Transcranial Ultrasound Therapy of Essential Tremor

NCT04074031 | Unknown

• 1 other identifier: APHP190407
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 1

Brief Summary

Context. Essential tremor (ET) is a common disease, disabling in severe forms and resistant to drug treatment. In patients with severe ET, invasive neurosurgical technique such as deep brain stimulation of the Ventral Intermediate (VIM) nucleus of the thalamus is used. Focused ultrasound therapy, creating a small lesion of VIM represents an effective therapeutic alternative of low morbidity with the advantage of not requiring the opening of the skull and penetration into the brain. This therapy is performed under stereotactic guidance. Validation of the target before lesioning is done by testing the clinical effect by a gradual increase in temperature, resulting in tremor reduction. However, the gradual temperature increase in the targeting phase is suboptimal because it can decrease the efficiency of the lesioning procedure. The aim of this research project is to test an innovation of fundamental physics developed by the Langevin Institute, which would allow the reversible modulation of nerve tissue by ultrasonic waves without heating, to predict the effectiveness of treatment of the chosen target within the VIM before creating an irreversible lesion. Methodology: Fifteen patients with severe and resistant essential tremor will be included in the study. A multimodal MRI will be performed for target calculation using several targeting methods for VIM developed during step 1. For each target, the application of neuro-modulation by ultrasound will allow determine the effect obtained on the tremor (quantified with adequate clinical scales - as Tremor rating scale (CRST), and the recording of electromyographic activity of the upper limbs) and the absence of side effects. A definitive millimetric lesion will be performed at the level of the most relevant target in order to maintain the clinical effect obtained. The procedure will be controlled by thermal MRI sequences. Post-therapy clinical and MRI multimodal follow-up will take place on D1, D7, M1, M2, M3, M6, M12 and M24. Perspectives and Innovation: This project will test clinically the low intensity ultrasound neuromodulation jointly developed by the Langevin Institute and the Brain and Spine Institute ( ICM) in order to refine the targeting procedure of high intensity transcranial focused ultrasound therapy. In perspective, reversible neuromodulation performed in vivo in humans represents a considerable advance in the exploration and future treatment of neurological and psychiatric diseases such as depression. The translational collaboration between the physicists of the Langevin Institute, the ICM and the medical services of the Pitié-Salpêtrière guarantees the feasibility and quality of this first joint therapeutic trial.

Conditions

Essential Tremor

Outcome Measures

Primary Outcomes (1)

• The main objective is to evaluate the efficacy of Vim lesion produced by transcranial focused ultrasound on contralateral upper limb tremor at the 3-month procedure.

  The primary endpoint is the reduction of the severity of essential tremor measured by the clinical assessment of contralateral upper limb tremor at the lesion quantified by CRST A and B at V5 (3 months) compared with V1.

  3 MONTHS

Secondary Outcomes (2)

• Interest of neuromodulation effect for the prediction of the final clinical effect

  3 MONTHS

• Adverse events

  24 MONTHS

Study Arms (1)

minimally invasive method for performing thalamotomy

EXPERIMENTAL

We will study patients with essential tremor with significant disability despite well-conducted drug therapy who have a contraindication to deep brain stimulation or who refuse treatment. In this population, unilateral thalamotomy of Vim by radiosurgery is already considered a valid indication and performed routinely with proven efficacy and morbidity deemed acceptable. It is therefore the population of choice to evaluate for the first time in France the efficacy and safety of a new, minimally invasive method for performing thalamotomy: targeted ultrasound thermal injury at high intensity. This same population will also make it possible to study, for the first time in humans in this indication, the potential of neuromodulation by low frequency low frequency ultrasound beams to improve the guidance before the lesion is achieved.

Device: Transcranial Ultrasound Therapy (Exablate® 4000 Type 1.1)

Interventions

Transcranial Ultrasound Therapy (Exablate® 4000 Type 1.1) DEVICE

The Exablate® 4000 Type 1.1 model designed for noninvasive ablation of brain tissue is an MRI-guided transcranial ultrasound system (MRgFUS). The goal of the Exablate Neuro system is to precisely guide the focus of the ultrasound energy on the target region. The focused ultrasound energy is then repeatedly transmitted to the target until the desired result is achieved. Targeting is performed using MRI acquired during treatment. The treatment process is constantly monitored by closed-loop thermal feedback in real time, under the supervision of the treating physician. Once targeting is complete, the treatment outcome is confirmed by MRI sequences immediately after treatment. The Exablate Neuro is compatible with Siemens 3 Tesla MRI.

