EpilepsyBRAVENCT07249034
Impact of Epilepsy on the Brainstem Adenosine Pathway and Its Relation With Arousal and Respiratory Reactivity
A study testing 1 Hypercapnic challenge while participant is awake and PET/MRI acquisition in people with Epilepsy and Drug-resistant Focal Epilepsy, run by Hospices Civils de Lyon at 1 site in France.
Trial summary
Despite the continuous development of new antiseizure medications over the past 25 years, 30% of patients with epilepsy suffer from drug-resistant seizures and are at risk of epilepsy-related complications, like cognitive dysfunctions, sleep-disordered breathing or Sudden and Unexpected Death in Epilepsy (SUDEP). Read more about this study
- Who is it for?
- Ages 18 to 55 yearsHealthy volunteers can take part
- Conditions the study is for
- Epilepsy, Drug-resistant Focal Epilepsy, Healthy Controls
- What is being tested?
- 1 Hypercapnic challenge while participant is awake and PET/MRI acquisition
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 50 participants
- Where
- 1 siteFrance
- Study dates
- 1 Oct 2026to 1 Dec 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 55 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- For patients
- Written informed consent obtained from study subject and ability for study subject to comply with the requirements of the study
- Aged 18 to 55 years old
- Diagnosis of focal epilepsy or of idiopathic generalized epilepsy, as defined by the International League Against Epilepsy
- Diagnosis of refractory epilepsy, as defined by the International League Against Epilepsy as failure of adequate trials of two tolerated, appropriately chosen and used antiseizure drug schedules (whether as monotherapies or in combination) to achieve sustained seizure freedom
- Patients with ≥3 focal to bilateral tonic-clonic seizure (FBTCS) or generalized tonic-clonic seizure (GTCS) during the past 18 months
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- For women of childbearing potential, use highly effective contraception until the end of relevant systemic exposure (V2)
- For healthy volunteers
- Written informed consent obtained from study subject and ability for study subject to comply with the requirements of the study
- Aged 18 to 55 years old
- For women of childbearing potential, use highly effective contraception until the end of relevant systemic exposure (V2)
Who cannot join
- For patients
- Ongoing or chronic respiratory insufficiency defined as breathlessness Grade ≥ 2 using the modified Medical Research Council Dyspnea Scale and/or patient treated by a pneumologist for respiratory insufficiency
- Cardiac insufficiency defined as symptoms Grade ≥ 2 using New York Heart Association Functional Classification and/or patient treated by a cardiologist for chronic heart failure
- Ischaemic heart disease defined as history of myocardial ischemia and/or of typical angina confirmed by a cardiologist.
- Obstructive sleep-apnea syndrome, defined as participant who had been diagnosed for Obstructive sleep apnoea by polysomnography, whether a dedicated therapy is ongoing or not
- Ongoing treatment with selective serotonin reuptake inhibitor (Selective Serotonin Reuptake Inhibitors): Citalopram, Escitalopram, Fluoxetine, Fluvoxamine, Paroxetine, Sertraline and SNRIs (Serotonin-Norepinephrine Reuptake Inhibitors): Duloxetine, Milnacipran, Venlafaxine
Show all 32Show fewer
- Hypercapnic challenges contra-indication (History of stroke in the last 5 years, space-occupying lesion in the brain associated with brain oedema and/or mass effect on MRI/CT scan)
- MRI contra-indication (presence of metallic elements, claustrophobia)
- Patient treated with vagal nerve stimulation or deep brain stimulation
- Pregnant women, women in labor or breastfeeding women, based on declarations at V0
- Patients suffering from a psychiatric disorder, regardless of its etiology, whose care is provided under compulsory measures
- Persons deprived of their liberty by a judicial or administrative decision
- Adults subject to a legal protection measure (guardianship, curatorship)
- Persons not affiliated to a social security scheme or beneficiaries of a similar scheme
- Positive urine pregnancy test at V2, if applicable
- Hypersensitivity to [18F]-CPFPX
- For healthy volunteers
- History of epilepsy
- Ongoing or chronic respiratory insufficiency defined as breathlessness Grade ≥ 2 using the modified Medical Research Council Dyspnea Scale and/or patient treated by a pneumologist for respiratory insufficiency
- Cardiac insufficiency defined as symptoms Grade ≥ 2 using New York Heart Association Functional Classification and/or patient treated by a cardiologist for chronic heart failure
- Ischaemic heart disease defined as history of myocardial ischemia and/or of typical angina confirmed by a cardiologist.
