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

NCT ID: NCT03805659

Last Updated: 2024-06-11

Study Results

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

NA

Total Enrollment

6 participants

Study Classification

INTERVENTIONAL

Study Start Date

2020-02-24

Study Completion Date

2022-05-18

Brief Summary

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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.

Detailed Description

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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.

Conditions

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Primary Progressive Aphasia

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

CROSSOVER

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.
Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors
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.

Study Groups

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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).

Group Type EXPERIMENTAL

HD-tDCS

Intervention Type DEVICE

High-Dose transcranial Direct Current Stimulation

Sham

Intervention Type DEVICE

Sham sessions (no electric current)

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).

Group Type EXPERIMENTAL

HD-tDCS

Intervention Type DEVICE

High-Dose transcranial Direct Current Stimulation

Sham

Intervention Type DEVICE

Sham sessions (no electric current)

Interventions

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HD-tDCS

High-Dose transcranial Direct Current Stimulation

Intervention Type DEVICE

Sham

Sham sessions (no electric current)

Intervention Type DEVICE

Other Intervention Names

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Soterix MXN-9 High-Definition stimulator

Eligibility Criteria

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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 3 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.
Minimum Eligible Age

45 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Medical College of Wisconsin

OTHER

Sponsor Role lead

Responsible Party

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Elias Granadillo Deluque

Assistant Professor

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Elias Granadillo

Role: PRINCIPAL_INVESTIGATOR

The Medical College of Wisconsin

Locations

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The Medical College of Wisconsin

Milwaukee, Wisconsin, United States

Site Status

Countries

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United States

References

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Tippett DC, Hillis AE, Tsapkini K. Treatment of Primary Progressive Aphasia. Curr Treat Options Neurol. 2015 Aug;17(8):362. doi: 10.1007/s11940-015-0362-5.

Reference Type BACKGROUND
PMID: 26062526 (View on PubMed)

Rogalski E, Cobia D, Harrison TM, Wieneke C, Weintraub S, Mesulam MM. Progression of language decline and cortical atrophy in subtypes of primary progressive aphasia. Neurology. 2011 May 24;76(21):1804-10. doi: 10.1212/WNL.0b013e31821ccd3c.

Reference Type BACKGROUND
PMID: 21606451 (View on PubMed)

Abel S, Weiller C, Huber W, Willmes K, Specht K. Therapy-induced brain reorganization patterns in aphasia. Brain. 2015 Apr;138(Pt 4):1097-112. doi: 10.1093/brain/awv022. Epub 2015 Feb 15.

Reference Type BACKGROUND
PMID: 25688082 (View on PubMed)

Villamar MF, Volz MS, Bikson M, Datta A, Dasilva AF, Fregni F. Technique and considerations in the use of 4x1 ring high-definition transcranial direct current stimulation (HD-tDCS). J Vis Exp. 2013 Jul 14;(77):e50309. doi: 10.3791/50309.

Reference Type BACKGROUND
PMID: 23893039 (View on PubMed)

Meyer AM, Snider SF, Campbell RE, Friedman RB. Phonological short-term memory in logopenic variant primary progressive aphasia and mild Alzheimer's disease. Cortex. 2015 Oct;71:183-9. doi: 10.1016/j.cortex.2015.07.003. Epub 2015 Jul 16.

Reference Type BACKGROUND
PMID: 26232551 (View on PubMed)

Pillay SB, Stengel BC, Humphries C, Book DS, Binder JR. Cerebral localization of impaired phonological retrieval during rhyme judgment. Ann Neurol. 2014 Nov;76(5):738-46. doi: 10.1002/ana.24266. Epub 2014 Sep 19.

Reference Type BACKGROUND
PMID: 25164766 (View on PubMed)

Gorno-Tempini ML, Brambati SM, Ginex V, Ogar J, Dronkers NF, Marcone A, Perani D, Garibotto V, Cappa SF, Miller BL. The logopenic/phonological variant of primary progressive aphasia. Neurology. 2008 Oct 14;71(16):1227-34. doi: 10.1212/01.wnl.0000320506.79811.da. Epub 2008 Jul 16.

