Evaluation of a Transcranial Stimulation With Direct Current on Language Disorders in Semantic Dementia

NCT03481933 | Unknown

• 1 other identifier: P160937J
• Study Type: interventional
• Target: 80
• Locations: 1 country
• Sites: 2

Brief Summary

Within the spectrum of fronto-temporal lobar degeneration (FTLD) semantic dementia (SD) causes profound language dysfunction. SD damages semantic processing typically in the temporal poles (anterior temporal lobes, ATL). It is an early onset disease (often before 65 years of age) affecting about 4000 patients in France and for which no validated treatment is available. For several years a growing number of studies have explored the effects of transcranial stimulation (TCS) on aphasic patients following stroke. Several studies have targeted left-sided language areas and/or homotopical right-sided regions with excitatory or inhibitory TCS, respectively, according to the principle of inter-hemispheric inhibition. In addition, repetitive multi-day TCS has provided evidence for long-lasting language effects (\>6 months) presumably linked to stimulation-induced neuroplasticity. Such investigations have provided promising results and have demonstrated that the stimulation site is a determining factor by showing that stimulation of cortical areas belonging to the language network usually results in more convincing effects than stimulating areas outside that network. Despite these findings the use of TCS in degenerative language diseases, such as primary progressive aphasias including SD, has only been explored in few small cohort studies and, surprisingly, they have not targeted language-related cortices. This project proposes the application of multi-day repetitive TCS with direct current (tDCS) in a large population of SD patients (N=60). It is built on a exploratory investigation of our team which has used three single tDCS sessions in a double-blind sham-controlled study. Excitatory and inhibitory tDCS to the left and right temporal pole, respectively, demonstrated highly significant transient effects (20 min) on semantic processing in 12 SD patients, providing 'proof of concept' and the rationale for this project. The aim here consists of using repetitive multi-day tDCS for a potential therapeutic outcome leading to long-lasting semantic improvement via neuroplasticity. The project is grounded on 2 hypotheses: i) tDCS to temporal poles (left-excitatory, right-inhibitory) reactivates semantic processing in SD, ii) repetitive tDCS during ten days could induce neuroplasticity and therapeutic language improvement.

Conditions

Semantic Dementia

Outcome Measures

Primary Outcomes (1)

• Significant improvement of semantic performances on the experimental 'semantic matching test'

  The 'semantic matching test' assesses semantic processing in the verbal and visual modality. Outcome measure will be the difference between performance on the test at base line and two weeks after tDCS: composite score of accuracy on the test.

  15 days

Secondary Outcomes (3)

• Significant modulation of semantic performances on the 'semantic matching test'

  3 days, 4 months

• significant modulation of cortical metabolism and functional connectivity

  2 weeks

• Detection of a potential outcome difference between left-excitatory and right-inhibitory tDCS

  15 days, 4 months

Study Arms (3)

1:left-excitatory tDCS

EXPERIMENTAL

20 SD patients who receive left-excitatory trans cranial stimulation

Device: Transcranial stimulation

2:right-inhibitory tDCS

ACTIVE COMPARATOR

20 SD patients who receive right-inhibotory trans cranial stimulation

Device: Transcranial stimulation

3:sham tDCS

SHAM COMPARATOR

20 SD patients who receive sham stimulation

Device: Transcranial stimulation

Interventions

Transcranial stimulation DEVICE

1. 10 days of stimulation (20min, 1.59mA) in double-blind sham-controlled. 3 arms (N=20 in each arm): * left-excitatory tDCS (N=20) * right-inhibitory tDCS (N=20) * sham tDCS (N=20) 2. 4 language/semantic evaluations: base-line; 3 days; 2 weeks; 4 months post-tDCS 3. 2 MRI/PET acquisitions: pre-stimulation (base-line); 2 weeks post-tDCS

1:left-excitatory tDCS; 2:right-inhibitory tDCS; 3:sham tDCS

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• SD-Patients:
• Patients fulfilling the international diagnosis criteria of SD (Gorno-Tempini et al., 2011): fluent speech, single word comprehension and naming deficit, +/- object recognition deficits, +/- surface agraphia or alexia. Absence of phonemic paraphasias, agrammatism and word apraxia.
• Age \> 18 years old.
• Patients have given their informed written consent.
• Affiliation to a social security regime.
• Healthy controls:
• Age \>18 years old
• Subjects have given their informed written consent.
• Subjects selected according to the matching criteria (age, sex, handedness and number of years of education).
• Affiliation to a social security regime

You may not qualify if:

• SD-Patients:
• MADRS ≥ 20 (major depressive syndrome according to the DSM-IV-R criteria)
• MMS \< 10/30
• FAB \< 7/18
• BDAE aphasia severity rating scale \< 3/5
• Patients not having French as their mother tongue
• Other neurological pathology or general disorder or major physical deficits than can interfere with cognitive functioning
• MRI or PET contraindication, 18-FDG contraindication
• The patient should not participate simultaneously in another brain therapeutic trial (possibility of bias between stimulation and evaluation of the effect on language / semantic processes)
• \- tDCS contraindications: epilepsy antecedents, presence of epilepsy risk factors (known alcoholism or metabolic troubles, antecedents of head injury or chirurgical intervention on the brain or the skull), skin lesions of the scalp, skull metal implants.
• \- Patients under curatorship or tutorship
• \- Women whose pregnancy is known or who do not have effective contraception if they are of reproductive age (checked by urinary test), breastfeeding.
• Healthy controls:
• Subjects not having French as their mother tongue
• Subjects having a neurological or psychiatric disease or major deficits than can interfere with cognitive functioning

Sponsors & Collaborators

• Assistance Publique - Hôpitaux de Paris: lead

Study Sites (2)

Département de Neurologie - Centre des maladies neurologiques, cognitives et comportementales

Paris, 75013, France

RECRUITING

Hôpital de la Pitié-Salpétrière

Paris, 75013, France

RECRUITING

Related Publications (1)

• Sanches C, Levy R, Benisty S, Volpe-Gillot L, Habert MO, Kas A, Stroer S, Pyatigorskaya N, Kaglik A, Bourbon A, Dubois B, Migliaccio R, Valero-Cabre A, Teichmann M. Testing the therapeutic effects of transcranial direct current stimulation (tDCS) in semantic dementia: a double blind, sham controlled, randomized clinical trial. Trials. 2019 Nov 20;20(1):632. doi: 10.1186/s13063-019-3613-z.

  PMID: 31747967 DERIVED

MeSH Terms

Conditions

Frontotemporal Dementia

Condition Hierarchy (Ancestors)

Frontotemporal Lobar Degeneration; Dementia; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; TDP-43 Proteinopathies; Neurodegenerative Diseases; Proteostasis Deficiencies; Metabolic Diseases; Nutritional and Metabolic Diseases; Neurocognitive Disorders; Mental Disorders

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: left-excitatory tDCS ; right-inhibitory tDCS; sham tDCS (placebo)

Study Record Dates

• First Submitted: March 9, 2018
• First Posted: March 29, 2018
• Study Start: May 16, 2018
• Primary Completion: September 1, 2024
• Study Completion: September 1, 2024
• Last Updated: January 17, 2024

Record last verified: 2023-03

Data Sharing

• IPD Sharing: Will not share

Locations

FR (2)