- Obstructive sleep-apnea syndrome, defined as participant who had been diagnosed for Obstructive sleep apnoea by polysomnography, whether a dedicated therapy is ongoing or not
- Ongoing treatment with selective serotonin reuptake inhibitor : SSRIs (Selective Serotonin Reuptake Inhibitors) : Citalopram, Escitalopram, Fluoxetine, Fluvoxamine, Paroxetine, Sertraline and SNRIs (Serotonin-Norepinephrine Reuptake Inhibitors) : Duloxetine, Milnacipran, Venlafaxine
- Hypercapnic challenges contra-indication (History of stroke in the last 5 years, space-occupying lesion in the brain associated with brain oedema and/or mass effect on MRI/CT scan)
- MRI contra-indication (presence of metallic elements, claustrophobia)
- Pregnant women, women in labor or breastfeeding women, based on declarations at V0
- Patients suffering from a psychiatric disorder, regardless of its etiology, whose care is provided under compulsory measures
- Persons deprived of their liberty by a judicial or administrative decision
- Adults subject to a legal protection measure (guardianship, curatorship)
- Persons not affiliated to a social security scheme or beneficiaries of a similar scheme
- Positive urine pregnancy test at V2, if applicable
- Hypersensitivity to [18F]-CPFPX
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
Hospices Civils de Lyon
Bron, 69500
Sylvain RHEIMS, PH PH, +33472357106, sylvain.rheims@chu-lyon.fr
Mathilde LECLERCQ, CP, +33472355838, Mathilde.leclercq@chu-lyon.fr
About this study
Despite the continuous development of new antiseizure medications over the past 25 years, 30% of patients with epilepsy suffer from drug-resistant seizures and are at risk of epilepsy-related complications, like cognitive dysfunctions, sleep-disordered breathing or Sudden and Unexpected Death in Epilepsy (SUDEP). SUDEP typically occurs during sleep, after a nocturnal seizure, and primarily results from a postictal central respiratory dysfunction in patients with generalized convulsive seizure (GCS), suggesting that interaction between respiratory dysfunction and sleep state may play a role in its pathophysiology.
Post-mortem data in SUDEP patients showed alteration of neuronal populations involved in respiratory control in the medulla. Accordingly, pharmacologic strategies aimed at reducing the severity of postictal respiratory dysfunction has appeared as one of the most promising way to prevent SUDEP. However, no encouraging result has hitherto been reported.
Read more
Interconnections between the complex network that regulates arousal and sleep and the respiratory network are numerous. They primarily include the relation between chemosensitive regulation and arousal system to ensure asphyxia-induced arousal (i.e. arousal to elevated CO2), especially through serotonin (5HT)-dependent connections in brain stem. The link between alterations of the brainstem networks involved in arousal regulation and respiratory dysfunction has not been characterized in patients with epilepsy yet.
Like 5HT, adenosine is deeply implicated in the regulation of sleep and central respiratory control.
Seizures transiently increase adenosine extracellular levels. Adenosine physiological effects in the brain are mediated through the activation of two types of Adenosine receptors (ARs), A1Rs and A2ARs. Extracellular adenosine promotes sleep via A1R-dependant inhibition of glutamatergic neurons in the basal forebrain, but also via A2AR-dependant activation of neurons in the nucleus accumbens. Respiration is also inhibited by A1R and A2AR. Most importantly, it has been shown that drug-resistant epilepsy is associated with long-term alterations of ARs cortical expression. However, whether or not a similar epilepsy-related plasticity of ARs occurs in the brainstem and may participate to chronic arousal and respiratory dysfunction in epilepsy has never been investigated.
