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EEG and Pharmacological Exploration of Executive Dysfunctions Induced by STN-DBS in PD (EEGDBSNAd)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01796483
Recruitment Status : Completed
First Posted : February 21, 2013
Last Update Posted : May 28, 2019
Sponsor:
Information provided by (Responsible Party):
Hospices Civils de Lyon

Brief Summary:

Deep brain stimulation (DBS) of the subthalamic nucleus (STN) remarkably improves motor functions in patients with Parkinson disease (PD). However, growing evidence suggests that STN-DBS also causes executive inhibitory deficits and impulsive behaviour (Jahanshahi et al 2000; Schroeder et al 2002; Hershey et al 2004; Thobois et al 2007; Frank et al 2007; Ballanger et al., 2009). Despite a widespread use, the mechanisms of action of STN-DBS are still unclear. Two reasons might explain this. 1) From a theoretical point of view, cognitive models of executive control mechanisms are incomplete. 2) From a methodological point of view, investigating cerebral activity during STN-DBS is very limited because most techniques are incompatible with locally implanted electrodes.

This project relies on a double opportunity to answer these questions offered by recent theoretical and methodological advances. First, investigations in healthy subjects (Jaffard et al 2007, 2008, Boulinguez et al 2009) revealed an essential function of inhibitory control, so far ignored, consisting in locking in advance movement triggering processes to prevent undesired automatic or anticipated responses to unattended stimuli. In other words, key processes of executive control may act tonically before stimulation occurs, calling brain imaging studies to look at proactive and not only reactive activations. Second, recent advances in EEG signal processing now allow suppressing from the electroencephalogram DBS-related artifacts (Allen et al. 2010), providing a tremendous opportunity to use a non-invasive technique with the high temporal resolution necessary to disentangle proactive from reactive brain activity. To our knowledge, up to date no study has been published using EEG with STN-DBS patients since Allen et al.'s paper. The first operational purpose of this project is to identify the anatomo-functional origin of STN-DBS-induced executive dysfunction using EEG recordings in classical stimulus-response tasks. Results expected from this first part of the project may help resolving other long-lasting issues. Indeed, reactivity as assessed by simple reaction time in non-implanted patients as well as impulsivity in STN-DBS patients are known to remain insensitive to dopaminergic medication. Since the proactive activity related to executive, inhibitory, control may be supported by the noradrenergic (NA) system, the second purpose of this project is to test the original hypothesis according to which NA plays a central role in both akinesia and STN-DBS side effects.


Condition or disease Intervention/treatment Phase
Parkinson Disease Device: Clonidine (Catapressan) Device: Placebo 90 minutes before EEG Not Applicable

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 37 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Basic Science
Official Title: Exploration électroencéphalographie et Pharmacologique Des Dysfonctionnements exécutifs Induits Par la Stimulation cérébrale Profonde du Noyau Sous-thalamique Dans la Maladie de Parkinson
Study Start Date : October 2012
Actual Primary Completion Date : June 2013
Actual Study Completion Date : June 2016

Resource links provided by the National Library of Medicine

Drug Information available for: Clonidine

Arm Intervention/treatment
Active Comparator: healthy Volunteers Device: Clonidine (Catapressan)
Clonidine (Catapressan) : Oral administration - Single dose (150 µg) - 90 minutes before EEG

Device: Placebo 90 minutes before EEG
Placebo : Oral administration - Single dose (lactose) - 90 minutes before EEG

Experimental: Patients Device: Clonidine (Catapressan)
Clonidine (Catapressan) : Oral administration - Single dose (150 µg) - 90 minutes before EEG

Device: Placebo 90 minutes before EEG
Placebo : Oral administration - Single dose (lactose) - 90 minutes before EEG




Primary Outcome Measures :
  1. comparision placebo vs Clonidine [ Time Frame: Primary outcome data will be analyzed at the completion of the study, i.e. after the planned 18-month duration of data collection from patients and control subjects. ]
    The primary outcome the study was designed to compare placebo vs clonidine effects on STN-DBS modulations of proactive inhibitory control using commission error rate as an index of impulsivity and reaction time as an index of akinesia


Secondary Outcome Measures :
  1. Localisation of the sources of activity [ Time Frame: Secondary outcome data will be analyzed at the completion of the study, i.e. after the planned 18-month duration of data collection from patients and control subjects. ]
    The secondary outcome the study was designed to localize the sources of activity using EEG predicted by the proactive model and accounting for reaction time in controls and non impulsive patients ON stimulation (placebo session)


