Working…
COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC: https://www.coronavirus.gov.

Get the latest research information from NIH: https://www.nih.gov/coronavirus.
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04187391
Recruitment Status : Recruiting
First Posted : December 5, 2019
Last Update Posted : January 22, 2020
Sponsor:
Collaborator:
Azienda Ospedaliera Spedali Civili di Brescia
Information provided by (Responsible Party):
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.

Condition or disease Intervention/treatment Phase
Primary Progressive Aphasia Device: Active tDCS Device: Placebo tDCS Behavioral: Language training Behavioral: Unstructured cognitive training Not Applicable

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.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 45 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: The Effects of a Multimodal Approach for the Treatment of Primary Progressive Aphasia
Actual Study Start Date : January 15, 2020
Estimated Primary Completion Date : December 15, 2022
Estimated Study Completion Date : December 15, 2022


Arm Intervention/treatment
Experimental: Active tDCS plus individual language training
Active tDCS plus individual language training
Device: Active tDCS
Active tDCS anode is applied over the left DLPFC with the cathode over the right supraorbital region.

Behavioral: Language training
patients receive language training

Active Comparator: placebo tDCS plus individual language training
placebo tDCS plus individual language training
Device: 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

Active Comparator: Active tDCS plus unstructured cognitive stimulation
Active tDCS plus unstructured cognitive stimulation
Device: Active tDCS
Active tDCS anode is applied over the left DLPFC with the cathode over the right supraorbital region.

Behavioral: Unstructured cognitive training
patients receive unstructured cognitive training.




Primary Outcome Measures :
  1. Change in naming test scores on Picture Naming Task [ Time Frame: Baseline up to 2 weeks and 3 months ]
    Picture Naming Task: percentage of correct responses (0-100)


Secondary Outcome Measures :
  1. Change in quality of life on Stroke and Aphasia Quality of Life [ Time Frame: Baseline up to 2 weeks and 3 months ]
    Stroke and Aphasia Quality of Life (0-5; higher scores=better quality of life)

  2. Change in dementia severity on Frontotemporal Dementia-modified Clinical Dementia Rating Scale [ Time Frame: Baseline up to 2 weeks and 3 months ]
    Frontotemporal Dementia-modified Clinical Dementia Rating Scale (0-3; higher scores=greater dementia severity)

  3. Change in cognitive impairment on Mini Mental State Examination [ Time Frame: Baseline up to 2 weeks and 3 months ]
    Mini Mental State Examination (0-30; higher scores=better cognitive abilities)

  4. Change in verbal long term memory on Story Recall [ Time Frame: Baseline up to 2 weeks and 3 months ]
    Story Recall (0-28; higher scores=better memory abilities)

  5. Change in nonverbal long term memory on Rey-Osterrieth Complex Figure-Recall [ Time Frame: Baseline up to 2 weeks and 3 months ]
    Rey-Osterrieth Complex Figure-Recall (0-36; higher scores=better abilities)

  6. Change in attentional abilities on Trial Making Test [ Time Frame: Baseline up to 2 weeks and 3 months ]
    Trial Making Test (milliseconds; higher scores=worse abilities)

  7. Change in constructional praxia on Rey-Osterrieth Complex Figure-Copy [ Time Frame: Baseline up to 2 weeks and 3 months ]
    Rey-Osterrieth Complex Figure-Copy (0-36; higher scores=better abilities)

  8. Change in fluency abilities on Verbal Fluency (semantic and phonemic) [ Time Frame: Baseline up to 2 weeks and 3 months ]
    Verbal Fluency (semantic and phonemic) Test (higher scores=better abilities)

  9. Change in aphasia severity on Screening for Neurodegenerative Aphasia [ Time Frame: Baseline up to 2 weeks and 3 months ]
    Screening for Neurodegenerative Aphasia Battery (higher scores=better abilities)

  10. Change in naming on naming subtest from Aachener Aphasie Test [ Time Frame: Baseline up to 2 weeks and 3 months ]
    naming subtest from Aachener Aphasie Test (0-120; higher scores=better abilities)

  11. Change in language impairment on Mini Language State Examination [ Time Frame: Baseline up to 2 weeks and 3 months ]
    Mini Language State Examination Battery (higher scores=better abilities)

  12. Change in molecular biomarkers on neurogranin [ Time Frame: Baseline up to 2 weeks ]
    neurogranin

  13. Change in imaging biomarkers on fMRI and fNIRS [ Time Frame: Baseline up to 2 weeks ]
    fMRI and fNIRS



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   40 Years to 95 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04187391


Contacts
Layout table for location contacts
Contact: Rosa Manenti, PhD 00390303501457 rmanenti@fatebenefratelli.eu

Locations
Layout table for location information
Italy
IRCCS Istituto Centro San Giovanni di Dio Fatebenefratelli Recruiting
Brescia, BS, Italy, 25125
Contact: Rosa Manenti, PhD    00390303501457    rmanenti@fatebenefratelli.eu   
Sponsors and Collaborators
IRCCS Centro San Giovanni di Dio Fatebenefratelli
Azienda Ospedaliera Spedali Civili di Brescia
Investigators
Layout table for investigator information
Principal Investigator: Rosa Manenti, PhD IRCCS Istituto Centro San Giovanni di Dio Fatebenefratelli

Layout table for additonal information
Responsible Party: IRCCS Centro San Giovanni di Dio Fatebenefratelli
ClinicalTrials.gov Identifier: NCT04187391    
Other Study ID Numbers: GR 2018 12365105
First Posted: December 5, 2019    Key Record Dates
Last Update Posted: January 22, 2020
Last Verified: January 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
Layout table for MeSH terms
Aphasia
Aphasia, Primary Progressive
Pick Disease of the Brain
Frontotemporal Dementia
Speech Disorders
Language Disorders
Communication Disorders
Neurobehavioral Manifestations
Neurologic Manifestations
Nervous System Diseases
Signs and Symptoms
Dementia
Brain Diseases
Central Nervous System Diseases
Neurocognitive Disorders
Mental Disorders
Frontotemporal Lobar Degeneration
TDP-43 Proteinopathies
Neurodegenerative Diseases
Proteostasis Deficiencies
Metabolic Diseases