Considering the tight interplay between central respiratory control, arousal regulation and brainstem adenosine, the main hypothesis of the BRAVE study is that epilepsy might result in alterations of the distribution of A1Rs in the brainstem structures involved in respiratory regulation and/or arousal control, especially in the brainstem structures involved in respiratory regulation under hypercapnic condition.
The study combines clinical respiratory characterization, morphological, functional and metabolic imaging, using the hybrid simultaneous 3T MRI-PET scanner (Siemens Biograph mMR) of the CERMEP. Combining PET with anatomical and functional MR imaging enables non-invasively in vivo mapping of receptor binding and functional neuronal assessment of a physiological task in the entire brain with high spatial resolution.
Investigators already performed fMRI study of respiratory centers, showing number of functional changes in brainstem regions participating to the central control of respiration, including reduced activation during breath-holding fMRI, in patients with epilepsy. The BRAVE study will use the same respiratory paradigm as the one used in this past study.
PET imaging will be focused on A1R, using [18F]CPFPX, a selective A1R antagonist.
- Conditions
- Epilepsy, Drug-resistant Focal Epilepsy, Healthy Controls
- Being tested
- 1 Hypercapnic challenge while participant is awake, PET/MRI acquisition
- Keywords
- Epilepsy, adenosine pathway, respiratory reactivity, PET-MRI, [18F]CPFPX
- Medical subject headings
- Epilepsy
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
1 Hypercapnic challenge while participant is awakeProcedure or surgery
The healthy patient/subject breathes through the mouth, using a mouthpiece and a nose clip, through a device fitted with a hermetically sealed bag that measures the various parameters of his/her breathing. At the start of the test, the healthy patient/subject breathes ambient air and his or her breathing is measured. Then, after a few minutes, the healthy patient/subject is connected to the bag, breathing in a closed circuit. This causes a gradual increase in carbon dioxide (CO2) in the inspired air. During this time, breathing parameters will be measured and gas exchanges studied with each breath. The test is stopped when the end-tidal carbon dioxide pressure (PetCO2) reaches 60 mm Hg, or in the event of intolerance
PET/MRI acquisitionProcedure or surgery
The PET/MRI acquisition will be organized into 3 parts for a total duration of 120 minutes from the injection of the radiotracer
- Baseline (0-70 min)
- Respiratory challenge (70-100 min) : Subjects will perform three series of expiratory breath holds (six repeats during each run). A green dot will be shown for 30 seconds, indicating that the patient can still breathe normally for 30 seconds. Then, a yellow dot appears for two seconds, indicating that the patient needs to prepare himself for an expiratory BH that shall start at the end of an expiration, and at the end of the two seconds. Then a red dot appears indicating that the patient must hold his breath while being in full expiration or inspiration. The red dot remains until the patient decides to breath again and push a button to alert us of re-breathing. Screen turns black for 60 seconds before another sequence starts (30 sec. green dot).
- Return to equilibrium (100-120 min).
| Study group | Role | What they receive |
|---|---|---|
| Patients with drug-resistant epilepsy | Experimental | Diagnosis of refractory focal epilepsy or of refractory idiopathic generalized epilepsy, as defined by the International League Against Epilepsy.
The following procedures will be carried out as part of the research:
* Hypercapnic challenge
* PET/MRI acquisition with [18F]-CPFPX Baseline (0-70 min) Hypercapnic challenge (Breath holding) (70-100 min) Return to equilibrium (100-120 min) Receives: Procedure: 1 Hypercapnic challenge while participant is awake; Procedure: PET/MRI acquisition |
| Healthy subjects | Experimental | Selection of healthy subjects will be performed to ensure age and sex matching.
