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HDtDCS in Logopenic Variant PPA: Effects on Language and Neural Mechanisms

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ClinicalTrials.gov Identifier: NCT03805659
Recruitment Status : Not yet recruiting
First Posted : January 16, 2019
Last Update Posted : January 16, 2019
Sponsor:
Information provided by (Responsible Party):
Medical College of Wisconsin

Brief Summary:
This study aims to evaluate the effectiveness of a therapy called High-Definition Transcranial Direct Current Stimulation (HD-tDCS) for the treatment of the language deficits experienced by people with a type of Primary Progressive Aphasia. This study uses a combination of brain imaging, language assessment, language training sessions, and HD-tDCS therapy as well as placebo therapy sessions.

Condition or disease Intervention/treatment Phase
Primary Progressive Aphasia Device: HD-tDCS Device: Sham Not Applicable

Detailed Description:

The logopenic variant of Primary Progressive Aphasia (lvPPA) is an untreatable neurodegenerative disorder that is often referred to as the 'language form' of Alzheimer's Disease (AD). Transcranial Direct Current Stimulation (tDCS) has emerged as a safe and potentially effective tool that appears to enhance language production when delivered during language training. This technology provides a critical opportunity to conduct disease intervention.

In this study, the investigators will test the hypothesis that High-Definition tDCS (HD-tDCS) will improve performance on language tasks by increasing functional connectivity and by regulating abnormal neuronal oscillatory patterns. The rationale for this project is that a determination of the therapeutic efficacy and the associated neural mechanisms of HD-tDCS in lvPPA is likely to offer a scientific framework whereby new stimulation parameters, conditions, and target sites can be deciphered.

This study will test the hypothesis that HD-tDCS will improve performance on language tasks by increasing functional connectivity and by regulating abnormal neuronal oscillatory patterns. The language performance and functional connectivity changes will be determined in a randomized, double-blind, sham-controlled crossover manner, in which a stimulation of up to 2mA in the targeted cortical tissue or sham is administered to 20 lvPPA subjects age 45 years and older. The order of treatments is counterbalanced in a within-subject crossover design. In brief, study participants will receive sham during one treatment period and stimulation during the other treatment period.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 20 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Intervention Model Description: This is a randomized, double-blind, sham-controlled trial in which stimulation or sham will be administered to 20 subjects over the age of 45 years, with the order of treatments counterbalanced in a within-subject crossover design. Stimulation and sham sessions last 20 minutes and occur for 10 days over a 2-week period.
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description:

An unblinded member of the study team will randomize participants to the treatment conditions. Study Group assignment will be based on random number generation (in blocks of 4) followed by the creation of numbered envelopes.

Participants and the study team members involved in language training, tDCS delivery, and assessment of outcomes will be blind to the treatment received.

Primary Purpose: Treatment
Official Title: High-Definition Transcranial Direct Current Stimulation (HD-tDCS) in Logopenic Variant Primary Progressive Aphasia (lvPPA): Effects on Language and Neural Mechanisms
Estimated Study Start Date : June 2019
Estimated Primary Completion Date : May 2021
Estimated Study Completion Date : May 2021


Arm Intervention/treatment
Experimental: HD-tDCS, then Sham
Subjects receive High Dose transcranial Direct Current Stimulation (HD-tDCS) lasting 20 minutes at an electric current intensity of up to 2mA in the left posterior temporo-parietal cortex (TPC). Stimulation sessions are delivered once a day (QD) for a total of 10 sessions over 2 weeks (Monday-Friday). After a washout period of 16 weeks, subjects receive Sham sessions (no electric current) once a day (QD) for a total of 10 sessions over 2 weeks (Monday-Friday).
Device: HD-tDCS
High-Dose transcranial Direct Current Stimulation
Other Name: Soterix MXN-9 High-Definition stimulator

Device: Sham
Sham sessions (no electric current)

Experimental: Sham, then HD-tDCS
Subjects receive Sham sessions (no electric current) once a day (QD) for a total of 10 sessions over 2 weeks (Monday-Friday). After a washout period of 16 weeks, subjects receive High Dose transcranial Direct Current Stimulation (HD-tDCS) lasting 20 minutes at an electric current intensity of up to 2mA in the left posterior temporo-parietal cortex (TPC). Stimulation sessions are delivered once a day (QD) for a total of 10 sessions over 2 weeks (Monday-Friday).
Device: HD-tDCS
High-Dose transcranial Direct Current Stimulation
Other Name: Soterix MXN-9 High-Definition stimulator

