Refractory EpilepsyNCT03636958
Efficacy and Safety of Perampanel in Combination in Glioma-refractory Epilepsy
A study testing Perampanel and conventional antiepileptic treatment in people with Refractory Epilepsy, run by Assistance Publique Hopitaux De Marseille at 2 sites in France.
Trial summary
Gliomas are primitive brain tumors frequently associated with epilepsy. In a significant number of these patients epilepsy is resistant to antiepileptic drugs. There are currently no recommendations for the management of these drug-resistant epilepsies associated with glioma. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Refractory Epilepsy
- What is being tested?
- Perampanel and conventional antiepileptic treatment
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- 2 sitesFrance
- Study dates
- 15 Feb 2021to 1 Dec 2026
- 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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patient, male or female, over 18 years old
- Glioma confirmed by histology
- Not in progression (clinico-radiological criterion RANO, (Wen et al., 2014), see appendix 1)
- No clinical worsening (excluding epileptic seizures)
- No increase greater than 25% in contrast enhancement after gadolinium injection
- No increase in the T2 / FLAIR hyper signal
Show all 11Show fewer
- Absence of new lesion
- Diagnosis of drug-resistant epilepsy according to international epilepsy definitions (Fisher 2014 and Kwan 2010, see Appendices 2 and 3)
- o Repeated epileptic seizures despite testing of two effective dose antiepileptic drugs tried at least 3 months
- With at least 2 attacks per month (to ensure visibility on the duration of the study of the antiepileptic effect, see below)
- Patient with epileptic seizures not limited to only subjective signs
Who cannot join
- Pregnant or lactating woman
- Minor
- Impossibility of signing consent
- No affiliation to a social security scheme (beneficiary or beneficiary)
- Person in emergency,
- Person of legal age subject to a legal protection measure (major under guardianship, guardianship or court order), or unable to express his or her consent
- Patient with at least 2 generalized tonic-clonic seizures per month.
Trial locations and contacts
2 sites in 1 country.
France2 sites
Assistance Publique Des Hopitaux de Marseille
Marseille, PACA, 13354
Department of Epileptology and Cerebral Rhythmology, Hôpital La Timone, APHM
Marseille, 13385
About this study
Official title: Study of the Efficacy and Safety of Perampanel in Combination in Glioma-refractory Epilepsy
Gliomas are primitive brain tumors frequently associated with epilepsy. In a significant number of these patients epilepsy is resistant to antiepileptic drugs. There are currently no recommendations for the management of these drug-resistant epilepsies associated with glioma. In addition, few studies have addressed the subject and no treatment appears to be superior to others in the literature for this indication. In addition, many antiepileptic drugs pose problems of tolerance or interaction with chemotherapy in these patients.
Fundamental studies on glioma-associated epilepsies have shown that there is a major dysregulation of glutamatergic systems involved in epileptogenesis and tumor growth. Targeting this glutamatergic system seems particularly interesting from a physiopathological point of view. Perampanel is a recent antiepileptic treatment with a novel mode of action targeting AMPA glutamate receptors. It has been shown to be effective in patients with drug-resistant epilepsies. He has demonstrated his tolerance in these patients. He has obtained a marketing authorization and is therefore used in routine epileptology without serious problems of tolerance being reported. It is neither an inducer nor an enzyme inhibitor, avoiding the problems of interaction with chemotherapy and is used in a daily dose facilitating compliance.
Read more
Therefore, there may be specific antiepileptic efficacy of perampanel in patients with glioma. Nevertheless, the only current data is limited to a retrospective study of 12 patients.
The objective of this protocol is to evaluate the efficacy and safety of perampanel in patients with glioma with drug-resistant epilepsy.
a prospective randomized study with two parallel arms: antiepileptic combination therapy with perampanel and antiepileptic combination therapy without perampanel (free choice of the practitioner). The main criterion of judgment will be the decrease of the monthly frequency of crisis. Secondary endpoints will assess tolerance, efficacy on responder rate (at least 50% decrease in seizure frequency), seizure severity (secondary generalization, loss of consciousness), and quality. patients' lives (quality of life questionnaires, side effects and anxiety / depression). The duration of participation per patient will be 23 weeks (6 weeks of baseline, 5 weeks of titration and 12 weeks of maintenance). The recruitment period will be 3 years. Investigators plan to recruit 120 patients.