minimally invasive method for performing thalamotomy

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Men and women, aged 18 to 80
• Diagnosis of essential tremor according to the criteria of the Consensus Statement of the Movement Disorders Society (MDS)
• Patients with significant disability related to their essential Tremor, despite well-conducted medical treatment
• Contraindication or refusal or preference of deep brain stimulation
• Patient receiving Social Security or Universal Medical Coverage or any equivalent plan
• Person who voluntarily and knowingly agreed to participate in the study (signing of a written consent)

You may not qualify if:

• Inability to stop anticoagulant or antiplatelet therapy or any other medication that may increase the risk of bleeding during the 2 weeks prior to the procedure
• Current state of health causing bleeding and / or abnormal coagulopathy
• Unstable cardiac pathology or severe hypertension that cannot be controlled by medication (diastolic blood pressure\> 100 with drugs).
• Contraindications to magnetic resonance imaging such as non-compatible implanted metal devices (including pacemakers), size limits, etc. including presence of implants in the brain or skull)
• Known hypersensitivity to local anesthetics (Xylocaine 20mg / ml)
• Important claustrophobia that cannot be managed with mild medication
• Inability to maintain prolonged stationary supine position necessary for treatment (3-4 hours)
• Woman of childbearing age without means of contraception
• Pregnant or lactating woman
• Major persons subject to a measure of legal protection (guardianship, curators or under the protection of justice)
• Patients under AME (state medical aid) (except if exemption from affiliation)
• Patient cannot communicate with the doctor during the treatment procedure
• Subjects with behavior compatible with the abuse of ethanol or psychoactive substances
• Progressive neurological pathology other than TE, stroke or cerebral hemorrhage \< 6 months, multiple stroke ATCD, brain tumor or intracranial aneurysm
• Patients who have taken in the last 6 months drugs lowering the epileptogenic threshold significantly (CNS stimulants, sympathomimetics, neuroleptics, imipraminic antidepressants, amantadine, fampridine, fluoroquinolones, mefloquine)

Sponsors & Collaborators

• Assistance Publique - Hôpitaux de Paris: lead

Study Sites (1)

Hôpital Pitié Salpétrière

Paris, 75013, France

Location

Related Publications (3)

• Gallea C, Popa T, Garcia-Lorenzo D, Valabregue R, Legrand AP, Marais L, Degos B, Hubsch C, Fernandez-Vidal S, Bardinet E, Roze E, Lehericy S, Vidailhet M, Meunier S. Intrinsic signature of essential tremor in the cerebello-frontal network. Brain. 2015 Oct;138(Pt 10):2920-33. doi: 10.1093/brain/awv171. Epub 2015 Jun 26.

  PMID: 26115677 BACKGROUND

• Bardinet E, Belaid H, Grabli D, Welter ML, Vidal SF, Galanaud D, Derrey S, Dormont D, Cornu P, Yelnik J, Karachi C. Thalamic stimulation for tremor: can target determination be improved? Mov Disord. 2011 Feb 1;26(2):307-12. doi: 10.1002/mds.23448. Epub 2010 Dec 13.

  PMID: 21412838 BACKGROUND

• Wintermark M, Druzgal J, Huss DS, Khaled MA, Monteith S, Raghavan P, Huerta T, Schweickert LC, Burkholder B, Loomba JJ, Zadicario E, Qiao Y, Shah B, Snell J, Eames M, Frysinger R, Kassell N, Elias WJ. Imaging findings in MR imaging-guided focused ultrasound treatment for patients with essential tremor. AJNR Am J Neuroradiol. 2014 May;35(5):891-6. doi: 10.3174/ajnr.A3808. Epub 2013 Dec 26.

  PMID: 24371027 BACKGROUND

MeSH Terms

Conditions

Essential Tremor

Condition Hierarchy (Ancestors)

Movement Disorders; Central Nervous System Diseases; Nervous System Diseases

Study Officials

• Nadya Pyatigorskaya, MD

  Assistance Publique - Hôpitaux de Paris

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 29, 2019
• First Posted: August 29, 2019
• Study Start: January 7, 2020
• Primary Completion: January 10, 2023
• Study Completion: October 4, 2024
• Last Updated: January 25, 2024

Record last verified: 2023-02

Locations

FR (1)