EpilepsyPhase 2/3NCT00228371
STIMEP : Assessment of Subthalamic Nucleus Stimulation in Drug Resistant Epilepsy
A Phase 2/3 study testing Neurostimulation in people with Epilepsy and Drug Resistant, run by University Hospital, Grenoble at 3 sites in France.
Trial summary
The aim of this study is to evaluate the effectiveness and the safety of deep brain stimulation in drug resistant epilepsy. This is a double blind, controlled and randomized clinical trial with two cross-over groups and four phases. Read more about this study
- Who is it for?
- Ages 18 to 50 years
- Conditions the study is for
- Epilepsy, Drug Resistant
- What is being tested?
- Neurostimulation
- Type of treatment
- Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 4 participants
- Where
- 3 sitesFrance
- Study dates
- Sep 2005to Mar 2010
- Phase
- Phase 2/3
- 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 18 to 50 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- Epilepsy resistant to antiepileptic drug and dopaminergic D2 agonist.
- No curative exeresis surgery possible
- Metabolism deficiency of DOPA above 1 DS, evaluated by Positron Emission Tomography (PET) using fluorodopa
- Age ranging from 18 to 50
- capacity to consent
- Affiliation to the French Social Security
Who cannot join
- pregnant woman or nursing mother
- change of antiepileptic, 30 days before base line
- convulsive "etat de mal" that requires an hospitalisation, 30 days before base line
Trial locations and contacts
3 sites in 1 country.
France3 sites
University Hospital of Grenoble
Grenoble, Isere, 38043
University Hospital of Rennes
Rennes, 35000
University Hospital of Strasbourg
Strasbourg, 67091
About this study
Official title: Assessment of Subthalamic Nucleus Stimulation in Drug Resistant Epilepsy Associated With Dopaminergic Metabolism Deficit. A Randomized, Double Blind, Controlled Trial.
The aim of this study is to evaluate the effectiveness and the safety of deep brain stimulation in drug resistant epilepsy.
This is a double blind, controlled and randomized clinical trial with two cross-over groups and four phases.
Read more
Phase 1 : base line, open phase consisting of follow-up of patients with their standard treatment.
Phase 2 : Randomisation, lead implantation, followed by 3 months wash out period with the stimulator switch OFF.
Phase 3 : cross-over, double blind phase : 3 months with stimulator switch ON or OFF depending on randomization allocation, followed by 3 months with the stimulator switch on the opposite position. The placebo consisting of turn OFF the stimulator.
Phase 4 : open phase, one year follow-up of all patients with the stimulator switch ON.
Read the detailed description
The experimental work performed for more than 15 years by several research teams shows in animal models of epilepsy, that several circuits of basal ganglia are involved in the control of epilepsy seizures. The existence of those circuits leads to the possibility of therapeutic applications in particular deep brain stimulation.
Preliminary results (Benabid et al, 2002) (Chabardes et al , 2002) suggest that the neuromodulation of basal ganglia and in particular the subthalamic nucleus and the substantia nigra pars reticulata could have a therapeutic effects in patients with drug resistant epilepsy and no possibility of resection surgery.
This is a double blind, controlled and randomized clinical trial with two cross-over groups and four phases.
Phase 1 : base line, open phase consisting of follow-up of patients with their standard treatment.
Phase 2 : Randomisation, lead implantation, followed by 3 months wash out period with the stimulator switch OFF.
Phase 3 : cross-over, double blind phase : 3 months with stimulator switch ON or OFF depending on randomization allocation, followed by 3 months with the stimulator switch on the opposite position.
Phase 4 : open phase, one year follow-up of all patients with the stimulator switch ON.
There are two differents groups at phase 3 :
- Group A : 10 patients with the stimulator switch ON for three months and switch OFF for the next three months.
- Group B : 10 patients with the opposite sequence, OFF and ON.
Main objective :
- To show that high frequency deep brain stimulation of the subthalamic nucleus decrease the frequency of epileptic seizure compared with no stimulation.
Secondary objectives :
- To show that high frequency deep brain stimulation of the subthalamic nucleus improve the quality of life.
- To describe the side effects of this device and compare with those described in Parkinson patients. In particular to check the onset of dyskinesia related to dopamine.
- To compare the distribution of seizure frequency after stimulation to the base line.
- To show that the number of patients responding to treatment are higher in the group with stimulator switch ON than in the group with the stimulator turn OFF.
- To compare the number of days without seizure with the stimulator switch ON or OFF.
- To evaluated the neuropsychologic effect induced by the neurostimulation
- To quantify the types and the ratio of different seizures during the ON phase and the OFF phase.
- To monitor the secondary drug use during the study.
Control visits : all patients will have a control visit every 4 weeks during the study.
