Clinical trial NCT04097184: Efficacy of Dorso-lateral Prefrontal Cortex Stimulation by tDCS in Motor Conversion Disorder Patients
Official title: Efficacy of Dorso-lateral Prefrontal Cortex Stimulation by tDCS in Patients With Motor Conversion Disorder - Multicentre Randomized Double Blind Assay
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Conversion Disorder
Lead sponsor: Centre Hospitalier Universitaire de Nīmes
Sponsor class: OTHER
First posted: 2019-09-20
Enrollment: 96
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Prospective multicentre controlled randomized, double-blind, two-arm study
Primary purpose: TREATMENT

Brief summary: Conversion disorder refers to impaired voluntary motor or sensory functions that are not compatible with a well-known neurological condition. This disorder affects up to 30% of hospitalized patients in neurology departments and symptoms persist in 35% of patients after 12 years of evolution. Despite a poor prognosis, no treatments have been validated to date.

The development of non-invasive brain stimulation techniques has allowed the creation of treatments focused on dysfunctional brain regions associated with motor conversion disorder. Hypoactivation of prefrontal dorso-lateral cortex underlies the course of functional motor symptoms. Results of the HYCORE study conducted at Nîmes University Hospital (including 20 patients, clinicaltrial.gov NCT02329626) confirmed these results and related hypoactivation of PFDLC to persistent motor disability at 3 months and 6 months follow-up. Activation of the PFDLC could restore executive control and thus promote the recovery of motor symptoms.

However, in most repeated Transcranial Magnetic Stimulation (rTMS) the primary motor areas were targeted and the clinical improvement was related to self-suggestion induced by the motor response produced.

Among the different techniques, transcranial Direct Current Stimulation (tDCS) is a medical neuromodulation device that delivers a direct, low-intensity electric current to cortical areas, facilitating neuronal activity. Recently, PFDLC stimulation via tDCS has been used to treat several neuropsychiatric disorders and shown to be effective in depression. In addition, this technique has several advantages compared to rTMS: its use is simpler and costs 5 to 8 times less, the device is portable and there is no titration procedure. The tolerance of the tDCS is also better with no risk of epileptic seizure, neuronal depolarization being absent.

Detailed description: Conversion disorder, also called "functional neurological disorder" (DSM-5), refers to impaired voluntary motor or sensory functions that are not compatible with a well-known neurological condition. This disorder affects up to 30% of hospitalized patients in neurology departments (Carson et al. 2000) and the symptoms persist in 35% of patients after 12 years of evolution (Stone et al. 2003). Despite a poor prognosis, no treatments have been validated to date.

The development of non-invasive brain stimulation techniques has allowed the creation of focused treatments on dysfunctional brain regions associated with motor conversion disorder. A hypoactivation of prefrontal dorso-lateral cortex (PFDLC) underlies the course of functional motor symptoms (Spence et al. 2000); (Voon et al.2011); (Conejero et al. 2017). Results of the HYCORE study that the investigators conducted at Nîmes University Hospital (including 20 patients, clinicaltrial.gov NCT02329626) confirmed these results and related hypoactivation of PFDLC to persistent motor disability at 3 months and 6 months follow-up. Activation of the PFDLC could restore executive control and thus promote the recovery of motor symptoms.

However, in the majority of repeated Transcranial Magnetic Stimulation (rTMS) the primary motor areas were targeted (Pollak et al. 2014) and the clinical improvement was related to self-suggestion induced by the motor response produced.

Among the different techniques, transcranial Direct Current Stimulation (tDCS) is a medical neuromodulation device that delivers a direct, low-intensity electric current to cortical areas, facilitating neuronal activity. Recently, PFDLC stimulation via tDCS has been used to treat several neuropsychiatric disorders and shown to be effective in depression. In addition, this technique has several advantages compared to rTMS: its use is simpler and costs 5 to 8 times less, the device is portable and there is no titration procedure. The tolerance of the tDCS is also better with no risk of epileptic seizure, neuronal depolarization being absent.