The following procedures will be carried out as part of the research:
* Hypercapnic challenge
* PET/MRI acquisition with [18F]-CPFPX Baseline (0-70 min) Hypercapnic challenge (Breath holding) (70-100 min) Return to equilibrium (100-120 min) Receives: Procedure: 1 Hypercapnic challenge while participant is awake; Procedure: PET/MRI acquisition |
What is being measured
The primary outcome is the main question the study is designed to answer.
Comparison of the [18F]-CPFPX BPND in the brainstem structures involved in respiratory regulation under hypercapnic condition in patients with drug-resistant epilepsy with the one of healthy subjects
All analyses will be performed on Regions of Interest (ROI), defined as brainstem regions with BOLD activation during BH.
On the normalized smoothed images, an ANCOVA (analysis of covariance) will be performed, where age, gender and global non-displaceable binding potential (BPND) will be taken into account as covariates of no interest. Statistical parametric maps of the t-statistic (SPM(t)) will be calculated for two contrasts per patient (patient with drug-resistant epilepsy-heathly subjects and heathly subjects-patient with drug-resistant epilepsy) with a threshold of P<0.001 uncorrected at the voxel level; an extent threshold of 100 voxels (of 2mmx2mmx2mm) will be applied at the cluster level
Measured: Emission will be acquired over 90 minutes post-injection
Secondary outcomes (7)
Comparison of the [18F]-CPFPX BPND in the cortical structures involved in respiratory regulation under hypercapnic condition in patients with drug-resistant epilepsy with the one of healthy subjects
All analyses will be performed on Regions of Interest (ROI), defined as cortical regions with BOLD activation during BH.
On the normalized smoothed images, an ANCOVA (analysis of covariance) will be performed, where age, gender and global non-displaceable binding potential (BPND) will be taken into account as covariates of no interest. Statistical parametric maps of the t-statistic (SPM(t)) will be calculated for two contrasts per patient (patient with drug-resistant epilepsy-heathly subjects and heathly subjects-patient with drug-resistant epilepsy) with a threshold of P<0.001 uncorrected at the voxel level; an extent threshold of 100 voxels (of 2mmx2mmx2mm) will be applied at the cluster level
Measured: Emission will be acquired over 90 minutes post-injection
Evaluating the relation between [18F]-CPFPX BPND in the brainstem structures involved in respiratory regulation under hypercapnic condition and the HCVR slope in patients with drug-resistant epilepsy and in healthy subjects
HCVR measures the increase in minute ventilation (VE) induced by an increase of PETCO2. The HCVR slope, expressed in L/min/mmHg, will be calculated from the linear regression of VE and PETCO2
Measured: Emission will be acquired over 90 minutes post-injection
Comparison of the HCVR slope in patients with drug-resistant epilepsy and in heathly subjects
HCVR measures the increase in minute ventilation (VE) induced by an increase of PETCO2. The HCVR slope, expressed in L/min/mmHg, will be calculated from the linear regression of VE and PETCO2
Measured: will be measured during hypercapnic challenges between Day 15 and Day 60 after inclusion
Evaluating the relation between the HCVR slope and the pattern of BOLD activation during BH in patients with drug-resistant epilepsy and in heathly subjects
Relation between the HCVR slope and mean % change of the BOLD signal in the regions of Interest (ROI), defined as brainstem or cortical regions with BOLD activation during BH.
Measured: will be measured during fMRI acquisition (30 minutes)
Comparing brainstem regional volumes on MRI of patients with drug-resistant epilepsy with the one of healthy subjects
Gray and white matter volumes will be combined to estimate total brain volume for each subject, which will be used as a covariate in subsequent statistical modelling. Two-sample t tests will used for group comparisons in SPM (patients versus healthy subjects), with age, sex, and total brain volume as covariates. Reported P-values will be family-wise error rate (FWER)-corrected (largest cluster at P < .05). Analysis of relation between VBM and HCVR slope will used Pearson's correlation with age, sex, and total brain volume as covariates. Reported P-values will be family-wise error rate (FWER)-corrected (largest cluster at P < .05).