In the context of no recommendation in the management of these patients, superior efficacy of perampanel compared with other antiepileptic drugs is expected. This would allow targeted treatment in this population and confirm the tolerance of this treatment in these patients.
Read the detailed description
Background: Gliomas are primitive brain tumors frequently associated with epilepsy. In a significant number of these patients epilepsy is resistant to antiepileptic drugs. There are currently no recommendations for the management of these drug-resistant epilepsies associated with glioma. In addition, few studies have addressed the subject and no treatment appears to be superior to others in the literature for this indication. In addition, many antiepileptic drugs pose problems of tolerance or interaction with chemotherapy in these patients.
Rational: Fundamental studies on glioma-associated epilepsies have shown that there is a major dysregulation of glutamatergic systems involved in epileptogenesis (= perpetuation of epileptic seizures) and tumor growth (Huberfeld and Vecht, 2016). Targeting this glutamatergic system seems particularly interesting from a physiopathological point of view. Perampanel is a recent antiepileptic treatment with a novel mode of action targeting AMPA glutamate receptors. It has been shown to be effective in patients with drug-resistant epilepsies. He has demonstrated his tolerance in these patients. He has obtained a marketing authorization and is therefore used in routine epileptology without serious problems of tolerance being reported. It is neither an inducer nor an enzyme inhibitor, avoiding the problems of interaction with chemotherapy and is used in a daily dose facilitating compliance.
Therefore, there may be specific antiepileptic efficacy of perampanel in patients with glioma. Nevertheless, the only current data is limited to a retrospective study of 12 patients.
The objective of this protocol is to evaluate the efficacy and safety of perampanel in patients with glioma with drug-resistant epilepsy.
The investigators want to perform a prospective randomized study with two parallel arms: antiepileptic combination therapy with perampanel and antiepileptic combination therapy without perampanel (free choice of the practitioner). The main criterion of judgment will be the decrease of the monthly frequency of crisis. Secondary endpoints will assess tolerance, efficacy on responder rate (at least 50% decrease in seizure frequency), seizure severity (secondary generalization, loss of consciousness), and quality. patients' lives (quality of life questionnaires, side effects and anxiety / depression). The duration of participation per patient will be 23 weeks (6 weeks of baseline, 5 weeks of titration and 12 weeks of maintenance). The recruitment period will be 3 years. The investigators plan to recruit 120 patients.
Expected benefits: In the context of no recommendation in the management of these patients, the investigators hope to demonstrate superior efficacy of perampanel compared with other antiepileptic drugs. This would allow targeted treatment in this population and confirm the tolerance of this treatment in these patients.
- Conditions
- Refractory Epilepsy
- Being tested
- Perampanel, conventional antiepileptic treatment
- Medical subject headings
- Drug Resistant Epilepsy
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PerampanelDrug
Perampanel is an antiepileptic with a novel mechanism of action as it targets post-synaptic AMPA receptors. It has been shown to be effective as adjunctive therapy (dual therapy) for partial / focal epilepsy seizures and generalized in patients over 12 years of age.
conventional antiepileptic treatmentDrug
choice of the molecule is left to the discretion of the clinician excluding the following benzodiazepines: clobazam, clonazepam, diazepam. Antiepileptic drugs allowed are therefore: lamotrigine, levetiracetam, lacosamide, sodium valproate, carbamazepine, oxcarbabazepine, slicarbazepine, pregabalin, gabapentin, topiramate, phenytoin, phenobarbital, zonisamide, vigabatrin.
| Study group | Role | What they receive |
|---|---|---|
| control group | Active comparator | they will receive conventional antiepileptic treatment (antiepileptic combination therapy) without perampanel Receives: Drug: conventional antiepileptic treatment |
| experimental group | Experimental | they will receive conventional antiepileptic treatment (antiepileptic combination therapy) with perampanel Receives: Drug: Perampanel; Drug: conventional antiepileptic treatment |
What is being measured
The primary outcome is the main question the study is designed to answer.