- Conditions
- Epilepsy, Drug Resistant
- Being tested
- Neurostimulation
- Keywords
- Epilepsy, deep brain stimulation, Subthalamic nucleus, Drug resistant epilepsy
- Medical subject headings
- Epilepsy, Drug Resistant Epilepsy
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
NeurostimulationDevice
Also called Neurostimulation of subthalamic nucleus
High frequency neurostimulation of subthalamic nucleus : quadrupolar electrode, type 3389, n° : I7 02 08 39709 158, Medtronic, Minneapolis, USA
| Study group | Role | What they receive |
|---|---|---|
| 1 | Other | The stimulator is switch ON during the first phase of the cross-over and switch OFF during the second phase Receives: Device: Neurostimulation |
| 2 | Other | The stimulator is switch OFF during the first phase of the cross-over and switch ON during the second phase Receives: Device: Neurostimulation |
What is being measured
The primary outcome is the main question the study is designed to answer.
- Daily seizure frequency at each phase
Measured: at each phase
Secondary outcomes (3)
The number of days without seizure during each phase
Measured: at each phase
Quality of life : SEALS, QOLIE-31 and NHP scales
Measured: at each phase
Neuropsychological test : WAIS, GROBER and Busckhe, Wisconsin Card Sorting Test, TRAIL test, LURIA test, Beck Depression Inventory, verbal flow test, empathy test
Measured: at each phase
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Sep 2005 (estimated)
- Study startSep 2005
- Primary completionDec 2009
- Study completionMar 2010
Why it stopped: insufficent enrolement
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (9)Papers the sponsor has linked to this study.
- Other trials for EpilepsyStudies of the same condition, open and under way.
- More trials run by University Hospital, GrenobleThe 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 2/3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 4 participants (actual)
Sponsor and investigators
- Lead sponsor
- University Hospital, Grenoble
- Sponsor type
- University, hospital or other
- Collaborators
- Ministry of Health, France
- Responsible party
- Sponsor
- Investigators
- Stephan CHABARDES, Dr, Principal investigator, University Hospital of Grenoble, Neuro surgery
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00228371
- Sponsor's protocol ID
- DCIC 03 23
- Status last verified
- May 2015
- First submitted
- 26 Sep 2005
- Last updated
- 28 May 2015
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Alexander GE, Crutcher MD. Functional architecture of basal ganglia circuits: neural substrates of parallel processing. Trends Neurosci. 1990 Jul;13(7):266-71. doi: 10.1016/0166-2236(90)90107-l.
PubMed 1695401Ardouin C, Pillon B, Peiffer E, Bejjani P, Limousin P, Damier P, Arnulf I, Benabid AL, Agid Y, Pollak P. Bilateral subthalamic or pallidal stimulation for Parkinson's disease affects neither memory nor executive functions: a consecutive series of 62 patients. Ann Neurol. 1999 Aug;46(2):217-23. doi: 10.1002/1531-8249(199908)46:23.0.co;2-z.
PubMed 10443887Benabid AL, Koudsie A, Benazzouz A, Vercueil L, Fraix V, Chabardes S, Lebas JF, Pollak P. Deep brain stimulation of the corpus luysi (subthalamic nucleus) and other targets in Parkinson's disease. Extension to new indications such as dystonia and epilepsy. J Neurol. 2001 Sep;248 Suppl 3:III37-47. doi: 10.1007/pl00007825.
PubMed 11697687Benabid AL, Minotti L, Koudsie A, de Saint Martin A, Hirsch E. Antiepileptic effect of high-frequency stimulation of the subthalamic nucleus (corpus luysi) in a case of medically intractable epilepsy caused by focal dysplasia: a 30-month follow-up: technical case report. Neurosurgery. 2002 Jun;50(6):1385-91; discussion 1391-2. doi: 10.1097/00006123-200206000-00037.
PubMed 12015863Chabardes S, Kahane P, Minotti L, Koudsie A, Hirsch E, Benabid AL. Deep brain stimulation in epilepsy with particular reference to the subthalamic nucleus. Epileptic Disord. 2002 Dec;4 Suppl 3:S83-93.
PubMed 12495878Chkhenkeli SA, Chkhenkeli IS. Effects of therapeutic stimulation of nucleus caudatus on epileptic electrical activity of brain in patients with intractable epilepsy. Stereotact Funct Neurosurg. 1997;69(1-4 Pt 2):221-4. doi: 10.1159/000099878.
PubMed 9711758Cooper IS, Amin I, Gilman S. The effect of chronic cerebellar stimulation upon epilepsy in man. Trans Am Neurol Assoc. 1973;98:192-6. No abstract available.