Measured: Will ne measured during structural MRI protocol which will include 10 minutes of anatomical imaging
Evaluating the relation between the brainstem regional volumes on MRI and the HCVR slope in patients with drug-resistant epilepsy and in heathly subjects
Analysis of relation between VBM and HCVR slope will use Pearson's correlation with age, sex, and total brain volume as covariates. Reported P-values will be family-wise error rate (FWER)-corrected (largest cluster at P < .05).
Measured: Will be measured during structural MRI protocol which will include 10 minutes of anatomical imaging
Evaluating the relation between mean daily intake of caffeine (mg/day) and the [18F]-CPFPX BPND in the brainstem and cortical structures
All analyses will be performed on Regions of Interest (ROI), defined as brainstem and cortical regions with BOLD activation during BH.
Pearson's correlation with age, sex, and global non-displaceable binding potential (BPND) as covariates
Measured: Emission will be acquired over 90 minutes post-injection
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Nov 2025
- Study start1 Oct 2026
- Primary completion1 Oct 2028 (estimated)
- Study completion1 Dec 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
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 50 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Hospices Civils de Lyon
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Sylvain RHEIMS, PUPH, Principal investigator, Hospices Civils de Lyon
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07249034
- Sponsor's protocol ID
- 2025-A01888-41
- Acronym
- BRAVE
- Status last verified
- Oct 2026
- First submitted
- 26 Sep 2025
- Last updated
- 7 Oct 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 7 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Impact of Epilepsy on the Brainstem Adenosine Pathway and Its Relation With Arousal and Respiratory Reactivity
- ClinicalTrials.gov ID
- NCT07249034
- Acronym / sponsor ID
- BRAVE / 2025-A01888-41
- Conditions
- Epilepsy, Drug-resistant Focal Epilepsy, Healthy Controls
- Keywords
- Epilepsy, adenosine pathway, respiratory reactivity, PET-MRI, [18F]CPFPX
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 50 participants (estimated)
- Lead sponsor
- Hospices Civils de LyonUniversity, hospital or other
- Study start
- 1 Oct 2026 (actual)
- Primary completion
- 1 Oct 2028 (estimated)
- Study completion
- 1 Dec 2028 (estimated)
- First posted
- 25 Nov 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.
Despite the continuous development of new antiseizure medications over the past 25 years, 30% of patients with epilepsy suffer from drug-resistant seizures and are at risk of epilepsy-related complications, like cognitive dysfunctions, sleep-disordered breathing or Sudden and Unexpected Death in Epilepsy (SUDEP). SUDEP typically occurs during sleep, after a nocturnal seizure, and primarily results from a postictal central respiratory dysfunction in patients with generalized convulsive seizure (GCS), suggesting that interaction between respiratory dysfunction and sleep state may play a role in its pathophysiology.
Post-mortem data in SUDEP patients showed alteration of neuronal populations involved in respiratory control in the medulla. Accordingly, pharmacologic strategies aimed at reducing the severity of postictal respiratory dysfunction has appeared as one of the most promising way to prevent SUDEP. However, no encouraging result has hitherto been reported.
Interconnections between the complex network that regulates arousal and sleep and the respiratory network are numerous. They primarily include the relation between chemosensitive regulation and arousal system to ensure asphyxia-induced arousal (i.e. arousal to elevated CO2), especially through serotonin (5HT)-dependent connections in brain stem. The link between alterations of the brainstem networks involved in arousal regulation and respiratory dysfunction has not been characterized in patients with epilepsy yet.
Like 5HT, adenosine is deeply implicated in the regulation of sleep and central respiratory control.
Seizures transiently increase adenosine extracellular levels. Adenosine physiological effects in the brain are mediated through the activation of two types of Adenosine receptors (ARs), A1Rs and A2ARs. Extracellular adenosine promotes sleep via A1R-dependant inhibition of glutamatergic neurons in the basal forebrain, but also via A2AR-dependant activation of neurons in the nucleus accumbens. Respiration is also inhibited by A1R and A2AR. Most importantly, it has been shown that drug-resistant epilepsy is associated with long-term alterations of ARs cortical expression. However, whether or not a similar epilepsy-related plasticity of ARs occurs in the brainstem and may participate to chronic arousal and respiratory dysfunction in epilepsy has never been investigated.
Considering the tight interplay between central respiratory control, arousal regulation and brainstem adenosine, the main hypothesis of the BRAVE study is that epilepsy might result in alterations of the distribution of A1Rs in the brainstem structures involved in respiratory regulation and/or arousal control, especially in the brainstem structures involved in respiratory regulation under hypercapnic condition.
The study combines clinical respiratory characterization, morphological, functional and metabolic imaging, using the hybrid simultaneous 3T MRI-PET scanner (Siemens Biograph mMR) of the CERMEP. Combining PET with anatomical and functional MR imaging enables non-invasively in vivo mapping of receptor binding and functional neuronal assessment of a physiological task in the entire brain with high spatial resolution.
Investigators already performed fMRI study of respiratory centers, showing number of functional changes in brainstem regions participating to the central control of respiration, including reduced activation during breath-holding fMRI, in patients with epilepsy. The BRAVE study will use the same respiratory paradigm as the one used in this past study.
PET imaging will be focused on A1R, using [18F]CPFPX, a selective A1R antagonist.
Study design
- Primary purpose
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Patients with drug-resistant epilepsy | Experimental | Procedure: 1 Hypercapnic challenge while participant is awake, Procedure: PET/MRI acquisitionDiagnosis of refractory focal epilepsy or of refractory idiopathic generalized epilepsy, as defined by the International League Against Epilepsy. The following procedures will be carried out as part of the research: * Hypercapnic challenge * PET/MRI acquisition with [18F]-CPFPX Baseline (0-70 min) Hypercapnic challenge (Breath holding) (70-100 min) Return to equilibrium (100-120 min) |
| Healthy subjects | Experimental | Procedure: 1 Hypercapnic challenge while participant is awake, Procedure: PET/MRI acquisitionSelection of healthy subjects will be performed to ensure age and sex matching. The following procedures will be carried out as part of the research: * Hypercapnic challenge * PET/MRI acquisition with [18F]-CPFPX Baseline (0-70 min) Hypercapnic challenge (Breath holding) (70-100 min) Return to equilibrium (100-120 min) |
Who may qualify
- Ages
- 18 to 55 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (11 listed)
- For patients
- For healthy volunteers
Key exclusion criteria (32 listed)
- For patients
- For healthy volunteers
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 |
|---|---|---|
| 1 Hypercapnic challenge while participant is awakeThe healthy patient/subject breathes through the mouth, using a mouthpiece and a nose clip, through a device fitted with a hermetically sealed bag that measures the various parameters of his/her breathing. At the start of the test, the healthy patient/subject breathes ambient air and his or her breathing is measured. Then, after a few minutes, the healthy patient/subject is connected to the bag, breathing in a closed circuit. This causes a gradual increase in carbon dioxide (CO2) in the inspired air. During this time, breathing parameters will be measured and gas exchanges studied with each breath. The test is stopped when the end-tidal carbon dioxide pressure (PetCO2) reaches 60 mm Hg, or in the event of intolerance | Procedure or surgery | Healthy subjects, Patients with drug-resistant epilepsy |
