Evaluation of the Predictors of Clinical and Radiological Response to Gamma-Knife Radiosurgery in the Treatment of Intermediate Ventral Nucleus of the Thalamus (VIM) Thalamotomy Tremor. (GARP)

Gamma-Knife radiosurgery of the VIM for patients presenting with severe drug-resistant tremor is now current practice as an alternative to Deep Brain Stimulation (DBS) of the VIM.

Now, around 100 patients are treated annually in our unit (essential tremor or Parkinson tremor).

Clinical and radiological follow-up is demonstrating that 80% of these patients are presenting with a homogenous response complete or subtotal, the disappearance of the tremor mean delay of 6 months after radiosurgery. In neuroradiological responses on the MRI, is appearing roughly at the same time local contrast enhancement surrounding highty to signal no associated with clinical side effects.

In 15 to 20% of the patients, the clinical effets is not obtained and in the vast majority no MRI response or minimal MRI response is observed on images suggesting that these failures are related to specific resistance to radiosurgery of this subgroup.

In roughly 5% of the patients, at the contrary, hyper response is observe on the MRI rating clinically with side effects (hemiparesis or proprioceptive ataxia or dysarthria, hands problems….). The adverse effects are generally reversible either in whole or in part with the resorption of the perilesionnel oedema.

It would be extremely helpfull to be able to identify in advance these 2 groups of hyper and hypo respondeurs.

The capacity to identify in advance these patients at risk to hypo or hyper response would allow us to either contre-indicate radiosurgery or modify radiosurgery technicaly at the time of dose planing.

Sequently, these predictions would allow us to tailor individually mission management and information leading to improvment of the efficacy and tolerance of this kind of intervention.

The parameters suspected to be likely to influence the response are :

• genetics
• co-morbidities (diabetis, vascular…)
• Main aspect of the brain (severe atrophy, vascular, micro-infacts…)
• Chronobiological (timing during the day of the radiosurgical procedure)
• Associated medication (potential radioprotector or radiosensitizer effect of some drugs)
• Radiobiological (dose rate…)

The goal of this study is to collect all of these informations out of genetical one in the cohort of 700 patients having benefited ou will benefit from radiosurgery in the situation for essential tremor and parkinson disease. It will be test the predictive value of these parameters and the capacity to predict hyper or hypo response.

The work on the genetic material will take place in the second stage in the frame of a new different resarch project.

Study Overview

• Status: Unknown
• Conditions: Severe Disabling Tremor
• Intervention / Treatment: Device: gamma knife radiosurgery

• Study Type: Observational
• Enrollment (Anticipated): 700

Contacts and Locations

• Study Contact: Name: Jean REGIS, PU-PH; Phone Number: +33 491387058; Email: jregis@ap-hm.fr

Study Locations

• France
  • Marseille, France, 13354
    • Recruiting
    • Assistance Publique Hopitaux de Marseille
    • Contact: Jean REGIS, PU-PH; Phone Number: +33 491387056; Email: jregis@ap-hm.fr
    • Principal Investigator: Jean REGIS, PU-PH

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

Patients with severe tremor (Essential Tremor type, Parkinson's disease tremor or others) responsible for significant functional impairment.

Description

Inclusion Criteria:

• Male or female aged 20 years minimum
• Patient with absolute contraindication or relative to deep brain stimulation (DBS) of VIM.
• Patient having the Gamma Knife radiosurgery of VIM (combining clinical and paraclinical conditions).
• Patient affiliated to a social security scheme.
• Patient having understood and signed the information notice for non opposition.

Exclusion Criteria:

• Patient having a contraindication to performing a cerebral MRI (pace-maker, intracerebral metallic object etc.)
• Patient with a contraindication to radiosurgical treatment (previous treatment with cerebral radiotherapy)
• Vulnerable persons: minors, protected adults (guardianship or trusteeship) and adults unable to express their non-opposition.

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Patients treated with gamma knife radiosurgery; Collection of non-genetic, chronobiological, therapeutic and co-morbidities	Device: gamma knife radiosurgery; The surgical procedure consists of a very partial radiation of the brain with a stereotactic precision performed in current practice

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinical evaluation of tremor reduction in relation to clinical co-morbidity	Clinical response increases with decrease in clinical co-morbidity	12 months

Collaborators and Investigators

• Sponsor: Assistance Publique Hopitaux De Marseille
• Investigators: Study Director: Jean-Olivier ARNAUD, General Director, Assistance Publique Hopitaux de Marseille

Study record dates

Study Major Dates

• Study Start (Actual): October 23, 2017
• Primary Completion (Anticipated): October 22, 2021
• Study Completion (Anticipated): October 22, 2021

Study Registration Dates

• First Submitted: November 16, 2017
• First Submitted That Met QC Criteria: November 20, 2017
• First Posted (Actual): November 22, 2017

Study Record Updates

• Last Update Posted (Actual): November 22, 2017
• Last Update Submitted That Met QC Criteria: November 20, 2017
• Last Verified: November 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Nervous System Diseases; Neurologic Manifestations; Dyskinesias; Tremor
• Other Study ID Numbers: 2017-09; Id RCB (Registry Identifier: 2018-A00771-54)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No