Clinical trial NCT01817088: Sub-thalamic Nucleus Stimulation in Parkinson Disease
Official title: Sub-thalamic Nucleus Stimulation in Parkinson Disease: Comparison of a Two-steps Electrophysiological Approach Under Local and General Anesthesia and a One-step Approach Under General Anesthesia
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Parkinson's Disease
Keywords: Deep Brain Stimulation (DBS)
Parkinson disease
Stereotaxis Technique
Subthalamic nucleus
Lead sponsor: University Hospital, Bordeaux
Sponsor class: OTHER
First posted: 2013-03-22
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: OTHER

Brief summary: Deep brain stimulation (DBS) is an established procedure for the symptomatic treatment of Parkinson's disease. This procedure performed in two steps using electrophysiology. This study is a prospective, randomized and monocentric study to compare two DBS procedures with or without electrophysiology.

A better control of targeting and trajectory is necessary before not using electrophysiology, which is the reference procedure. A new definition of sub thalamic nuclei with new MRI stereotactic landmarks, the use of surgical robot (Neuromata Renishaw) and the use of operative imaging (O-arm) could allow the implantation of electrode in sub-thalamic nuclei without the need of electrophysiology.

Two groups of patients will be followed: a first group of patients with a procedure under general anesthesia alone without electrophysiological stimulation and a second smaller group of patients with a first step of electrode implantation under awake surgery with electrophysiological stimulation followed by a second step under general anesthesia for the implantation of stimulator.

Clinical results will be assessed at 6 months after implantation.

Detailed description: Deep brain stimulation (DBS) is an established procedure for the symptomatic treatment of Parkinson's disease. This procedure performed in two steps using electrophysiology (Limousin et al., 1995) to register the activity of the sub-thalamic nucleus and test the efficacy of stimulation while the patient is awake. A second procedure is needed a few days later to implant the stimulation device under general anaesthesia. The duration of the first procedure is long because of a necessary time of deep stimulation to control the target before definitive implantation. Firstly, the long time of procedure causes pain for the patient. Secondly, the time of procedure, and thus of electrophysiology, is correlated with a rate of device infection of 5 % - 6 % (Hamani et al., 2006; Kenney et al., 2007; Sillay et al., 2008; Doshi et al., 2011). Thirdly, the introduction of several microelectrodes increases the risk of operative and postoperative haemorrhages, estimated at 1 % (Kenney et al., 2007; Sansur et al., 2007; Voges et al., 2007; Bhatia et al., 2008). Moreover, Foltynie et al. (2011) described 12/79 patients treated under general anaesthesia alone with the same post operative results than those who were firstly treated under local anaesthesia.

A better control of targeting and trajectory is necessary before not using electrophysiology, which is the reference procedure. A new definition of sub thalamic nuclei with new MRI stereotactic landmarks, the use of surgical robot (Neuromata Renishaw) and the use of operative imaging (O-arm) could allow the implantation of electrode in sub-thalamic nuclei without the need of electrophysiology. (Caire et al. 2012, In press).

This study is a prospective, randomized and monocentric study. The randomization will be made according to a ratio 2:1 in favour of the technique without electrophysiology. Two groups of patients will be followed: a first group of patients with a procedure under general anesthesia alone without electrophysiological stimulation and a second smaller group of patients with a first step of electrode implantation under awake surgery with electrophysiological stimulation followed by a second step under general anesthesia.

After a preoperative assessment, a end-point evaluation at 6 months after implantation will complete the follow-up.

The stimulation efficacy (UPDRS-3) and the post operative adverse effects will be noticed.

This study will also evaluate the occurrence of a post-traumatic stress disorder (PTSD) in Parkinson disease patients operated under deep brain stimulation.

