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

Primary Progressive Aphasia Clinical Trial

Official title:

High-Definition Transcranial Direct Current Stimulation (HD-tDCS) in Logopenic Variant Primary Progressive Aphasia (lvPPA): Effects on Language and Neural Mechanisms

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03805659
• Other study ID #: PRO00032037
• Status: Completed
• Phase: N/A
• Start date: February 24, 2020
• Est. completion date: May 18, 2022

Study information

• Verified date: May 2024
• Source: Medical College of Wisconsin
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 6
• Est. completion date: May 18, 2022
• Est. primary completion date: May 18, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 45 Years and older

Eligibility

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.

Related Conditions & MeSH terms

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

Intervention

Device:
• HD-tDCS
High-Dose transcranial Direct Current Stimulation
• Sham
Sham sessions (no electric current)

Locations

Country	Name	City	State
United States	The Medical College of Wisconsin	Milwaukee	Wisconsin

Sponsors (1)

Lead Sponsor	Collaborator
Medical College of Wisconsin

Country where clinical trial is conducted

United States, 

References & Publications (16)

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

* Note: There are 16 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Determine the Resting State Language Network-level Changes in Left TPC Functional Connectivity.	Language network resting state changes after stimulation procedure	Language network resting state changes were assessed before and after 2-week intervention and during washout periods
Secondary	Determine the Neuronal Frequency Distribution and Connectivity Measures Associated With the Left TPC as Assessed by MEG.	Resting-state neuronal frequencies and synchronizations changes after stimulation procedure	Resting-state neuronal frequencies and synchronizations changes were assessed before and after 2-week intervention and during washout periods