EpilepsyDRAPETONINENCT07013331
A PET-MRI Study of Serotoninergic Brainstem Pathway in Patients With Dravet Syndrome
A study testing [18F]MPPF PET-MRI in people with Epilepsy and Dravet Syndrome, run by Hospices Civils de Lyon at 1 site in France.
Trial summary
Dravet Syndrome (DS) is a severe neurodevelopmental disease, which is predominantly caused by mutations of SCN1A, the gene coding for Nav1.1 voltage-gated sodium channels. DS is characterized by infancy onset, severe cognitive deficit and drug-resistant seizures, including several generalized convulsive seizures per… Read more about this study
- Who is it for?
- Ages 18 to 60 yearsHealthy volunteers can take part
- Conditions the study is for
- Epilepsy, Dravet Syndrome, Drug Resistant Epilepsy
- What is being tested?
- [18F]MPPF PET-MRI
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 30 participants
- Where
- 1 siteFrance
- Study dates
- 4 May 2026to 4 Jan 2028
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
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 60 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- Adult patients (≥ 18 but < 60 years)
- Diagnosis of Dravet syndrome will be confirmed based on medical history, type of seizures, EEG data and results of genetic testing
- No restriction related to the seizure frequency
- Patient assent and patient (or patient's legal representative guardianship) who gave its written informed consent to participate to the study
- For women of childbearing
- Adult patient (≥ 18 years)
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- Patient suffering from drug-resistant focal epilepsy according to ILAE classification
- Patient in whom presurgical evaluation is considered
- No restriction related to the seizure frequency
- Patient who gave her/his written informed consent to participate to the study
- For women of childbearing potential, use highly effective contraception during study participation
- Presence of the symptoms of anxiety and/or depression as defined by a score ≥ 11 at the French version of the Hospital Anxiety and Depression Scale (HADS)
- Ongoing treatment with selective serotonin reuptake inhibitor
- MRI contra-indication (presence of metallic elements, claustrophobia)
- Pregnant women, women in labor or breastfeeding women.
- Severe renal failure (Glomerular filtration rate < 30 ml/min)
- Hypersensitivity to [18F] MPPF
- Persons deprived of their liberty by a judicial or administrative decision
- Persons under psychiatric care
- Persons admitted to a health or social institution for purposes other than research
- Adults subject to a legal protection measure (guardianship, curatorship)
- Persons not affiliated to a social security scheme or beneficiaries of a similar scheme
Who cannot join
- Subject in exclusion period of another study
- MRI contra-indication (presence of metallic elements, claustrophobia, Patients unable to maintain a minimul level of immobility during the imaging acquisition)
- Presence of Vagal Nerve Stimulation
- Patients unable to maintain a minimul level of immobility during the imaging acquisition
- Pregnant women, women in labor or breastfeeding women.
- Severe renal failure (Glomerular filtration rate < 30 ml/min)
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- Hypersensitivity to [18F] MPPF
- Persons deprived of their liberty by a judicial or administrative decision
- Persons under psychiatric care
- Persons not affiliated to a social security scheme or beneficiaries of a similar scheme
- Patients with drug-resistant focal epilepsy
- Subject in exclusion period of another study
- MRI contra-indication (presence of metallic elements, claustrophobia)
- Presence of Vagal Nerve Stimulation
- Ongoing serotoninergic treatment, including selective serotonin reuptake inhibitor
- Pregnant women, women in labor or breastfeeding women.
- Severe renal failure (Glomerular filtration rate < 30 ml/min)
- Hypersensitivity to [18F] MPPF
- Persons deprived of their liberty by a judicial or administrative decision
- Persons under psychiatric care
- Persons admitted to a health or social institution for purposes other than research
- Adults subject to a legal protection measure (guardianship, curatorship)
- Persons not affiliated to a social security scheme or beneficiaries of a similar scheme
- Healthy controls
- Presence of the symptoms of anxiety and/or depression as defined by a score ≥ 11 at the French version of the Hospital Anxiety and Depression Scale (HADS)
- Ongoing treatment with selective serotonin reuptake inhibitor
- MRI contra-indication (presence of metallic elements, claustrophobia)
- Pregnant women, women in labor or breastfeeding women.