Numbers of crisis at baseline
The monthly frequency of crisis
Measured: 6 weeks
Numbers of crisis under treatment
The monthly frequency of crisis during treatment period
Measured: 5 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Aug 2018
- Study start15 Feb 2021
- Primary completion1 Jul 2025 (estimated)
- Study completion1 Dec 2026 (estimated)
Why it stopped: concomitant decision of the sponsor and the PI, lack of patients
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Refractory EpilepsyStudies of the same condition, open and under way.
- More trials run by Assistance Publique Hopitaux De MarseilleThe 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
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Assistance Publique Hopitaux De Marseille
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- EMILIE GARRIDO PRADALIE, Study director, APHM
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03636958
- Sponsor's protocol ID
- 2018-13
- Status last verified
- Jun 2022
- First submitted
- 16 Aug 2018
- Last updated
- 27 Jun 2022
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 27 Jun 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Study of the Efficacy and Safety of Perampanel in Combination in Glioma-refractory Epilepsy
- ClinicalTrials.gov ID
- NCT03636958
- Acronym / sponsor ID
- 2018-13
- Conditions
- Refractory Epilepsy
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: concomitant decision of the sponsor and the PI, lack of patients
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Assistance Publique Hopitaux De MarseilleUniversity, hospital or other
- Study start
- 15 Feb 2021 (actual)
- Primary completion
- 1 Jul 2025 (estimated)
- Study completion
- 1 Dec 2026 (estimated)
- First posted
- 17 Aug 2018 (actual)
- 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.
Gliomas are primitive brain tumors frequently associated with epilepsy. In a significant number of these patients epilepsy is resistant to antiepileptic drugs. There are currently no recommendations for the management of these drug-resistant epilepsies associated with glioma. In addition, few studies have addressed the subject and no treatment appears to be superior to others in the literature for this indication. In addition, many antiepileptic drugs pose problems of tolerance or interaction with chemotherapy in these patients.
Fundamental studies on glioma-associated epilepsies have shown that there is a major dysregulation of glutamatergic systems involved in epileptogenesis and tumor growth. Targeting this glutamatergic system seems particularly interesting from a physiopathological point of view. Perampanel is a recent antiepileptic treatment with a novel mode of action targeting AMPA glutamate receptors. It has been shown to be effective in patients with drug-resistant epilepsies. He has demonstrated his tolerance in these patients. He has obtained a marketing authorization and is therefore used in routine epileptology without serious problems of tolerance being reported. It is neither an inducer nor an enzyme inhibitor, avoiding the problems of interaction with chemotherapy and is used in a daily dose facilitating compliance.
Therefore, there may be specific antiepileptic efficacy of perampanel in patients with glioma. Nevertheless, the only current data is limited to a retrospective study of 12 patients.
The objective of this protocol is to evaluate the efficacy and safety of perampanel in patients with glioma with drug-resistant epilepsy.
a prospective randomized study with two parallel arms: antiepileptic combination therapy with perampanel and antiepileptic combination therapy without perampanel (free choice of the practitioner). The main criterion of judgment will be the decrease of the monthly frequency of crisis. Secondary endpoints will assess tolerance, efficacy on responder rate (at least 50% decrease in seizure frequency), seizure severity (secondary generalization, loss of consciousness), and quality. patients' lives (quality of life questionnaires, side effects and anxiety / depression). The duration of participation per patient will be 23 weeks (6 weeks of baseline, 5 weeks of titration and 12 weeks of maintenance). The recruitment period will be 3 years. Investigators plan to recruit 120 patients.
In the context of no recommendation in the management of these patients, superior efficacy of perampanel compared with other antiepileptic drugs is expected. This would allow targeted treatment in this population and confirm the tolerance of this treatment in these patients.
Detailed description
Background: Gliomas are primitive brain tumors frequently associated with epilepsy. In a significant number of these patients epilepsy is resistant to antiepileptic drugs. There are currently no recommendations for the management of these drug-resistant epilepsies associated with glioma. In addition, few studies have addressed the subject and no treatment appears to be superior to others in the literature for this indication. In addition, many antiepileptic drugs pose problems of tolerance or interaction with chemotherapy in these patients.
