Parkinson DiseaseEEGDBSNAdNCT01796483
EEG and Pharmacological Exploration of Executive Dysfunctions Induced by STN-DBS in PD
A study testing Clonidine (Catapressan) in people with Parkinson Disease, run by Hospices Civils de Lyon at 1 site in France.
Trial 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… Read more about this study
- Who is it for?
- Ages 40 to 70 yearsHealthy volunteers can take part
- Conditions the study is for
- Parkinson Disease
- What is being tested?
- Clonidine (Catapressan)
- Type of treatment
- Pill or oral medicine, Medical device
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 37 participants
- Where
- 1 siteFrance
- Study dates
- Oct 2012to Jun 2016
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 40 to 70 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- 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:
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- 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
Who cannot join
- 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.
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- 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
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Exploration électroencéphalographie et Pharmacologique Des Dysfonctionnements exécutifs Induits Par la Stimulation cérébrale Profonde du Noyau Sous-thalamique Dans la Maladie de Parkinson
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.
- Conditions
- Parkinson Disease
- Being tested
- Clonidine (Catapressan), Placebo 90 minutes before EEG
- Keywords
- Parkinson disease, STN-DBS, Impulsivity, Akinesia, Noradrenergic, system
- Medical subject headings
- Parkinson Disease, Impulsive Behavior
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Clonidine (Catapressan)Device
Clonidine (Catapressan) : Oral administration - Single dose (150 µg) - 90 minutes before EEG
Placebo 90 minutes before EEGDevice
Placebo : Oral administration - Single dose (lactose) - 90 minutes before EEG
| Study group | Role | What they receive |
|---|---|---|
| healthy Volunteers | Active comparator | Not described Receives: Device: Clonidine (Catapressan); Device: Placebo 90 minutes before EEG |
| Patients | Experimental | Not described Receives: Device: Clonidine (Catapressan); Device: Placebo 90 minutes before EEG |
What is being measured
The primary outcome is the main question the study is designed to answer.
comparision placebo vs Clonidine
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
Measured: 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.
Secondary outcomes (1)
Localisation of the sources of activity
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)
Measured: 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.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Feb 2013 (estimated)
- Study startOct 2012
- Primary completionJun 2013
- Study completionJun 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Parkinson DiseaseStudies of the same condition, open and under way.
- More trials run by Hospices Civils de LyonThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 37 participants (actual)
Sponsor and investigators
- Lead sponsor
- Hospices Civils de Lyon
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01796483
- Sponsor's protocol ID
- 2012.712
- Acronym
- EEGDBSNAd
- Status last verified
- Jul 2016
- First submitted
- 13 Feb 2013
- Last updated
- 28 May 2019
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Spay C, Albares M, Lio G, Thobois S, Broussolle E, Lau B, Ballanger B, Boulinguez P. Clonidine modulates the activity of the subthalamic-supplementary motor loop: evidence from a pharmacological study combining deep brain stimulation and electroencephalography recordings in Parkinsonian patients. J Neurochem. 2018 Aug;146(3):333-347. doi: 10.1111/jnc.14447.
PubMed 29675956
Study at a glance
From the registry record, last updated by the sponsor on 28 May 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Exploration électroencéphalographie et Pharmacologique Des Dysfonctionnements exécutifs Induits Par la Stimulation cérébrale Profonde du Noyau Sous-thalamique Dans la Maladie de Parkinson
- ClinicalTrials.gov ID
- NCT01796483
- Acronym / sponsor ID
- EEGDBSNAd / 2012.712
- Conditions
- Parkinson Disease
- Keywords
- Parkinson disease, STN-DBS, Impulsivity, Akinesia, Noradrenergic, system
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 37 participants (actual)
- Lead sponsor
- Hospices Civils de LyonUniversity, hospital or other
- Study start
- Oct 2012
- Primary completion
- Jun 2013 (actual)
- Study completion
- Jun 2016 (actual)
- First posted
- 21 Feb 2013 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| healthy Volunteers | Active comparator | Device: Clonidine (Catapressan), Device: Placebo 90 minutes before EEG |
| Patients | Experimental | Device: Clonidine (Catapressan), Device: Placebo 90 minutes before EEG |
Who may qualify
- Ages
- 40 to 70 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (20 listed)
- For all right-handed participants :
- 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;
- Without a history of neurologic or psychiatric disease
Key exclusion criteria (14 listed)
- For all the participants:
- 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.
- Already participating to another biomedical research;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Clonidine (Catapressan)Clonidine (Catapressan) : Oral administration - Single dose (150 µg) - 90 minutes before EEG | Device | Patients, healthy Volunteers |
| Placebo 90 minutes before EEGPlacebo : Oral administration - Single dose (lactose) - 90 minutes before EEG | Device | Patients, healthy Volunteers |
Primary outcome
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
1 secondary outcome
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.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 May 2019.
- Results publication: PubMed 29675956Spay C, Albares M, Lio G, Thobois S, Broussolle E, Lau B, Ballanger B, Boulinguez P. Clonidine modulates the activity of the subthalamic-supplementary motor loop: evidence from a pharmacological study combining deep brain stimulation and electroencephalography recordings in Parkinsonian patients. J Neurochem. 2018 Aug;146(3):333-347. doi: 10.1111/jnc.14447.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Clonidine (Catapressan) in people with Parkinson Disease, run by Hospices Civils de Lyon at 1 site in France.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 20 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 28 May 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01796483, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 May 2019.