PubMed 4206369DeLong MR. Primate models of movement disorders of basal ganglia origin. Trends Neurosci. 1990 Jul;13(7):281-5. doi: 10.1016/0166-2236(90)90110-v.
PubMed 1695404Dematteis M, Kahane P, Vercueil L, Depaulis A. MRI evidence for the involvement of basal ganglia in epileptic seizures: an hypothesis. Epileptic Disord. 2003 Sep;5(3):161-4.
PubMed 14684352
Study at a glance
From the registry record, last updated by the sponsor on 28 May 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Assessment of Subthalamic Nucleus Stimulation in Drug Resistant Epilepsy Associated With Dopaminergic Metabolism Deficit. A Randomized, Double Blind, Controlled Trial.
- ClinicalTrials.gov ID
- NCT00228371
- Acronym / sponsor ID
- DCIC 03 23
- Conditions
- Epilepsy, Drug Resistant
- Keywords
- Epilepsy, deep brain stimulation, Subthalamic nucleus, Drug resistant epilepsy
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: insufficent enrolement
- Enrolment
- 4 participants (actual)
- Lead sponsor
- University Hospital, GrenobleUniversity, hospital or other
- Collaborators
- Ministry of Health, France
- Study start
- Sep 2005
- Primary completion
- Dec 2009 (actual)
- Study completion
- Mar 2010 (actual)
- First posted
- 28 Sep 2005 (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.
The aim of this study is to evaluate the effectiveness and the safety of deep brain stimulation in drug resistant epilepsy.
This is a double blind, controlled and randomized clinical trial with two cross-over groups and four phases.
Phase 1 : base line, open phase consisting of follow-up of patients with their standard treatment.
Phase 2 : Randomisation, lead implantation, followed by 3 months wash out period with the stimulator switch OFF.
Phase 3 : cross-over, double blind phase : 3 months with stimulator switch ON or OFF depending on randomization allocation, followed by 3 months with the stimulator switch on the opposite position. The placebo consisting of turn OFF the stimulator.
Phase 4 : open phase, one year follow-up of all patients with the stimulator switch ON.
Detailed description
The experimental work performed for more than 15 years by several research teams shows in animal models of epilepsy, that several circuits of basal ganglia are involved in the control of epilepsy seizures. The existence of those circuits leads to the possibility of therapeutic applications in particular deep brain stimulation.
Preliminary results (Benabid et al, 2002) (Chabardes et al , 2002) suggest that the neuromodulation of basal ganglia and in particular the subthalamic nucleus and the substantia nigra pars reticulata could have a therapeutic effects in patients with drug resistant epilepsy and no possibility of resection surgery.
This is a double blind, controlled and randomized clinical trial with two cross-over groups and four phases.
Phase 1 : base line, open phase consisting of follow-up of patients with their standard treatment.
Phase 2 : Randomisation, lead implantation, followed by 3 months wash out period with the stimulator switch OFF.
Phase 3 : cross-over, double blind phase : 3 months with stimulator switch ON or OFF depending on randomization allocation, followed by 3 months with the stimulator switch on the opposite position.
Phase 4 : open phase, one year follow-up of all patients with the stimulator switch ON.
There are two differents groups at phase 3 :
- Group A : 10 patients with the stimulator switch ON for three months and switch OFF for the next three months.
- Group B : 10 patients with the opposite sequence, OFF and ON.
Main objective :
- To show that high frequency deep brain stimulation of the subthalamic nucleus decrease the frequency of epileptic seizure compared with no stimulation.
Secondary objectives :
- To show that high frequency deep brain stimulation of the subthalamic nucleus improve the quality of life.
- To describe the side effects of this device and compare with those described in Parkinson patients. In particular to check the onset of dyskinesia related to dopamine.
- To compare the distribution of seizure frequency after stimulation to the base line.
- To show that the number of patients responding to treatment are higher in the group with stimulator switch ON than in the group with the stimulator turn OFF.
- To compare the number of days without seizure with the stimulator switch ON or OFF.
- To evaluated the neuropsychologic effect induced by the neurostimulation
- To quantify the types and the ratio of different seizures during the ON phase and the OFF phase.
- To monitor the secondary drug use during the study.
Control visits : all patients will have a control visit every 4 weeks during the study.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 1 | Other | Device: NeurostimulationThe stimulator is switch ON during the first phase of the cross-over and switch OFF during the second phase |
| 2 | Other | Device: NeurostimulationThe stimulator is switch OFF during the first phase of the cross-over and switch ON during the second phase |
Who may qualify
- Ages
- 18 to 50 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (6 listed)
- Epilepsy resistant to antiepileptic drug and dopaminergic D2 agonist.