Device: Sham
Sham sessions (no electric current)




Primary Outcome Measures :
  1. Language Performance on seven cognitive assessments: Picture Naming, Letter & Category Fluency, Digit Span Test, Phonological Short-term Memory Test, Word and non-word rhyme matching, Spontaneous Speech Sample, and Communicative Effectiveness Index. [ Time Frame: 2 weeks ]
    Language performance changes as assessed at baseline and after tDCS stimulation procedures as measured by the seven assessments listed above. Scores across all tests within the language battery will be combined into one composite measure to facilitate assessment of overall language performance across domains. All seven scores will be normalized to a Z-score by transforming individual raw test scores according to the mean and standard deviation of the scores for all subjects. Then, Z-scores of each test will be averaged to obtain an individual composite language Z-score (McConathey et al., 2017). We will employ age, years of education, gender, and gray matter (GM) volume as time-invariant covariates to obtain residual variables to determine the LG changes due to stimulation. We will model the LG score as a function of these nuisance regressors. This regression will be performed using all the data (i.e., all subjects, all groups, and all times).


Secondary Outcome Measures :
  1. Brain Connectivity as seen on fMRI (functional MRI) [ Time Frame: 2 weeks ]
    Changes in brain functional connectivity as assessed at baseline and after tDCS stimulation as measured on fMRI

  2. Neuronal Frequencies and Synchronizations as seen on rsMEG (resting state MEG) [ Time Frame: 2 weeks ]
    Changes in abnormal patterns of neuronal frequencies and synchronizations as assessed at baseline and after tDCS stimulation procedures as measured on rsMEG. Connectivity between all ROI-pairs (Region of Interest) will be calculated in the theta (4-8 Hz), alpha (8-12 Hz), beta (13-30 Hz), and low-gamma (30-55 Hz) frequency bands using three different metrics: coherence (COH), phase lag index (PLI), and debiased weighted phase lag index (d-wPLI). Mean connection strengths within 3 intra-hemispheric language-specific ROI-groups, and those between all intra-hemispheric ROIs will be computed. We will also compute mean connection strengths between language ROI-groups and all remaining brain ROIs, and those between each hemispheric ROI and all other brain ROIs.



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Ages Eligible for Study:   45 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Diagnosed with language variant Primary Progressive Aphasia (lvPPA) subtype, defined as either clinical lvPPA or imaging-supported lvPPA in accordance with the most recent diagnostic criteria (Mesulam., 2001; Gorno-Tempini et al., 2011).
  • Fluent in English.
  • 45 years of age or older.
  • Structural brain MRI performed within 2 years prior to enrollment.

Exclusion Criteria:

  • Severe cognitive, auditory or visual impairments that would preclude cognitive testing.
  • Presence of major untreated or unstable psychiatric disease.
  • A chronic medical condition that is not treated or is unstable.
  • The presence of cardiac stimulators or pacemakers.
  • Any metal implants in the skull
  • Contraindications to MRI
  • History of seizures
  • History of dyslexia or other developmental learning disabilities.

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): NCT03805659


Contacts
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Contact: Barbara Blaney 414-955-0609 bblaney@mcw.edu
Contact: Rebecca Rehborg 414-955-0667 rrehborg@mcw.edu

Locations
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United States, Wisconsin
The Medical College of Wisconsin Not yet recruiting
Milwaukee, Wisconsin, United States, 53226
Contact: Barbara Blaney    414-955-0609    bblaney@mcw.edu   
Contact: Rebecca Rehborg    414-955-0667    rrehborg@mcw.edu   
Principal Investigator: Elias Granadillo, MD         
Sponsors and Collaborators
Medical College of Wisconsin
Investigators
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Principal Investigator: Elias Granadillo The Medical College of Wisconsin

Publications:

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Responsible Party: Medical College of Wisconsin
ClinicalTrials.gov Identifier: NCT03805659     History of Changes
Other Study ID Numbers: 32037
First Posted: January 16, 2019    Key Record Dates
Last Update Posted: January 16, 2019
Last Verified: January 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: Yes
Device Product Not Approved or Cleared by U.S. FDA: No
Pediatric Postmarket Surveillance of a Device Product: No
Product Manufactured in and Exported from the U.S.: No

Keywords provided by Medical College of Wisconsin:
Adult
Primary Progressive Aphasia
High-definition Transcranial Direct Current Stimulation
HD-tDCS
Language
Logopenic
Magnetic Resonance Imaging
MRI
Magnetoencephalography
MEG
Brain
Aphasia

Additional relevant MeSH terms:
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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