Eligibility criteria: Inclusion Criteria:

* The patient must have given his/her informed and signed consent.
* The patient is at least (≥) 18 years old and 65 years old at the most (≤). The risk of an increased frequency of somatic comorbidity, drug co-prescription, and cognitive impairment prompts us to limit recruitment to age 65 in this study.
* The patient is hospitalized or followed in consultation.
* Patient is available for a follow-up of 6 months.
* With current DSM-5 criteria for conversion disorder during more than 10 days, motor type (i.e. with paralysis or motor weakness) and initial EDSS score ≥ 3 or initial WHO Score is ≥ 2

Exclusion Criteria:

* The patient is participating in another interventional trial.
* The patient refuses to sign the consent.
* It is impossible to correctly inform the patient.
* The patient is pregnant or breastfeeding.
* Specialized neurological clinical examination and the performing of brain and medullary MRI reveal an organic neurological involvement.
* Current episode of mania, hypomania, diagnosis of substance abuse/dependence (excluding smoking), diagnosis of schizophrenia over lifetime, severe neurological pathology (epilepsy, stroke, brain tumor).
* Patient with a contraindication to MRI (for patients enrolled in Nîmes).
* Acute eczema at the electrodes loci.

Primary outcomes:
measure: Evaluation of the efficacy of tDCS stimulation of the left PFDLC to treat motor disability in patients with conversion disorder 3 months after the intervention.
timeFrame: 3 months after the intervention
Secondary outcomes:
measure: Evaluation of the efficacy on motor symptoms at D7 with NIHSS
timeFrame: 7 days after the intervention
measure: Evaluation of the persistence of efficacy on motor symptoms at 1 month
timeFrame: 1 month after the intervention
measure: Evaluation of the persistence of efficacy on motor symptoms at 3 months
timeFrame: 3 months after the intervention
measure: Evaluation of the persistence of efficacy on motor symptoms at 6 months
timeFrame: 6 months after the intervention
measure: Evaluation of the efficacy on motor disability with EDSS score at D7.
timeFrame: 7 days after the intervention
measure: Evaluation of the persistence of efficacy on motor disability with EDSS at 1 month
timeFrame: 1 month after the intervention
measure: Evaluation of the persistence of efficacy on motor disability with EDSS at 6 months.
timeFrame: 6 month after the intervention
measure: WHO score at D7
timeFrame: 7 days after the intervention
measure: WHO score at 1 month
timeFrame: 1 month after the intervention
measure: WHO score at 3 months
timeFrame: 3 months after the intervention
measure: WHO score at 6 months
timeFrame: 3 months after the intervention
measure: CGI (Clinical Global Impression) scores at Day 7
timeFrame: 7 days after the intervention
measure: CGI (Clinical Global Impression) score at 3 months
timeFrame: 3 months after the intervention
measure: CGI (Clinical Global Impression) score at 6 months
timeFrame: 6 months after the intervention
measure: Modified Rankin (mRS) score at D7
timeFrame: 7 days after the intervention
measure: Modified Rankin (mRS) score at 1 month
timeFrame: 1 month after the intervention
measure: Modified Rankin (mRS) score at 3 months
timeFrame: 3 months after the intervention
measure: Modified Rankin (mRS) score at 6 months
timeFrame: 6 months after the intervention
measure: Evaluation of disability related to abnormal movements - CGI at D7.
timeFrame: 7 days after the intervention
measure: Evaluation of disability related to abnormal movements - CGI at 1 month.
timeFrame: 1 month after the intervention
measure: Evaluation of disability related to abnormal movements - CGI at 3 months.
timeFrame: 3 months after the intervention
measure: Evaluation of disability related to abnormal movements - CGI at 6 months.
timeFrame: 6 months after the intervention
measure: Efficacy on depression and anxiety level assessed with the HAD score (HADS) at D7
timeFrame: 7 days after the intervention
