Evaluation of Bilateral Gamma Knife Thalamotomy in Patients Presenting With Severe Essential Tremor (VIMBIL)

Essential tremor (ET) is the most frequent movement disorder. Its prevalence is about 1/200 implying that at least 300 000 peoples are concerned in France. Its frequency increase with age (14% of patients 65 yo). The diagnostic criteria are postural and kinetic tremor that can be associated with head/voice tremor. ET induces a social impairment but also difficulties to perform any task requiring dexterity. With time, tremor can be so severe that every activity of daily living is impaired with loss of autonomy.

Treatment such as betablockers, primidone or antiepileptics might have some efficacy at the beginning. But as the severity of the tremor increases, there is lack of efficacy. Deep Brain stimulation (DBS) of the ventral intermediate nucleus (VIM) of the thalamus can be proposed. However, in case of medical or surgical contra-indication, Gamma Knife (GK) radiosurgery thalamotomy can be an alternative option.

Patients will be included with a minimum of 12 months after having the first thalamotomy (Gamma Knife 1) (done on the most annoying side) subject to no significant deterioration in cognitive assessment, voice assessment and balance and postural assessment or neuroradiological abnormality.

Patients will be assessed with Magnetic resonance imaging (MRI) cerebral, clinical assessment (tremor rating scale) impairment of activity of daily living, neuropsychological evaluation, voice assessment and balance and postural assessment.

The second thalamotomy (Gamma Knife 2) will be proposed and a monitoring at M6 and M12 will be done.

This study will demonstrate the feasibility and tolerance of bilateral GK radiosurgery thalamotomy in ET patients with severe impairment.

Study Overview

• Status: Completed
• Conditions: Patients With Parkinson's Disease
• Intervention / Treatment: Device: Gamma Knife® radiosurgery bilateral

• Study Type: Interventional
• Enrollment (Actual): 33
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Jean REGIS, PUPH; Phone Number: 0691387058; Email: jregis@ap-hm.fr

Study Locations

• France
  • Marseille, France, 13354
    • Assistance Publique Hopitaux de Marseille

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 85 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Patients with essential tremor defined criteria Consensus statement of the movement Disorder Society on Classical Essential Tremor (1998), with trembling of the upper limbs causing functional impairment justifying surgical therapy.
• Man or woman aged 20 to 85 years.
• Patient having an absolute contraindication against or on Deep Brain Stimulation (DBS) of the VIM.
• Patient who received a first effective unilateral thalamotomy on tremor with a satisfactory clinical outcome (no cognitive impairment, lack of postural disorder Musculoskeletal severe lack of dysarthria). The first effective thalamotomy will be characterized by an improved score of tremor ≥ 45% and improved functional gene ≥ 50%.
• Patient who received a first unilateral thalamotomy with satisfactory radiological evolution. Unsatisfactory radiological evolution will be characterized by a contrast uptake> 350 mm3 one year with edema on T2 and Flair sequences extended beyond the internal capsule.
• Patient requiring contralateral treatment because of the severity of the tremor and functional impairment.
• Patient affiliated to a social protection scheme.
• Patient who understood and signed the informed consent form (signature of a third person possible when the patient is unable to read and / or write but in a state to give consent).

Exclusion Criteria:

• Patient with against-indication for performing a brain MRI (pacemaker, intracranial metallic objects etc.)
• Patient with an against-indication to radiosurgical treatment (prior treatment with cerebral radiotherapy)
• Pregnant or lactating women

• Women of childbearing potential unless

  1. surgical sterilization
  2. use of effective contraception (intrauterine device or method more hormonal barrier method), and requiring to present a test pregnancy by assaying the negative serum with chorionic gonadotrope hormon (CGH) when selecting and accept to remain under the current form of contraception for the duration of the study (in women past menopause should be amenorrheic for at least 12 months to be considered as no longer able to bear a child).
• simultaneous participation in another clinical trial or exclusion period of a previous clinical trial.
• vulnerable persons: minors, protected adults (guardianship) and Major unable to consent.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: bilateral thalamotomy radiosurgery; Gamma Knife radiosurgery bilateral	Device: Gamma Knife® radiosurgery bilateral

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
evaluation of cognitive tolerance	Define therapeutic technique "acceptable" in cognitive tolerance level by the Mini Mental State scale (MMS), 10% of subjects decrease their MMS over 2 points.	36 months

Collaborators and Investigators

• Sponsor: Assistance Publique Hopitaux De Marseille
• Investigators: Principal Investigator: Jean REGIS, PUPH, Assistance Publique Hopitaux de Marseille

Study record dates

Study Major Dates

• Study Start (Actual): June 3, 2014
• Primary Completion (Actual): April 16, 2021
• Study Completion (Actual): April 4, 2023

Study Registration Dates

• First Submitted: July 6, 2016
• First Submitted That Met QC Criteria: July 8, 2016
• First Posted (Estimate): July 11, 2016

Study Record Updates

• Last Update Posted (Actual): April 14, 2023
• Last Update Submitted That Met QC Criteria: April 12, 2023
• Last Verified: March 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Parkinsonian Disorders; Basal Ganglia Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases; Parkinson Disease; Essential Tremor
• Other Study ID Numbers: 2013-38 (Other Identifier: APHM); 2013-A01289-36 (Other Identifier: IDRCB)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO