ClinicalTrials.gov
ClinicalTrials.gov Menu

Evaluation of a Transcranial Stimulation With Direct Current on Language Disorders in Semantic Dementia (STIM-SD)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT03481933
Recruitment Status : Not yet recruiting
First Posted : March 29, 2018
Last Update Posted : March 29, 2018
Sponsor:
Information provided by (Responsible Party):
Assistance Publique - Hôpitaux de Paris

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.


Condition or disease Intervention/treatment Phase
Semantic Dementia Device: Transcranial stimulation Not Applicable

  Show Detailed Description

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 80 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: left-excitatory tDCS ; right-inhibitory tDCS; sham tDCS (placebo)
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Investigation of the Therapeutic Value of Transcranial Stimulation With Direct Current on Language Disorders in Semantic Dementia
Estimated Study Start Date : March 2018
Estimated Primary Completion Date : August 2021
Estimated Study Completion Date : August 2021


Arm Intervention/treatment
Experimental: 1:left-excitatory tDCS
20 SD patients who receive left-excitatory trans cranial stimulation
Device: Transcranial stimulation
  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

Active Comparator: 2:right-inhibitory tDCS
20 SD patients who receive right-inhibotory trans cranial stimulation
Device: Transcranial stimulation
  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

Sham Comparator: 3:sham tDCS
20 SD patients who receive sham stimulation
Device: Transcranial stimulation
  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




Primary Outcome Measures :
  1. Significant improvement of semantic performances on the experimental 'semantic matching test' [ Time Frame: 15 days ]
    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.


Secondary Outcome Measures :
  1. Significant modulation of semantic performances on the 'semantic matching test' [ Time Frame: 3 days, 4 months ]
    Outcome measures will be the difference of performance on the test between base line and 1) 3 days after tDCS, 2) 4 months after tDCS: composite score of accuracy on the test.

  2. significant modulation of cortical metabolism and functional connectivity [ Time Frame: 2 weeks ]
    significant modulation of cortical metabolism on FDG-PET and functional connectivity on fMRI resting-state, comparing base-line and the two weeks after tDCS

  3. Detection of a potential outcome difference between left-excitatory and right-inhibitory tDCS [ Time Frame: 15 days, 4 months ]
    performance difference on the accuracy score of the semantic matching task comparing left and right tDCS



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

SD-Patients:

  1. 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.
  2. Age > 18 years old.
  3. Patients have given their informed written consent.
  4. Affiliation to a social security regime.

Healthy controls:

  1. Age >18 years old
  2. Subjects have given their informed written consent.
  3. Subjects selected according to the matching criteria (age, sex, handedness and number of years of education).
  4. Affiliation to a social security regime

Exclusion Criteria:

SD-Patients:

  1. MADRS ≥ 20 (major depressive syndrome according to the DSM-IV-R criteria)
  2. MMS < 15/30
  3. FAB < 10/18
  4. BDAE aphasia severity rating scale < 3/5
  5. Patients not having French as their mother tongue
  6. Patients with left handedness
  7. Other neurological pathology or general disorder or major physical deficits than can interfere with cognitive functioning
  8. MRI or PET contraindication, 18-FDG contraindication
  9. Cerebral MRI data compatible with a pathological process other than the one related to SD (Vascular, traumatic, tumoral, infectious, or metabolic brain injury). A moderate or discrete leukoaraiosis will not be considered as a non- inclusion criterion (patients with a Fazekas and Schmidt [Fazekas et al., 1998a; fazekas et al., 1998b],stage >2 for hypersignals of the periventricular and deep white matter will not be included)
  10. 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)
  11. - 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.
  12. - Patients under curatorship or tutorship
  13. - 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:

  1. Subjects not having French as their mother tongue
  2. Subjects having a neurological or psychiatric disease or major deficits than can interfere with cognitive functioning
  3. MRI or PET contraindication, 18-FDG contraindication
  4. Women whose pregnancy is known or who do not have effective contraception if they are of reproductive age (checked by urinary test), breastfeeding.

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): NCT03481933


Locations
France
Département de Neurologie - Centre des maladies neurologiques, cognitives et comportementales
Paris, France, 75013
Hôpital de la Pitié-Salpétrière
Paris, France, 75013
Sponsors and Collaborators
Assistance Publique - Hôpitaux de Paris

Responsible Party: Assistance Publique - Hôpitaux de Paris
ClinicalTrials.gov Identifier: NCT03481933     History of Changes
Other Study ID Numbers: P160937J
First Posted: March 29, 2018    Key Record Dates
Last Update Posted: March 29, 2018
Last Verified: March 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
Frontotemporal Dementia
Pick Disease of the Brain
Dementia
Language Disorders
Aphasia, Primary Progressive
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Neurocognitive Disorders
Mental Disorders
Communication Disorders
Neurobehavioral Manifestations
Neurologic Manifestations
Signs and Symptoms
Frontotemporal Lobar Degeneration
TDP-43 Proteinopathies
Neurodegenerative Diseases
Proteostasis Deficiencies
Metabolic Diseases
Aphasia
Speech Disorders