aphasie Test (0-120; higher scores=better abilities)	Baseline up to 2 weeks and 3 months
Secondary	Change in language impairment on Mini Language State Examination	Mini Language State Examination Battery (higher scores=better abilities)	Baseline up to 2 weeks and 3 months
Secondary	Change in molecular biomarkers on neurogranin	neurogranin	Baseline up to 2 weeks
Secondary	Change in imaging biomarkers on fMRI and fNIRS	fMRI and fNIRS	Baseline up to 2 weeks