Thalamic LFPs and VIM DBS in Essential Tremor: Correlation, Evolution, and Therapeutic Perspectives

Essential Tremor Clinical Trial

— VIM-CLT  

Official title:

Thalamic LFPs and VIM DBS in Essential Tremor: Correlation, Evolution, and Therapeutic Perspectives

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02264925
• Other study ID #: CHUBX 2013/15
• Status: Completed
• Phase: N/A
• Start date: November 2014
• Est. completion date: November 19, 2020

Study information

• Verified date: August 2021
• Source: University Hospital, Bordeaux
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 12
• Est. completion date: November 19, 2020
• Est. primary completion date: November 19, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

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)

Related Conditions & MeSH terms

• Essential Tremor
• Tremor

Intervention

Device:
• Deep Brain Stimulation with Medtronic Activa PC+S systems
Deep Brain Stimulation of VIM.

Locations

Country	Name	City	State
France	University Hospital Bordeaux, France	Bordeaux

Sponsors (2)

Lead Sponsor	Collaborator
University Hospital, Bordeaux	APTES 100 rue boileau 69006 Lyon

Country where clinical trial is conducted

France, 

References & Publications (10)

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. — View 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. — View 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. — View 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. Epub 2005 Jul 18. Review. — View Citation

Garcia Ruiz P, Muñiz de Igneson J, Lopez Ferro O, Martin C, Magariños Ascone C. Deep brain stimulation holidays in essential tremor. J Neurol. 2001 Aug;248(8):725-6. — View 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. — View 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. — View 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. — View 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. — View 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	3 month after implantation
Primary	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	12 month after implantation