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

Overview

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.

Interventions

• Device Neurostimulation with non-implanted electrodes
  Neurostimulation with non-implanted electrodes

Primary outcome measures

• 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. [Time frame: 3 months after the intervention]

Secondary outcome measures (12)

• Evaluation of the efficacy on motor symptoms at D7 with NIHSS [Time frame: 7 days after the intervention]
• Evaluation of the persistence of efficacy on motor symptoms at 1 month [Time frame: 1 month after the intervention]
• Evaluation of the persistence of efficacy on motor symptoms at 3 months [Time frame: 3 months after the intervention]
• Evaluation of the persistence of efficacy on motor symptoms at 6 months [Time frame: 6 months after the intervention]
• Evaluation of the efficacy on motor disability with EDSS score at D7. [Time frame: 7 days after the intervention]
• Evaluation of the persistence of efficacy on motor disability with EDSS at 1 month [Time frame: 1 month after the intervention]
• Evaluation of the persistence of efficacy on motor disability with EDSS at 6 months. [Time frame: 6 month after the intervention]
• WHO score at D7 [Time frame: 7 days after the intervention]
• WHO score at 1 month [Time frame: 1 month after the intervention]
• WHO score at 3 months [Time frame: 3 months after the intervention]
• WHO score at 6 months [Time frame: 3 months after the intervention]
• CGI (Clinical Global Impression) scores at Day 7 [Time frame: 7 days after the intervention]

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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Quadruple blind

Primary purpose

Treatment

Study locations

France · 8 centers

• Centre Hospitalier Universitaire — Nîmes
• Hôpital La Colombière Service de Psychiatrie — Montpellier
• CHU de Montpellier Hôpital Gui De Chauliac Service de Neurologie — Montpellier
• Hôpital Lapeyronie — Montpellier
• Hospices Civils de Lyon Hôpital Edouard Herriot — Lyon
• CHU de Nantes — Nantes
• Clinique St Exupery — Toulouse
• Hôpital Saint-Antoine Service de Psychiatrie APHP — Paris

Identifiers

NCT: NCT04097184 · PHRC-N/2018/IC-01

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