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

NCT03805659 | Completed Results FDA Device

• 1 other identifier: PRO00032037
• Study Type: interventional
• Target: 6
• Locations: 1 country
• Sites: 1

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.

Conditions

Primary Progressive Aphasia

Keywords

Adult; Primary Progressive Aphasia; High-definition Transcranial Direct Current Stimulation; HD-tDCS; Language; Logopenic; Magnetic Resonance Imaging; MRI; Magnetoencephalography; MEG; Brain; Aphasia

Outcome Measures

Primary Outcomes (1)

• Determine Changes in Language Performance After Stimulation Sessions

  Language performance as assessed at baseline and post-stimulation procedure

  Language performance was assessed before and after 2-week intervention and during washout periods

Secondary Outcomes (2)

• Determine the Resting State Language Network-level Changes in Left TPC Functional Connectivity.

  Language network resting state changes were assessed before and after 2-week intervention and during washout periods

• Determine the Neuronal Frequency Distribution and Connectivity Measures Associated With the Left TPC as Assessed by MEG.

  Resting-state neuronal frequencies and synchronizations changes were assessed before and after 2-week intervention and during washout periods

Study Arms (2)

HD-tDCS, then Sham

EXPERIMENTAL

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; Device: Sham

Sham, then HD-tDCS

EXPERIMENTAL

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; Device: Sham

Interventions

HD-tDCS DEVICE

High-Dose transcranial Direct Current Stimulation

Also known as: Soterix MXN-9 High-Definition stimulator

HD-tDCS, then Sham; Sham, then HD-tDCS

Sham DEVICE

Sham sessions (no electric current)

HD-tDCS, then Sham; Sham, then HD-tDCS

Eligibility Criteria

• Age: 45 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• years of age or older.
• Structural brain MRI performed within 3 years prior to enrollment.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Medical College of Wisconsin: lead

Study Sites (1)

The Medical College of Wisconsin

Milwaukee, Wisconsin, 53226, United States

Location

Related Publications (17)

• 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.

  PMID: 26062526 BACKGROUND

• 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.

  PMID: 21606451 BACKGROUND

• 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.

  PMID: 25688082 BACKGROUND

• 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.

  PMID: 23893039 BACKGROUND

• 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.

  PMID: 26232551 BACKGROUND

• 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.

  PMID: 25164766 BACKGROUND

• 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.

  PMID: 18633132 BACKGROUND

• 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.

  PMID: 16267224 BACKGROUND

• 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.

  PMID: 17287508 BACKGROUND

• 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.

  PMID: 20648973 BACKGROUND

• 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.

  PMID: 23097644 BACKGROUND

• 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.

  PMID: 28714545 BACKGROUND

• 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.

  PMID: 23370061 BACKGROUND

• 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.

  PMID: 25547776 BACKGROUND

• 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.

  PMID: 23149292 BACKGROUND

• 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.

  PMID: 27198577 BACKGROUND

• 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.

  PMID: 40070907 DERIVED

MeSH Terms

Conditions

Aphasia, Primary Progressive; Language; Aphasia

Condition Hierarchy (Ancestors)

Dementia; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Speech Disorders; Language Disorders; Communication Disorders; Neurobehavioral Manifestations; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Neurocognitive Disorders; Mental Disorders; Communication; Behavior

Results Point of Contact

• Title: Peter Kraegel
• Organization: Medical College of Wisconsin

pkraegel@mcw.edu

414-955-0657

Study Officials

• Elias Granadillo

  The Medical College of Wisconsin

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: 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.
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor

Model Details: 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.

Study Record Dates

• First Submitted: December 27, 2018
• First Posted: January 16, 2019
• Study Start: February 24, 2020
• Primary Completion: May 18, 2022
• Study Completion: May 18, 2022
• Last Updated: June 11, 2024
• Results First Posted: June 11, 2024

Record last verified: 2024-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)