- Severe renal failure (Glomerular filtration rate < 30 ml/min)
- Hypersensitivity to [18F] MPPF
- Persons deprived of their liberty by a judicial or administrative decision
- Persons under psychiatric care
- Persons admitted to a health or social institution for purposes other than research
- Adults subject to a legal protection measure (guardianship, curatorship)
- Persons not affiliated to a social security scheme or beneficiaries of a similar scheme
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
France1 site, 1 recruiting
- Recruiting
Hôpital Neurologique Pierre Wertheimer
Bron, Rhone, 69500
Sylvain Rheims, Pr, 0472357106 ext. +33, Sylvain.rheims@chu-lyon.fr
Camille Giraudon, 04 26 73 94 38 ext. +33, Camille.giraudon@chu-lyon.fr
About this study
Dravet Syndrome (DS) is a severe neurodevelopmental disease, which is predominantly caused by mutations of SCN1A, the gene coding for Nav1.1 voltage-gated sodium channels. DS is characterized by infancy onset, severe cognitive deficit and drug-resistant seizures, including several generalized convulsive seizures per day and frequent status epilepticus, often triggered by fever or hyperthermia. Among the causes of premature deaths in patients with epilepsy, sudden and unexpected death in epilepsy (SUDEP) represents a major cause. SUDEP is a non-traumatic and non-drowning death in patients with epilepsy, unrelated to a documented status epilepticus. The risk of SUDEP is particularly high in patients suffering from DS, reaching about 9/1000-person-year, as compared to about 1/1000-person-year in people with epilepsy including all disease types. The main clinical risk factor of SUDEP is the frequency of convulsive seizures. Beyond improving seizure control, which we showed to mitigate the SUDEP risk, more specific preventive treatment strategies are still lacking.
Experimental and clinical data suggest that most SUDEP cases result from postictal brainstem dysfunction, including central respiratory arrest There is a body of evidence suggesting involvement of serotonin (5HT) dysfunction both in the pathogenesis of epilepsy in DS and in seizure-related respiratory dysfunction. Serotonin indeed plays a key role in the regulation of respiration. Population firing of serotoninergic neurons in the medullary raphe is significantly decreased during the ictal and post-ictal periods, in association with decreased breathing and heart rate during and after seizures. Most importantly, post-mortem data in patients, including DS, showed alteration of neuronal populations in the medulla in SUDEP cases with evidence for greater reduction in neuromodulatory neuropeptidergic and monoaminergic, including serotoninergic, systems.
Read more
SUDEP in DS might therefore be the result of a seizure-induced fatal apnea in a patient who has developed epilepsy-related vulnerability to central respiratory dysfunction favored by 5HT dysfunction. However, several issues remain to be addressed to identify detailed mechanisms and effective therapies. Among them, a key issue is the exact relation between the alterations of the 5HT pathway observed in DS and epilepsy-related respiratory dysfunction
In the present study, the hypothesis is that adult patients with DS might demonstrate specific alterations of the 5HT pathway within the brainstem as assessed by PET imaging. The DRAPETOTINE study will thus focus on imaging 5HT brainstem pathway with PET and MRI in patients with DS to assess if abnormalities can be observed and through comparison with data collected in patients drug-resistant focal epilepsy whether these abnormalities are DS specficic or reflect the consequence on brainstem 5HT pathway of refractory seizures.