Eligibility criteria: Inclusion Criteria:

* Age : between 18 and 70 years old
* Parkinson disease in fluctuation state despite the use of an optimal medical treatment
* Dopa sensibility higher than 50% with the L-DOPA test
* Normal MRI
* Mattis Scale \> 130
* Surgical indication approved by a multidisciplinary team
* Patient covered by a social insurance
* Informed consent signed by patient and investigator

Exclusion Criteria:

* Patients with surgical or anesthetic contraindications
* Cerebral atrophy or signal abnormalities on MRI
* Severe Depressive State : The Beck Scale score \> 15
* Women of childbearing potential without efficient contraceptive mean
* Need of long-term antithrombotic treatment

Primary outcomes:
measure: the ratio of preoperative and postoperative UPDRS 3 score
timeFrame: 6 month
Secondary outcomes:
measure: Stimulation efficacy
timeFrame: 6 month
measure: The variance of improvement mean for the "high precision" technique
timeFrame: 6 month
measure: Percentage of patients with an improvement of UPDRS III score
timeFrame: 6 month
measure: The Calculated preoperative and post operative (6 months) equivalent dose of L-DOPA and the decrease of between preoperative and post operative period (6 months).
timeFrame: 6 month
measure: Percentage of patients with failure of the new surgical technique defined with an improvement of less than 35 % with the UPDRS 3 score and an electrode located more than 4 mm from the target
timeFrame: 6 month
measure: Quality of Life
timeFrame: 6 month
measure: Non motor items of UPDRS score in the high precision technique under general anesthesia alone
timeFrame: 6 month
measure: Adverse effects and complications
timeFrame: 6 month
measure: Percentage of improvement in patients with the reference technique
timeFrame: 6 month
measure: Compare the technical feasibility for both surgeries based on the number of electrodes implanted in the target
timeFrame: after surgery
measure: Operative and postoperative surgical adverse effects.
timeFrame: 6 month
measure: Evaluate the influence of two operative procedures on the onset and maintenance of post-operative PTSD
timeFrame: 6 month
measure: Evaluate the influence of two operative procedures on the level of preoperative anxiety and the time course of this anxiety
timeFrame: 1, 3 and 6 month
measure: Differentiate thymic and cognitive factors potentially predictors of the occurrence of post-surgical PTSD
timeFrame: 6 month
measure: Evaluate the long-term effects of the two operating procedures on thymic and cognitive state
timeFrame: 6 month
measure: Evaluate the dose of irradiation received by patients during surgery in both procedures
timeFrame: During surgery
Other outcomes:
Locations:
city: Bordeaux
country: France
facility: University Hospital
Study officials:
affiliation: University Hospital Bordeaux, France
name: Emmanuel CUNY, MD-PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: University Hospital Bordeaux, France
name: Antoine BENARD, MD
role: STUDY_CHAIR
References:
citation: Bronstein JM, Tagliati M, Alterman RL, Lozano AM, Volkmann J, Stefani A, Horak FB, Okun MS, Foote KD, Krack P, Pahwa R, Henderson JM, Hariz MI, Bakay RA, Rezai A, Marks WJ Jr, Moro E, Vitek JL, Weaver FM, Gross RE, DeLong MR. Deep brain stimulation for Parkinson disease: an expert consensus and review of key issues. Arch Neurol. 2011 Feb;68(2):165. doi: 10.1001/archneurol.2010.260. Epub 2010 Oct 11.
citation: Cuny E, Guehl D, Burbaud P, Gross C, Dousset V, Rougier A. Lack of agreement between direct magnetic resonance imaging and statistical determination of a subthalamic target: the role of electrophysiological guidance. J Neurosurg. 2002 Sep;97(3):591-7. doi: 10.3171/jns.2002.97.3.0591.
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citation: Limousin P, Krack P, Pollak P, Benazzouz A, Ardouin C, Hoffmann D, Benabid AL. Electrical stimulation of the subthalamic nucleus in advanced Parkinson's disease. N Engl J Med. 1998 Oct 15;339(16):1105-11. doi: 10.1056/NEJM199810153391603.
citation: Maltete D, Navarro S, Welter ML, Roche S, Bonnet AM, Houeto JL, Mesnage V, Pidoux B, Dormont D, Cornu P, Agid Y. Subthalamic stimulation in Parkinson disease: with or without anesthesia? Arch Neurol. 2004 Mar;61(3):390-2. doi: 10.1001/archneur.61.3.390.
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