- No curative exeresis surgery possible
- Metabolism deficiency of DOPA above 1 DS, evaluated by Positron Emission Tomography (PET) using fluorodopa
- Age ranging from 18 to 50
- capacity to consent
Key exclusion criteria (3 listed)
- pregnant woman or nursing mother
- change of antiepileptic, 30 days before base line
- convulsive "etat de mal" that requires an hospitalisation, 30 days before base line
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 |
|---|---|---|
| NeurostimulationAlso: Neurostimulation of subthalamic nucleusHigh frequency neurostimulation of subthalamic nucleus : quadrupolar electrode, type 3389, n° : I7 02 08 39709 158, Medtronic, Minneapolis, USA | Device | 1, 2 |
Primary outcome
- Daily seizure frequency at each phase
Time frame: at each phase
3 secondary outcomes
The number of days without seizure during each phase
Time frame: at each phase
Quality of life : SEALS, QOLIE-31 and NHP scales
Time frame: at each phase
Neuropsychological test : WAIS, GROBER and Busckhe, Wisconsin Card Sorting Test, TRAIL test, LURIA test, Beck Depression Inventory, verbal flow test, empathy test
Time frame: at each phase
Results and safety
The study was stopped early (reason given: insufficent enrolement). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 May 2015.
- Background: PubMed 1695401Alexander GE, Crutcher MD. Functional architecture of basal ganglia circuits: neural substrates of parallel processing. Trends Neurosci. 1990 Jul;13(7):266-71. doi: 10.1016/0166-2236(90)90107-l.
- Background: PubMed 10443887Ardouin C, Pillon B, Peiffer E, Bejjani P, Limousin P, Damier P, Arnulf I, Benabid AL, Agid Y, Pollak P. Bilateral subthalamic or pallidal stimulation for Parkinson's disease affects neither memory nor executive functions: a consecutive series of 62 patients. Ann Neurol. 1999 Aug;46(2):217-23. doi: 10.1002/1531-8249(199908)46:23.0.co;2-z.
- Background: PubMed 11697687Benabid AL, Koudsie A, Benazzouz A, Vercueil L, Fraix V, Chabardes S, Lebas JF, Pollak P. Deep brain stimulation of the corpus luysi (subthalamic nucleus) and other targets in Parkinson's disease. Extension to new indications such as dystonia and epilepsy. J Neurol. 2001 Sep;248 Suppl 3:III37-47. doi: 10.1007/pl00007825.
- Background: PubMed 12015863Benabid AL, Minotti L, Koudsie A, de Saint Martin A, Hirsch E. Antiepileptic effect of high-frequency stimulation of the subthalamic nucleus (corpus luysi) in a case of medically intractable epilepsy caused by focal dysplasia: a 30-month follow-up: technical case report. Neurosurgery. 2002 Jun;50(6):1385-91; discussion 1391-2. doi: 10.1097/00006123-200206000-00037.
- Background: PubMed 12495878Chabardes S, Kahane P, Minotti L, Koudsie A, Hirsch E, Benabid AL. Deep brain stimulation in epilepsy with particular reference to the subthalamic nucleus. Epileptic Disord. 2002 Dec;4 Suppl 3:S83-93.
- Background: PubMed 9711758Chkhenkeli SA, Chkhenkeli IS. Effects of therapeutic stimulation of nucleus caudatus on epileptic electrical activity of brain in patients with intractable epilepsy. Stereotact Funct Neurosurg. 1997;69(1-4 Pt 2):221-4. doi: 10.1159/000099878.
- Background: PubMed 4206369Cooper IS, Amin I, Gilman S. The effect of chronic cerebellar stimulation upon epilepsy in man. Trans Am Neurol Assoc. 1973;98:192-6. No abstract available.
- Background: PubMed 1695404DeLong MR. Primate models of movement disorders of basal ganglia origin. Trends Neurosci. 1990 Jul;13(7):281-5. doi: 10.1016/0166-2236(90)90110-v.
- Background: PubMed 14684352Dematteis M, Kahane P, Vercueil L, Depaulis A. MRI evidence for the involvement of basal ganglia in epileptic seizures: an hypothesis. Epileptic Disord. 2003 Sep;5(3):161-4.
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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.
Stephan CHABARDES, Dr principal investigator
University Hospital of Grenoble, Neuro surgery
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing Neurostimulation in people with Epilepsy and Drug Resistant, run by University Hospital, Grenoble at 3 sites 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 6 inclusion and 3 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: stopped early, as of the sponsor's last update on 28 May 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites 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.
What does this combined phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: insufficent enrolement). Results are not available in the source record.
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?
- Daily seizure frequency at each phase (time frame: at each phase). 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 NCT00228371, which also lists 9 linked publications.
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 2015.