Other Outcome Measures:
  1. Identification of the neural bases of efficient Brain activity regulation [ Time Frame: this outcome measure will be analyzed at the completion of the study, i.e. after the planned 18-month duration of data collection from patients and control subjects. ]
    The secondary outcome the study was designed to identify the neural bases of efficient brain activity regulation by STN-DBS in non impulsive PD patients (ON vs OFF comparison - placebo session)

  2. Identification of source showing abnormal activity [ Time Frame: this outcome mesaure will be analyzed at the completion of the study, i.e. after the planned 18-month duration of data collection from patients and control subjects. ]
    The secondary outcome the study was designed to detect among the sources revealed above those which show abnormal activity in impulsive PD patients ON stimulation

  3. Identification of the source modulated by Clonidine [ Time Frame: this outcome mesaure will be analyzed at the completion of the study, i.e. after the planned 18-month duration of data collection from patients and control subjects. ]
    the study was designed to detect among the sources revealed above which ones are modulated by the pharmacological manipulation (Placebo vs Clonidine)



Information from the National Library of Medicine

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Ages Eligible for Study:   40 Years to 70 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • For all right-handed participants :

    • Age between ≥ 40 and ≤ 70 years old ;
    • Weight between 45 and 95 kg
    • Without cognitive deterioration (MATTIS score > 130) ;
    • Without orthostatic hypotension known;
    • Showing no contraindication to clonidine:

      • Hypersensibility known to clonidine or to an excipient of Catapressan
      • Depressed state
      • Severe bradyarrythmias due to a sinus node disease or atrioventricular block ventricular second or third degree ;
      • Treatment by sultopride;
    • Showing no contraindication to the placebo of clonidine : lactose intolerance;
    • Affiliated to a social security scheme or assimilated;
    • Not being the subject of a measure of legal protection;
    • Having consented to participate in the study and written inform consent.

Specific to right-handed parkinsonian patients :

  • Having an idiopathic Parkinson's disease Dopa-sensitive;
  • Treated with deep brain stimulation of the subthalamic nucleus since at least 3 months;
  • With stable antiparkinsonian treatment for at least 2 months and that it will be possible not to modified during the entire experiment;

Specific to right-handed healthy controls :

• Without a history of neurologic or psychiatric disease

Exclusion Criteria:

  • For all the participants:

    • Having somatic medication treatment with a cerebral or psychic impact;
    • Presenting dependence and abuse to cannabis or to other addictive substance according to the DSM-IV-TR, with the exception of tobacco;
    • Already participating to another biomedical research except surgical project involving a new material of deep brain stimulation because in this case stimulation parameters and patients benefiting of it will be the same;
    • Pregnant or breastfeeding women (diagnostic examination);
    • Subjects having, after reading questionnaires or after the medical examination, contraindication to EEG exam or to clonidine.

Specific to parkinsonian patients:

  • Having other neurologic or psychiatric associated pathology, notably depression;
  • Already participating to another biomedical research except surgical project involving a new material of deep brain stimulation because in this case stimulation parameters and patients benefiting of it will be the same;
  • Pregnant or breastfeeding women (diagnostic examination); Subjects having, after reading questionnaires or after the medical examination, contraindication to EEG exam or to clonidine.

Specific to healthy subjects :

  • Already participating to another biomedical research;
  • Subjects who exceeded the annual compensation allowed for participation in research protocols;
  • Subjects with an inability to understand or carry out the study (language barrier, mental disability, obvious lack of motivation…) judged by the investigator

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01796483


Locations
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France
Hospices Civils de Lyon Hôpital Pierre Wertheimer
Bron, France, 69677
Sponsors and Collaborators
Hospices Civils de Lyon
Publications of Results:
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Responsible Party: Hospices Civils de Lyon
ClinicalTrials.gov Identifier: NCT01796483    
Other Study ID Numbers: 2012.712
First Posted: February 21, 2013    Key Record Dates
Last Update Posted: May 28, 2019
Last Verified: July 2016
Keywords provided by Hospices Civils de Lyon:
Parkinson disease
STN-DBS
Impulsivity
Akinesia
Noradrenergic
system
Additional relevant MeSH terms:
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Parkinson Disease
Parkinsonian Disorders
Basal Ganglia Diseases
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Movement Disorders
Neurodegenerative Diseases
Synucleinopathies
Clonidine
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Antihypertensive Agents
Sympatholytics
Autonomic Agents
Adrenergic alpha-2 Receptor Agonists
Adrenergic alpha-Agonists
Adrenergic Agonists
Adrenergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action