Reference Type BACKGROUND
PMID: 18633132 (View on PubMed)

Dancause N, Barbay S, Frost SB, Plautz EJ, Chen D, Zoubina EV, Stowe AM, Nudo RJ. Extensive cortical rewiring after brain injury. J Neurosci. 2005 Nov 2;25(44):10167-79. doi: 10.1523/JNEUROSCI.3256-05.2005.

Reference Type BACKGROUND
PMID: 16267224 (View on PubMed)

Sonty SP, Mesulam MM, Weintraub S, Johnson NA, Parrish TB, Gitelman DR. Altered effective connectivity within the language network in primary progressive aphasia. J Neurosci. 2007 Feb 7;27(6):1334-45. doi: 10.1523/JNEUROSCI.4127-06.2007.

Reference Type BACKGROUND
PMID: 17287508 (View on PubMed)

Datta A, Bansal V, Diaz J, Patel J, Reato D, Bikson M. Gyri-precise head model of transcranial direct current stimulation: improved spatial focality using a ring electrode versus conventional rectangular pad. Brain Stimul. 2009 Oct;2(4):201-7, 207.e1. doi: 10.1016/j.brs.2009.03.005.

Reference Type BACKGROUND
PMID: 20648973 (View on PubMed)

Datta A, Truong D, Minhas P, Parra LC, Bikson M. Inter-Individual Variation during Transcranial Direct Current Stimulation and Normalization of Dose Using MRI-Derived Computational Models. Front Psychiatry. 2012 Oct 22;3:91. doi: 10.3389/fpsyt.2012.00091. eCollection 2012.

Reference Type BACKGROUND
PMID: 23097644 (View on PubMed)

Muthalib M, Besson P, Rothwell J, Perrey S. Focal Hemodynamic Responses in the Stimulated Hemisphere During High-Definition Transcranial Direct Current Stimulation. Neuromodulation. 2018 Jun;21(4):348-354. doi: 10.1111/ner.12632. Epub 2017 Jul 17.

Reference Type BACKGROUND
PMID: 28714545 (View on PubMed)

Edwards D, Cortes M, Datta A, Minhas P, Wassermann EM, Bikson M. Physiological and modeling evidence for focal transcranial electrical brain stimulation in humans: a basis for high-definition tDCS. Neuroimage. 2013 Jul 1;74:266-75. doi: 10.1016/j.neuroimage.2013.01.042. Epub 2013 Jan 28.

Reference Type BACKGROUND
PMID: 23370061 (View on PubMed)

Richardson J, Datta A, Dmochowski J, Parra LC, Fridriksson J. Feasibility of using high-definition transcranial direct current stimulation (HD-tDCS) to enhance treatment outcomes in persons with aphasia. NeuroRehabilitation. 2015;36(1):115-26. doi: 10.3233/NRE-141199.

Reference Type BACKGROUND
PMID: 25547776 (View on PubMed)

Kuo HI, Bikson M, Datta A, Minhas P, Paulus W, Kuo MF, Nitsche MA. Comparing cortical plasticity induced by conventional and high-definition 4 x 1 ring tDCS: a neurophysiological study. Brain Stimul. 2013 Jul;6(4):644-8. doi: 10.1016/j.brs.2012.09.010. Epub 2012 Oct 13.

Reference Type BACKGROUND
PMID: 23149292 (View on PubMed)

Hogeveen J, Grafman J, Aboseria M, David A, Bikson M, Hauner KK. Effects of High-Definition and Conventional tDCS on Response Inhibition. Brain Stimul. 2016 Sep-Oct;9(5):720-729. doi: 10.1016/j.brs.2016.04.015. Epub 2016 Apr 22.

Reference Type BACKGROUND
PMID: 27198577 (View on PubMed)

Granadillo ED, Fellmeth M, Youssofzadeh V, Heffernan J, Shah-Basak PP, Pillay SB, Ustine C, Kraegel P, Schold S, Mueller KD, Ikonomidou C, Okonkwo O, Raghavan M, Binder JR. Behavioral and neural effects of temporoparietal high-definition transcranial direct current stimulation in logopenic variant primary progressive aphasia: a preliminary study. Front Psychol. 2025 Feb 25;16:1492447. doi: 10.3389/fpsyg.2025.1492447. eCollection 2025.

Reference Type DERIVED
PMID: 40070907 (View on PubMed)

Provided Documents

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Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

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PRO00032037

Identifier Type: -

Identifier Source: org_study_id

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