Impact of epilepsy on the brainstem adenosine pathway and its relation with arousal and respiratory reactivity BRAVE

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Hospices Civils De Lyon

Participant type

Healthy volunteers, Patients

Age range

18-64 years

Gender

Male and Female

Therapeutic area

Diseases [C] - Nervous System Diseases [C10]

Decision date (initial)

2026-04-30

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

European Research Council

External identifiers

EU CT number

2025-524511-36-00

ClinicalTrials.gov

NCT07249034

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Diagnosis

Comparing with [18F]-CPFPX PET the distribution of A1Rs in the brainstem structures involved in respiratory regulation under hypercapnic condition in patients with drug-resistant epilepsy with the one of healthy subjects.

Secondary objectives 7

1. Comparing with [18F]-CPFPX PET the distribution of A1Rs in the cortical structures involved in respiratory regulation under hypercapnic condition in patients with drug-resistant epilepsy with the one of healthy subjects
2. Evaluating with [18F]-CPFPX PET the relation between distribution of A1Rs in the brainstem structures involved in respiratory regulation under hypercapnic condition and inter-ictal respiratory functioning defined as alterations of hypercapnic ventilatory response (HCVR) in patients with drug-resistant epilepsy with the one of healthy subjects
3. Comparing the HCVR awake in patients with drug-resistant epilepsy and in heathly subjects
4. Evaluating the relation between the HCVR awake and the structures involved in respiratory regulation under hypercapnic condition
5. Comparing brainstem regional volumes on MRI of patients with drug-resistant epilepsy with the one of healthy subjects
6. Evaluating the relation between the brainstem regional volumes on MRI and HCVR awake in patients with drug-resistant epilepsy and in heathly subjects
7. Evaluating the relation between usual caffeine consumption* and distribution of A1Rs in the brainstem and the cortex in patients with drug-resistant epilepsy with the one of healthy subjects

Conditions and MedDRA coding

Neurology

Study design 1 period

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 9

1. Patient : Written informed consent obtained from study subject and ability for study subject to comply with the requirements of the study
2. Patient : Aged 18 to 55 years old
3. Patient : Diagnosis of focal epilepsy or of idiopathic generalized epilepsy, as defined by the International League Against Epilepsy
4. Patient : 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 freedom52
5. Patient : Patients with ≥3 focal to bilateral tonic-clonic seizure (FBTCS) or generalized tonic-clonic seizure (GTCS) during the past 18 months
6. Patient : For women of able to procreate , use highly effective contraception until the end of relevant systemic exposure (V2)
7. Healthy subjects : Written informed consent obtained from study subject and ability for study subject to comply with the requirements of the study
8. Healthy subjects : Aged 18 to 55 years old
9. Healthy subjects : For women of childbearing potential, use highly effective contraception until the end of relevant systemic exposure (V2)

Exclusion criteria 30

1. Patient : 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
2. Patient :Adults subject to a legal protection measure (guardianship, curatorship)
3. Patient : Persons not affiliated to a social security scheme or beneficiaries of a similar scheme
4. Patient :Hypersensitivity to [18F]-CPFPX
5. Healthy subject : History of epilepsy
6. Healthy subject : 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
7. Healthy subject : 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
8. Healthy subject : 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
9. Healthy subject : 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)
10. Healthy subject : MRI contra-indication (presence of metallic elements, claustrophobia)
11. Healthy subject : Pregnant women, women in labor or breastfeeding women based on declarations at V0
12. Patient : 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
13. Healthy subject : Patients suffering from a psychiatric disorder, regardless of its etiology, whose care is provided under compulsory measures
14. Healthy subject : Persons deprived of their liberty by a judicial or administrative decision
15. Healthy subject : Adults subject to a legal protection measure (guardianship, curatorship)
16. Healthy subject : Persons not affiliated to a social security scheme or beneficiaries of a similar scheme
17. Healthy subject : Hypersensitivity to [18F]-CPFPX
18. Patient : 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)
19. Patient : MRI contra-indication (presence of metallic elements, claustrophobia)
20. Patient : Patient treated with vagal nerve stimulation or deep brain stimulation
21. Patient : Pregnant women, women in labor or breastfeeding women based on declarations at V0
22. Patient : Patients suffering from a psychiatric disorder, regardless of its etiology, whose care is provided under compulsory measures
23. Patient :Persons deprived of their liberty by a judicial or administrative decision
24. Patient : 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
25. Patient : ischaemic heart disease defined as history of myocardial ischemia and/or of typical angina confirmed by a cardiologist.
26. PAtient : 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
27. Patient : Positive urine pregnancy test at V2, if applicable
28. Healthy subject : 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
29. Healthy Subject : Ischaemic heart disease defined as history of myocardial ischemia and/or of typical angina confirmed by a cardiologist.
30. Healthy Subject : Positive urine pregnancy test at V2, if applicable

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. 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

Secondary endpoints 7

1. 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
2. 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
3. Comparison of the HCVR slope in patients with drug-resistant epilepsy and in heathly subjects
4. Evaluating the relation between the HCVR slope and the pattern of BOLD activiation during BH in patients with drug-resistant epilepsy and in heathly subjects
5. Comparing brainstem regional volumes on MRI of patients with drug-resistant epilepsy with the one of healthy subjects
6. Evaluating the relation between the brainstem regional volumes on MRI and the HCVR slope in patients with drug-resistant epilepsy and in heathly subjects
7. Evaluating the relation between mean daily intake of caffeine (mg/day) and the [18F]-CPFPX BPND in the brainstem and cortical structures

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Hospices Civils De Lyon

Sponsor organisation

Hospices Civils De Lyon

Address

3 Quai Des Celestins, Bp 2251 Bp 2251

City

Lyon Cedex 02

Postcode

69229

Country

France

Scientific contact point

Organisation

Hospices Civils De Lyon

Contact name

Pr Sylvain RHEIMS

Public contact point

Organisation

Hospices Civils De Lyon

Contact name

Pr Sylvain RHEIMS

Locations

1 EU/EEA country · 1 investigational sites

By country

Investigational sites

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 15 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

1 submissions — initial application plus substantial / non-substantial modifications