This study will involve 20 adult patients, including 10 adults with established diagnosis of Dravet Syndrome and 10 patients with drug-resistant focal epilepsy. Ten healthy adults will also be included. Participants will be recruited over a period of 18 months and the duration of participation for each participant will be 2 weeks to 8 weeks
- Conditions
- Epilepsy, Dravet Syndrome, Drug Resistant Epilepsy, Healthy Controls
- Being tested
- [18F]MPPF PET-MRI
- Keywords
- epilepsy, Dravet syndrome, drug-resistant focal epilepsy, serotonin, PET-MRI, MPPF, SUDEP
- Medical subject headings
- Epilepsy, Epilepsies, Myoclonic, Drug Resistant Epilepsy, Sudden Unexpected Death in Epilepsy
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
[18F]MPPF PET-MRIOther
Patients will be seen during an first inclusion visit during which a review of eligibility criteria, medical history and a clinical examination will be done. Participants will be scheduled for a PET-MRI scan within 2 to 8 weeks. For all women of childbearing age a urine pregnancy test will be performed before the PET-MRI.
Anatomical MR imaging will be first acquired for anatomical co-registration and morphometry analyses (Neuromelanin sensitive images and 3D anatomical T1-weighted covering the whole brain volume with 1mm3 cubic voxels) After i.v. injection of a bolus of 180 MBq ± 10%, with a maximum of 198 MBq MBq, of [18F]-MPPF, a dynamic emission scan consisting of 35 frames of increasing duration (20s to 5min) will be acquired over 90-min post-injection
| Study group | Role | What they receive |
|---|---|---|
| Patients with Dravet syndrome | Experimental | Adult patients with Dravet syndrome (> 18 and < 60 years). Diagnosis of Dravet syndrome will be confirmed based on medical history, type of seizures, EEG data and results of genetic testing. Ten DS patients will be recruited and will be passed the PET-IRM with injection of the tracer [18F]MPPF. Receives: Other: [18F]MPPF PET-MRI |
| Patients with drug-resistant focal epilepsy | Experimental | Adult patients (> 18 years) with drug-resistant focal epilepsy, as defined by the ILAE, and whom presurgical evaluation is considered. Ten patients will be recruited and will be passed the PET-IRM with injection of the tracer [18F]MPPF. Receives: Other: [18F]MPPF PET-MRI |
| Adult healthy controls (> 18 years) | Experimental | Ten healthy controls will be recruited and will be passed the PET-IRM with injection of the tracer [18F]MPPF. Participants must be of legal age. Receives: Other: [18F]MPPF PET-MRI |
What is being measured
The primary outcome is the main question the study is designed to answer.
Comparison of the brainstem BPND of [18F]-MPPF across patients groups (DS and focal epilepsy)
Dynamic PET images will be modelled using a simplified reference tissue model to estimate non-displaceable binding potential (BPND) values in each voxel with reference to the cerebellar white matter excluding the vermis.
Measured: Emission will be acquired over 90 minutes post-injection
Secondary outcomes (4)
Relation between the brainstem BPND of [18F]-MPPF and the total duration of central sleep apneas during total sleep time over a 24-hour period in patients with DS
The total duration of central sleep apnea has been preferred to the total number of episodes of central sleep apnea as primary endpoint in order to take into account both the occurrence rate and the severity of episodes. To take into account the variability of the total sleep time across patients, the total duration of central sleep apneas will be expressed as the percentage of the total sleep time for each patient. Sleep apneas can classified as obstructive, central or both central sleep apnea, Apnea will be defined as a decrease in peak nasal pressure of >90% of baseline, lasting at least 10 s. Hypopnea was defined as a decrease of >30% of the baseline nasal pressure, lasting at least 10 s and associated with ≥4% drop in SpO2. Central apnea will be defined by cessation > 10 seconds of airflow with simultaneous cessation of respiratory effort. The respiratory events are scored in clinical routine according to the 2007 American Academy of Sleep Medicine guidelines.
Measured: at Visit 2 (week 2)
Comparing brainstem volume of patients with DS with the one of patients with drug-resistant focal epilepsy
Comparing VBM on the brainstem parcels of patients with DS with the one of patients with drug-resistant focal epilepsy
Measured: at Visit 2 (week 2)
Relation in DS between brainstem volumes and the total duration of central sleep apneas during total sleep time over a 24-hour period
Measured: at Visit 2 (week 2)
Signal-noise radioactivity ratio of 5-HT1A receptors binding in healthy subjects
Comparing the signal-noise radioactivity ratio of 5-HT1A receptors binding in healthy subjects with the one observed with the old PET camera used to develop the CERMEP normative database of 5-HT1A receptors binding in adults
Measured: at Visit 2 (week 2)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Jun 2025
- Study start4 May 2026
- Primary completion4 Jan 2028 (estimated)
- Study completion4 Jan 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for EpilepsyStudies 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
- Screening
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 30 participants (estimated)
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
- NCT07013331
- Sponsor's protocol ID
- 69HCL24_1231
- Acronym
- DRAPETONINE
- Status last verified
- May 2026
- First submitted
- 25 Apr 2025
- Last updated
- 8 May 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 8 May 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A PET-MRI Study of Serotoninergic Brainstem Pathway in Patients With Dravet Syndrome
- ClinicalTrials.gov ID
- NCT07013331
- Acronym / sponsor ID
- DRAPETONINE / 69HCL24_1231
- Conditions
- Epilepsy, Dravet Syndrome, Drug Resistant Epilepsy, Healthy Controls
- Keywords
- epilepsy, Dravet syndrome, drug-resistant focal epilepsy, serotonin, PET-MRI, MPPF, SUDEP
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 30 participants (estimated)
- Lead sponsor
- Hospices Civils de LyonUniversity, hospital or other
- Study start
- 4 May 2026 (actual)
- Primary completion
- 4 Jan 2028 (estimated)
- Study completion
- 4 Jan 2028 (estimated)
- First posted
- 10 Jun 2025 (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.
Dravet Syndrome (DS) is a severe neurodevelopmental disease, which is predominantly caused by mutations of SCN1A, the gene coding for Nav1.1 voltage-gated sodium channels. DS is characterized by infancy onset, severe cognitive deficit and drug-resistant seizures, including several generalized convulsive seizures per day and frequent status epilepticus, often triggered by fever or hyperthermia. Among the causes of premature deaths in patients with epilepsy, sudden and unexpected death in epilepsy (SUDEP) represents a major cause. SUDEP is a non-traumatic and non-drowning death in patients with epilepsy, unrelated to a documented status epilepticus. The risk of SUDEP is particularly high in patients suffering from DS, reaching about 9/1000-person-year, as compared to about 1/1000-person-year in people with epilepsy including all disease types. The main clinical risk factor of SUDEP is the frequency of convulsive seizures. Beyond improving seizure control, which we showed to mitigate the SUDEP risk, more specific preventive treatment strategies are still lacking.
Experimental and clinical data suggest that most SUDEP cases result from postictal brainstem dysfunction, including central respiratory arrest There is a body of evidence suggesting involvement of serotonin (5HT) dysfunction both in the pathogenesis of epilepsy in DS and in seizure-related respiratory dysfunction. Serotonin indeed plays a key role in the regulation of respiration. Population firing of serotoninergic neurons in the medullary raphe is significantly decreased during the ictal and post-ictal periods, in association with decreased breathing and heart rate during and after seizures. Most importantly, post-mortem data in patients, including DS, showed alteration of neuronal populations in the medulla in SUDEP cases with evidence for greater reduction in neuromodulatory neuropeptidergic and monoaminergic, including serotoninergic, systems.
SUDEP in DS might therefore be the result of a seizure-induced fatal apnea in a patient who has developed epilepsy-related vulnerability to central respiratory dysfunction favored by 5HT dysfunction. However, several issues remain to be addressed to identify detailed mechanisms and effective therapies. Among them, a key issue is the exact relation between the alterations of the 5HT pathway observed in DS and epilepsy-related respiratory dysfunction
In the present study, the hypothesis is that adult patients with DS might demonstrate specific alterations of the 5HT pathway within the brainstem as assessed by PET imaging. The DRAPETOTINE study will thus focus on imaging 5HT brainstem pathway with PET and MRI in patients with DS to assess if abnormalities can be observed and through comparison with data collected in patients drug-resistant focal epilepsy whether these abnormalities are DS specficic or reflect the consequence on brainstem 5HT pathway of refractory seizures.
This study will involve 20 adult patients, including 10 adults with established diagnosis of Dravet Syndrome and 10 patients with drug-resistant focal epilepsy. Ten healthy adults will also be included. Participants will be recruited over a period of 18 months and the duration of participation for each participant will be 2 weeks to 8 weeks
Study design
- Primary purpose
- Screening
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Patients with Dravet syndrome | Experimental | Other: [18F]MPPF PET-MRIAdult patients with Dravet syndrome (> 18 and < 60 years). Diagnosis of Dravet syndrome will be confirmed based on medical history, type of seizures, EEG data and results of genetic testing. Ten DS patients will be recruited and will be passed the PET-IRM with injection of the tracer [18F]MPPF. |
| Patients with drug-resistant focal epilepsy | Experimental | Other: [18F]MPPF PET-MRIAdult patients (> 18 years) with drug-resistant focal epilepsy, as defined by the ILAE, and whom presurgical evaluation is considered. Ten patients will be recruited and will be passed the PET-IRM with injection of the tracer [18F]MPPF. |
| Adult healthy controls (> 18 years) | Experimental | Other: [18F]MPPF PET-MRITen healthy controls will be recruited and will be passed the PET-IRM with injection of the tracer [18F]MPPF. Participants must be of legal age. |
Who may qualify
- Ages
- 18 to 60 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (22 listed)
Key exclusion criteria (35 listed)
- Patients with drug-resistant focal epilepsy
- Healthy controls
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 |
|---|---|---|
| [18F]MPPF PET-MRIPatients will be seen during an first inclusion visit during which a review of eligibility criteria, medical history and a clinical examination will be done. Participants will be scheduled for a PET-MRI scan within 2 to 8 weeks. For all women of childbearing age a urine pregnancy test will be performed before the PET-MRI. Anatomical MR imaging will be first acquired for anatomical co-registration and morphometry analyses (Neuromelanin sensitive images and 3D anatomical T1-weighted covering the whole brain volume with 1mm3 cubic voxels) After i.v. injection of a bolus of 180 MBq ± 10%, with a maximum of 198 MBq MBq, of [18F]-MPPF, a dynamic emission scan consisting of 35 frames of increasing duration (20s to 5min) will be acquired over 90-min post-injection | Other | Adult healthy controls (> 18 years), Patients with Dravet syndrome, Patients with drug-resistant focal epilepsy |
Primary outcome
Comparison of the brainstem BPND of [18F]-MPPF across patients groups (DS and focal epilepsy)
Time frame: Emission will be acquired over 90 minutes post-injection
Dynamic PET images will be modelled using a simplified reference tissue model to estimate non-displaceable binding potential (BPND) values in each voxel with reference to the cerebellar white matter excluding the vermis.
4 secondary outcomes
Relation between the brainstem BPND of [18F]-MPPF and the total duration of central sleep apneas during total sleep time over a 24-hour period in patients with DS
Time frame: at Visit 2 (week 2)
Comparing brainstem volume of patients with DS with the one of patients with drug-resistant focal epilepsy
Time frame: at Visit 2 (week 2)
Relation in DS between brainstem volumes and the total duration of central sleep apneas during total sleep time over a 24-hour period
Time frame: at Visit 2 (week 2)
Signal-noise radioactivity ratio of 5-HT1A receptors binding in healthy subjects
Time frame: at Visit 2 (week 2)
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 May 2026.
- Individual participant dataSharing planned: No
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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.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing [18F]MPPF PET-MRI in people with Epilepsy and Dravet Syndrome, 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 22 inclusion and 35 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: looking for participants now, as of the sponsor's last update on 8 May 2026. 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?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Sylvain Rheims, Pr (0472357106 ext. +33, Sylvain.rheims@chu-lyon.fr), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Comparison of the brainstem BPND of [18F]-MPPF across patients groups (DS and focal epilepsy) (time frame: Emission will be acquired over 90 minutes post-injection). 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 8 May 2026.