| PET/MRI acquisitionThe PET/MRI acquisition will be organized into 3 parts for a total duration of 120 minutes from the injection of the radiotracer 1. Baseline (0-70 min) 2. Respiratory challenge (70-100 min) : Subjects will perform three series of expiratory breath holds (six repeats during each run). A green dot will be shown for 30 seconds, indicating that the patient can still breathe normally for 30 seconds. Then, a yellow dot appears for two seconds, indicating that the patient needs to prepare himself for an expiratory BH that shall start at the end of an expiration, and at the end of the two seconds. Then a red dot appears indicating that the patient must hold his breath while being in full expiration or inspiration. The red dot remains until the patient decides to breath again and push a button to alert us of re-breathing. Screen turns black for 60 seconds before another sequence starts (30 sec. green dot). 3. Return to equilibrium (100-120 min). | Procedure or surgery | Healthy subjects, Patients with drug-resistant epilepsy |
Primary outcome
Comparison of the [18F]-CPFPX BPND in the brainstem structures involved in respiratory regulation under hypercapnic condition in patients with drug-resistant epilepsy with the one of healthy subjects
Time frame: Emission will be acquired over 90 minutes post-injection
All analyses will be performed on Regions of Interest (ROI), defined as brainstem regions with BOLD activation during BH. On the normalized smoothed images, an ANCOVA (analysis of covariance) will be performed, where age, gender and global non-displaceable binding potential (BPND) will be taken into account as covariates of no interest. Statistical parametric maps of the t-statistic (SPM(t)) will be calculated for two contrasts per patient (patient with drug-resistant epilepsy-heathly subjects and heathly subjects-patient with drug-resistant epilepsy) with a threshold of P<0.001 uncorrected at the voxel level; an extent threshold of 100 voxels (of 2mmx2mmx2mm) will be applied at the cluster level
7 secondary outcomes
Comparison of the [18F]-CPFPX BPND in the cortical structures involved in respiratory regulation under hypercapnic condition in patients with drug-resistant epilepsy with the one of healthy subjects
Time frame: Emission will be acquired over 90 minutes post-injection
Evaluating the relation between [18F]-CPFPX BPND in the brainstem structures involved in respiratory regulation under hypercapnic condition and the HCVR slope in patients with drug-resistant epilepsy and in healthy subjects
Time frame: Emission will be acquired over 90 minutes post-injection
Comparison of the HCVR slope in patients with drug-resistant epilepsy and in heathly subjects
Time frame: will be measured during hypercapnic challenges between Day 15 and Day 60 after inclusion
Evaluating the relation between the HCVR slope and the pattern of BOLD activation during BH in patients with drug-resistant epilepsy and in heathly subjects
Time frame: will be measured during fMRI acquisition (30 minutes)
Comparing brainstem regional volumes on MRI of patients with drug-resistant epilepsy with the one of healthy subjects
Time frame: Will ne measured during structural MRI protocol which will include 10 minutes of anatomical imaging
Evaluating the relation between the brainstem regional volumes on MRI and the HCVR slope in patients with drug-resistant epilepsy and in heathly subjects
Time frame: Will be measured during structural MRI protocol which will include 10 minutes of anatomical imaging
Evaluating the relation between mean daily intake of caffeine (mg/day) and the [18F]-CPFPX BPND in the brainstem and cortical structures
Time frame: Emission will be acquired over 90 minutes post-injection
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 7 Oct 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.
Sylvain RHEIMS, PUPH principal investigator
Hospices Civils de Lyon
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing 1 Hypercapnic challenge while participant is awake and PET/MRI acquisition in people with Epilepsy and Drug-resistant Focal Epilepsy, 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 11 inclusion and 32 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 7 Oct 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, PUPH (+33472357106, 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 [18F]-CPFPX BPND in the brainstem structures involved in respiratory regulation under hypercapnic condition in patients with drug-resistant epilepsy with the one of healthy subjects (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 7 Oct 2026; AzTrials last refreshed its copy on 7 Nov 2026.