measure: Efficacy on depression and anxiety level assessed with the HAD score (HADS) at 1 month
timeFrame: 1 month after the intervention
measure: Efficacy on depression and anxiety level assessed with the HAD score (HADS) at 3 months .
timeFrame: 3 months after the intervention
measure: Efficacy on depression and anxiety level assessed with the HAD score (HADS) at 6 months.
timeFrame: 6 months after the intervention
measure: Interaction between time from symptom onset to inclusion in the study, initial severity of abnormal movements and efficacy of motor symptom treatment measured with EDSS at D7
timeFrame: 7 days after the intervention
measure: Interaction between time from symptom onset to inclusion in the study, initial severity of abnormal movements and efficacy of motor symptom treatment measured with EDSS at 1 month
timeFrame: 1 month after the intervention
measure: Interaction between time from symptom onset to inclusion in the study, initial severity of abnormal movements and efficacy of motor symptom treatment measured with EDSS at 3 months
timeFrame: 3 months after the intervention
measure: Interaction between time from symptom onset to inclusion in the study, initial severity of abnormal movements and efficacy of motor symptom treatment measured with EDSS at 6 months
timeFrame: 6 months after the intervention
measure: Tolerance to tDCS stimulation D2 - D6 Brunoni
timeFrame: From 2 days to 6 days after the intervention
measure: Correlation between putative modification of motor symptoms and changes in activity (rest / motor imagery task) of the PFDLC monitored by brain fMRI at Day 0 and Day 7.
timeFrame: Day 0 and Day 7
measure: Evaluation of Dissociative Experiences Scale
timeFrame: 7 days after the intervention
measure: Evaluation of Dissociative Experiences Scale
timeFrame: 1 month after the intervention
measure: Evaluation of Dissociative Experiences Scale
timeFrame: 3 month after the intervention
measure: Evaluation of Dissociative Experiences Scale
timeFrame: 6 month after the intervention
measure: Evaluate the evolution of dissociation Experiences Scale
timeFrame: 7 days after the intervention
measure: Evaluate the evolution of dissociation Experiences Scale
timeFrame: 1 month after the intervention
measure: Evaluate the evolution of dissociation Experiences Scale
timeFrame: 3 month after the intervention
measure: Evaluate the evolution of dissociation Experiences Scale
timeFrame: 6 month after the intervention
measure: Evaluate the concordance of the CGI scale between the neurologist's assessment and the psychiatrist's assessment.
timeFrame: 7 days after the intervention
measure: Evaluate the concordance of the CGI scale between the neurologist's assessment and the psychiatrist's assessment.
timeFrame: 1 month after the intervention
measure: Evaluate the concordance of the CGI scale between the neurologist's assessment and the psychiatrist's assessment.
timeFrame: 3 month after the intervention
measure: Evaluate the concordance of the CGI scale between the neurologist's assessment and the psychiatrist's assessment.
timeFrame: 6 month after the intervention
Other outcomes:
Locations:
city: Nîmes
country: France
facility: Centre Hospitalier Universitaire
state: Gard
city: Montpellier
country: France
facility: Hôpital La Colombière Service de Psychiatrie
state: Hérault
city: Montpellier
country: France
facility: CHU de Montpellier Hôpital Gui De Chauliac Service de Neurologie
state: Hérault
city: Montpellier
country: France
facility: Hôpital Lapeyronie
state: Hérault
city: Lyon
country: France
facility: Hospices Civils de Lyon Hôpital Edouard Herriot
city: Nantes
country: France
facility: CHU de Nantes
city: Toulouse
country: France
facility: Clinique St Exupery
city: Paris
country: France
facility: Hôpital Saint-Antoine Service de Psychiatrie APHP
state: Île-de-France
Study officials:
affiliation: CHU de Nîmes (Nîmes University Hospital)
name: Ismael CONEJERO, Dr.
role: PRINCIPAL_INVESTIGATOR
References: