Clinical trial NCT05671848: Electroclinical Correlates in Essential Tremor
Official title: Study of the Activity of the Ventral Intermediate Nucleus of the Thalamus Under Ecological Conditions in Essential Tremor.
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Essential Tremor
Keywords: Essential Tremor
Local field potentials
Deep Brain Stimulation
Lead sponsor: University Hospital, Bordeaux
Sponsor class: OTHER
Collaborators: name: MINDig
First posted: 2023-01-05
Enrollment: 10
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Single-center, open-label, prospective cohort pilot study.
Primary purpose: BASIC_SCIENCE

Brief summary: Essential tremor (ET) is a neurological disorder that affects nearly 0.9% of the world's population. High-frequency Deep Brain Stimulation (DBS) of the ventral-intermediate nuclei of the thalamus (VIM) has been proven as an effective second-line treatment for severe forms of ET.

The arrival on the market of the PERCEPT™ (new stimulator/recorder, Medtronic, Minneapolis, USA) now allows, in addition to the stimulation delivery, the recording of intracerebral activity at a distance from surgery, in a non-invasive way and in ecological condition at home. Investigators aim at recording the variations of thalamic Local Field Potentials (LFP) oscillations, in ecological condition, during rest and movement, with and without deep brain stimulation, once a week, between M3 and M6 post surgery.

Detailed description: Essential tremor (ET) is a neurological disorder that affects nearly 0.9% of the world's population, including 300,000 people in France alone. Patients who suffer from this condition usually present an upper limb tremor during voluntary motor activities but not at rest. The pharmacological treatments proposed for this condition are only effective in about 50% of patients, and this effectiveness is often only partial or observed at the cost of unacceptable side effects. Since the end of the 1980's, high-frequency deep brain stimulation (DBS) of the ventral-intermediate nuclei of the thalamus (VIM) has been proposed as an effective second-line treatment for severe forms of ET. However, some neuro-stimulated patients experience a recurrence of their tremor and may complain of an increase in pre-existing cerebellar ataxia. The mechanisms underlying these phenomena are still debated, but the fact that VIM stimulation is applied in a chronic and undifferentiated manner seems to play a determining role. One way to circumvent these phenomena could be to stimulate the VIM only during movement since the tremor in this condition is an action or postural tremor. This type of "closed-loop therapy" requires one or more intracerebral tremor biomarkers that can be reliably recognized and used to automatically trigger or modulate the intensity of VIM stimulation only when necessary. In a preliminary study in 10 patients, the investigators of Bordeaux university hospital were able to demonstrate the existence of potential intracerebral biomarkers of tremor under experimental conditions,in the immediate postoperative period (Guehl et al. 2022, submitted). The arrival on the market of the PERCEPT™ (new stimulator/recorder, Medtronic, Minneapolis, USA) now allows, in addition to treating patients with DBS, the recording of intracerebral activity at a distance from surgery, in a non-invasive way and in ecological condition at home. This study aim at recording the variations of thalamic oscillations, in ecological condition, during rest and movement, with and without deep brain stimulation. These measurements will be performed once a week during the 12 weeks of the late post-operative period (from 3 to 6 months), in order to ensure the reproducibility of the results. The signal processing and analysis will be performed in a blind manner to the patient's activity and stimulation condition.

Eligibility criteria: Inclusion Criteria:

* Advanced disabling and drug-resistant tremor
* Receiving deep brain stimulation treatment with implantation of the PERCEPT™ device according to standard care
* Chronic progressive cardiac, renal, hematological or pulmonary diseases under treatment.
* Patient aged between 18 to 75 years
* Normal brain MRI
* MATTIS score ≥ 130/144 or MOCA ≥ 24/30
* Subject affiliated with or benefiting from a social security plan
* Free, informed and written consent signed by the participant and the investigator (at the latest on the day of inclusion and before any examination required by the research)

Exclusion Criteria:

* Major depressive syndrome (Beck scale \> 20)
* MRI showing significant brain atrophy or significant hypersignals
* Pregnant or breastfeeding women
* Being unable to give personal consent
* Be subject to a measure of legal protection (curatorship, guardianship) or placed under judicial protection.

Primary outcomes:
measure: Recorded signal quality
timeFrame: 6 months (M6) after surgery (M0)
Secondary outcomes:
measure: presence or absence of brain oscillations
timeFrame: 6 months (M6) after surgery (M0)
measure: Power spectral density (PSD)
timeFrame: 6 months (M6) after surgery (M0)
measure: Location of the electrodes
timeFrame: 1 month (M1) after surgery (M0)
measure: Evaluation of the efficacy of VIM DBS in the ET
timeFrame: 3 months (M3) after surgery (M0)
Other outcomes:
Locations:
city: Bordeaux
country: France
facility: CHU de Bordeaux
Study officials:
affiliation: University Hospital, Bordeaux
name: Dominique GUELH, Pr
role: STUDY_DIRECTOR
affiliation: University Hospital, Bordeaux
name: Edouard COURTIN, Dr
role: PRINCIPAL_INVESTIGATOR
affiliation: MINDig
name: Mahmoud HASSAN, Dr
role: STUDY_CHAIR
References: