Thalamic LFPs and VIM DBS in Essential Tremor: Correlation, Evolution, and Therapeutic Perspectives (VIM-CLT)
Primary Purpose
Essential Tremor
Status
Completed
Phase
Not Applicable
Locations
France
Study Type
Interventional
Intervention
Deep Brain Stimulation with Medtronic Activa PC+S systems
Sponsored by
About this trial
This is an interventional treatment trial for Essential Tremor focused on measuring Essential tremor, Deep brain stimulation (DBS), Ventral intermediate Thalamus (VIM), Local field potentials (LFPs), Closed loop therapy
Eligibility Criteria
Inclusion Criteria:
- Patients suffering from severe and disabling ET with serious impact on their quality of life (QoL).
- 18-70 years old
- Free of evolutive and untreated psychiatric disorder
- Tremor must be predominant in the upper limbs although it can affect the lower limbs, head and voice.
- Affiliation to a social security system
- Written informed consent signed by the participant and the investigator (prior to any examination required by research)
Exclusion Criteria:
- Parkinsonian tremor
- Pregnancy or lactating women
- Severe co-morbidity (cardiac, renal or respiratory failures, evolutive cancer)
- Impaired cognitive functions (score <130 on Mattis scale).
- Patients with severe atrophy or lesions on MRI
- Depression (Beck > 10)
- Participation in another clinical research for 18 months (after surgery)
Sites / Locations
- University Hospital Bordeaux, France
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Deep Brain Stimulation
Arm Description
All of included patients will receive a standard deep brain stimulation of the thalamus in order to reduce their essential tremor
Outcomes
Primary Outcome Measures
LFPs records 3 month after implantation
in order to characterize the features of tremor-related thalamic activity during the initiation of movement-related tremor-induced activity
LFPs records 12 month after implantation
in order to characterize the features of tremor-related thalamic activity during the initiation of movement-related tremor-induced activity
Secondary Outcome Measures
Full Information
NCT ID
NCT02264925
First Posted
June 20, 2014
Last Updated
August 6, 2021
Sponsor
University Hospital, Bordeaux
Collaborators
APTES 100 rue boileau 69006 Lyon
1. Study Identification
Unique Protocol Identification Number
NCT02264925
Brief Title
Thalamic LFPs and VIM DBS in Essential Tremor: Correlation, Evolution, and Therapeutic Perspectives
Acronym
VIM-CLT
Official Title
Thalamic LFPs and VIM DBS in Essential Tremor: Correlation, Evolution, and Therapeutic Perspectives
Study Type
Interventional
2. Study Status
Record Verification Date
August 2021
Overall Recruitment Status
Completed
Study Start Date
November 2014 (Actual)
Primary Completion Date
November 19, 2020 (Actual)
Study Completion Date
November 19, 2020 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University Hospital, Bordeaux
Collaborators
APTES 100 rue boileau 69006 Lyon
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
The objective of this study is to characterize through spectral analysis intra-thalamic local field potentials (LFPs) recorded through implanted DBS leads during periods with and without tremor in patients suffering from severe essential tremor.
Detailed Description
Essential tremor (ET) is one of the most common adult movement disorders with a prevalence of 4% in the general population. Although several medications (primidone, beta-adrenergic blockers, benzodiazepines…) are commonly used, few of them are truly effective for controlling the severe forms of ET. Since 1987, an alternative has emerged with the development of high frequency deep brain stimulation (DBS) of the thalamic nucleus ventralis intermedius (VIM). This surgical technique now represents the gold standard treatment for tremor-disabled ET patients. Although VIM-DBS is clearly effective for treatment of essential tremor (ET) a partial loss of DBS effectiveness may occur over time in some patients. This loss of DBS effectiveness could be related to an adaptation of the local neuronal network to chronic stimulation (changes in synaptic plasticity). In order to avoid this problem, investigators plan to develop a intermittent mode of VIM stimulation using a new Medtronic device combining a DBS system with local field potential (LFPs) sensing capability. First, investigators propose to analyse VIM LFPs in order to define a tremor biomarker in 10 patients operated for severe ET. Thereafter, investigators will automatically detect this biomarker using a specific algorithm and use it to trigger stimulation at the onset of tremor only. Thus, this project will allow us to optimize DBS therapy in ET, by improving the longevity of implantable devices and avoiding the loss of efficacy previously reported
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Essential Tremor
Keywords
Essential tremor, Deep brain stimulation (DBS), Ventral intermediate Thalamus (VIM), Local field potentials (LFPs), Closed loop therapy
7. Study Design
Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
12 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Deep Brain Stimulation
Arm Type
Experimental
Arm Description
All of included patients will receive a standard deep brain stimulation of the thalamus in order to reduce their essential tremor
Intervention Type
Device
Intervention Name(s)
Deep Brain Stimulation with Medtronic Activa PC+S systems
Intervention Description
Deep Brain Stimulation of VIM.
Primary Outcome Measure Information:
Title
LFPs records 3 month after implantation
Description
in order to characterize the features of tremor-related thalamic activity during the initiation of movement-related tremor-induced activity
Time Frame
3 month after implantation
Title
LFPs records 12 month after implantation
Description
in order to characterize the features of tremor-related thalamic activity during the initiation of movement-related tremor-induced activity
Time Frame
12 month after implantation
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Patients suffering from severe and disabling ET with serious impact on their quality of life (QoL).
18-70 years old
Free of evolutive and untreated psychiatric disorder
Tremor must be predominant in the upper limbs although it can affect the lower limbs, head and voice.
Affiliation to a social security system
Written informed consent signed by the participant and the investigator (prior to any examination required by research)
Exclusion Criteria:
Parkinsonian tremor
Pregnancy or lactating women
Severe co-morbidity (cardiac, renal or respiratory failures, evolutive cancer)
Impaired cognitive functions (score <130 on Mattis scale).
Patients with severe atrophy or lesions on MRI
Depression (Beck > 10)
Participation in another clinical research for 18 months (after surgery)
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
BURBAUD Pierre, MD-PhD
Organizational Affiliation
University Hospital Bordeaux, France
Official's Role
Study Director
First Name & Middle Initial & Last Name & Degree
Nicolas LANGBOUR, PhD
Organizational Affiliation
IMN CNRS UMR 5293, Université Bordeaux 2 Segalen
Official's Role
Study Chair
Facility Information:
Facility Name
University Hospital Bordeaux, France
City
Bordeaux
ZIP/Postal Code
33076
Country
France
12. IPD Sharing Statement
Citations:
PubMed Identifier
20927533
Citation
Barbe MT, Liebhart L, Runge M, Pauls KA, Wojtecki L, Schnitzler A, Allert N, Fink GR, Sturm V, Maarouf M, Timmermann L. Deep brain stimulation in the nucleus ventralis intermedius in patients with essential tremor: habituation of tremor suppression. J Neurol. 2011 Mar;258(3):434-9. doi: 10.1007/s00415-010-5773-3. Epub 2010 Oct 8.
Results Reference
background
PubMed Identifier
3329873
Citation
Benabid AL, Pollak P, Louveau A, Henry S, de Rougemont J. Combined (thalamotomy and stimulation) stereotactic surgery of the VIM thalamic nucleus for bilateral Parkinson disease. Appl Neurophysiol. 1987;50(1-6):344-6. doi: 10.1159/000100803.
Results Reference
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PubMed Identifier
17922323
Citation
Blomstedt P, Hariz GM, Hariz MI, Koskinen LO. Thalamic deep brain stimulation in the treatment of essential tremor: a long-term follow-up. Br J Neurosurg. 2007 Oct;21(5):504-9. doi: 10.1080/02688690701552278.
Results Reference
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PubMed Identifier
16029963
Citation
Brown P, Williams D. Basal ganglia local field potential activity: character and functional significance in the human. Clin Neurophysiol. 2005 Nov;116(11):2510-9. doi: 10.1016/j.clinph.2005.05.009. Epub 2005 Jul 18.
Results Reference
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PubMed Identifier
11569910
Citation
Garcia Ruiz P, Muniz de Igneson J, Lopez Ferro O, Martin C, Magarinos Ascone C. Deep brain stimulation holidays in essential tremor. J Neurol. 2001 Aug;248(8):725-6. doi: 10.1007/s004150170127. No abstract available.
Results Reference
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PubMed Identifier
10853080
Citation
Hariz MI, Shamsgovara P, Johansson F, Hariz G, Fodstad H. Tolerance and tremor rebound following long-term chronic thalamic stimulation for Parkinsonian and essential tremor. Stereotact Funct Neurosurg. 1999;72(2-4):208-18. doi: 10.1159/000029728.
Results Reference
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PubMed Identifier
10084526
Citation
Limousin P, Speelman JD, Gielen F, Janssens M. Multicentre European study of thalamic stimulation in parkinsonian and essential tremor. J Neurol Neurosurg Psychiatry. 1999 Mar;66(3):289-96. doi: 10.1136/jnnp.66.3.289.
Results Reference
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PubMed Identifier
10675426
Citation
Schuurman PR, Bosch DA, Bossuyt PM, Bonsel GJ, van Someren EJ, de Bie RM, Merkus MP, Speelman JD. A comparison of continuous thalamic stimulation and thalamotomy for suppression of severe tremor. N Engl J Med. 2000 Feb 17;342(7):461-8. doi: 10.1056/NEJM200002173420703.
Results Reference
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PubMed Identifier
17343274
Citation
Stacy MA, Elble RJ, Ondo WG, Wu SC, Hulihan J; TRS study group. Assessment of interrater and intrarater reliability of the Fahn-Tolosa-Marin Tremor Rating Scale in essential tremor. Mov Disord. 2007 Apr 30;22(6):833-8. doi: 10.1002/mds.21412.
Results Reference
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PubMed Identifier
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Citation
Yoshida F, Martinez-Torres I, Pogosyan A, Holl E, Petersen E, Chen CC, Foltynie T, Limousin P, Zrinzo LU, Hariz MI, Brown P. Value of subthalamic nucleus local field potentials recordings in predicting stimulation parameters for deep brain stimulation in Parkinson's disease. J Neurol Neurosurg Psychiatry. 2010 Aug;81(8):885-9. doi: 10.1136/jnnp.2009.190918. Epub 2010 May 12.
Results Reference
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Thalamic LFPs and VIM DBS in Essential Tremor: Correlation, Evolution, and Therapeutic Perspectives
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