Rational: Fundamental studies on glioma-associated epilepsies have shown that there is a major dysregulation of glutamatergic systems involved in epileptogenesis (= perpetuation of epileptic seizures) and tumor growth (Huberfeld and Vecht, 2016). Targeting this glutamatergic system seems particularly interesting from a physiopathological point of view. Perampanel is a recent antiepileptic treatment with a novel mode of action targeting AMPA glutamate receptors. It has been shown to be effective in patients with drug-resistant epilepsies. He has demonstrated his tolerance in these patients. He has obtained a marketing authorization and is therefore used in routine epileptology without serious problems of tolerance being reported. It is neither an inducer nor an enzyme inhibitor, avoiding the problems of interaction with chemotherapy and is used in a daily dose facilitating compliance.
Therefore, there may be specific antiepileptic efficacy of perampanel in patients with glioma. Nevertheless, the only current data is limited to a retrospective study of 12 patients.
The objective of this protocol is to evaluate the efficacy and safety of perampanel in patients with glioma with drug-resistant epilepsy.
The investigators want to perform a prospective randomized study with two parallel arms: antiepileptic combination therapy with perampanel and antiepileptic combination therapy without perampanel (free choice of the practitioner). The main criterion of judgment will be the decrease of the monthly frequency of crisis. Secondary endpoints will assess tolerance, efficacy on responder rate (at least 50% decrease in seizure frequency), seizure severity (secondary generalization, loss of consciousness), and quality. patients' lives (quality of life questionnaires, side effects and anxiety / depression). The duration of participation per patient will be 23 weeks (6 weeks of baseline, 5 weeks of titration and 12 weeks of maintenance). The recruitment period will be 3 years. The investigators plan to recruit 120 patients.
Expected benefits: In the context of no recommendation in the management of these patients, the investigators hope to demonstrate superior efficacy of perampanel compared with other antiepileptic drugs. This would allow targeted treatment in this population and confirm the tolerance of this treatment in these patients.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| control group | Active comparator | Drug: conventional antiepileptic treatmentthey will receive conventional antiepileptic treatment (antiepileptic combination therapy) without perampanel |
| experimental group | Experimental | Drug: Perampanel, Drug: conventional antiepileptic treatmentthey will receive conventional antiepileptic treatment (antiepileptic combination therapy) with perampanel |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- Patient, male or female, over 18 years old
- Glioma confirmed by histology
- Not in progression (clinico-radiological criterion RANO, (Wen et al., 2014), see appendix 1)
- Diagnosis of drug-resistant epilepsy according to international epilepsy definitions (Fisher 2014 and Kwan 2010, see Appendices 2 and 3)
- o Repeated epileptic seizures despite testing of two effective dose antiepileptic drugs tried at least 3 months
Key exclusion criteria (7 listed)
- Pregnant or lactating woman
- Minor
- Impossibility of signing consent
- No affiliation to a social security scheme (beneficiary or beneficiary)
- Person in emergency,
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 |
|---|---|---|
| PerampanelPerampanel is an antiepileptic with a novel mechanism of action as it targets post-synaptic AMPA receptors. It has been shown to be effective as adjunctive therapy (dual therapy) for partial / focal epilepsy seizures and generalized in patients over 12 years of age. | Drug | experimental group |
| conventional antiepileptic treatmentchoice of the molecule is left to the discretion of the clinician excluding the following benzodiazepines: clobazam, clonazepam, diazepam. Antiepileptic drugs allowed are therefore: lamotrigine, levetiracetam, lacosamide, sodium valproate, carbamazepine, oxcarbabazepine, slicarbazepine, pregabalin, gabapentin, topiramate, phenytoin, phenobarbital, zonisamide, vigabatrin. | Drug | control group, experimental group |
Primary outcome
Numbers of crisis at baseline
Time frame: 6 weeks
The monthly frequency of crisis
Numbers of crisis under treatment
Time frame: 5 weeks
The monthly frequency of crisis during treatment period
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Jun 2022.
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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.
EMILIE GARRIDO PRADALIE study director
APHM
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Perampanel and conventional antiepileptic treatment in people with Refractory Epilepsy, run by Assistance Publique Hopitaux De Marseille at 2 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 11 inclusion and 7 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: withdrawn, as of the sponsor's last update on 27 Jun 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 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.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
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?
Numbers of crisis at baseline (time frame: 6 weeks). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 27 Jun 2022.