[18F]CPFPX PET Assessment of Brainstem Adenosine A1 Receptor Distribution in Drug-Resistant Epilepsy Under Hypercapnic Challenge
- Trial ID
- 2025-524511-36-00
- Protocol
- 69HCL25_0757
- Sponsor
- Hospices Civils De Lyon
Trial statistics
Diseases & Conditions
Objectives
The primary objective of this study is to compare the distribution of A1Rs in the brainstem structures involved in respiratory regulation under hypercapnic conditions between patients with drug-resistant epilepsy and healthy subjects using [18F]-CPFPX PET. This investigation aims to characterize the impact of epilepsy on the brainstem adenosine pathway and its subsequent relationship with arousal and respiratory reactivity. 1: Diagnosis.
The secondary objectives include:
- Comparing the distribution of A1Rs in cortical structures involved in respiratory regulation under hypercapnic conditions via [18F]-CPFPX PET.
- Evaluating the correlation between A1R distribution in brainstem structures and inter-ictal respiratory functioning, specifically hypercapnic ventilatory response (HCVR) alterations.
- Comparing the awake HCVR between patients with drug-resistant epilepsy and healthy subjects.
- Assessing the relationship between awake HCVR and the structures involved in respiratory regulation under hypercapnic conditions.
- Comparing regional brainstem volumes via MRI in the study populations.
- Evaluating the correlation between regional brainstem volumes on MRI and awake HCVR.
- Analyzing the relationship between habitual caffeine consumption and the distribution of A1Rs in the brainstem and cortex.
Participants
The sponsor did not provide information regarding the total number of participants. The study population consists of both healthy volunteers and patients diagnosed with drug-resistant epilepsy. The cohort includes both males and females within the age range of 18 to 55 years. Eligible patients must have a diagnosis of focal epilepsy or idiopathic generalized epilepsy. Inclusion requires a history of at least three focal to bilateral tonic-clonic seizures or generalized tonic-clonic seizures during the preceding 18 months. The patient population is defined by the failure to achieve seizure freedom following adequate trials of two tolerated and appropriately selected antiseizure drug schedules. For participants of childbearing potential, the use of highly effective contraception is required until the end of relevant systemic exposure.
Plans and Procedures
This Phase II clinical trial aims to compare the distribution of adenosine A1 receptors (A1Rs) in brainstem structures involved in respiratory regulation under hypercapnic conditions between patients with drug-resistant epilepsy and healthy subjects. The study utilizes [18F]CPFPX, administered as a solution for injection at a dose of 275 MBq, for Positron Emission Tomography (PET) imaging to determine the binding potential (BPND). Research methodology involves assessing the relationship between receptor density and the hypercapnic ventilatory response (HCVR) slope, as well as BOLD activation patterns during hyperventilation. Secondary objectives include comparing cortical structure BPND, brainstem regional volumes via MRI, and evaluating the impact of daily caffeine intake on receptor distribution. The study involves a screening process to confirm eligibility based on age, seizure history, and medical diagnosis, followed by study visits including systemic exposure assessment. Participation ends upon completion of relevant clinical evaluations. The estimated recruitment period for the study is from March 2026 to May 2028.
Treatment
The experimental agent is [18F]CPFPX, which is administered as a solution for injection. The dose administered is 275 MBq via injection. This substance is used for Positron Emission Tomography (PET) imaging to evaluate the distribution of adenosine A1 receptors (A1Rs) within the brainstem structures. The study focuses on the assessment of these receptors in relation to respiratory regulation during hypercapnia in patients diagnosed with drug-resistant epilepsy.
Efficacy
Efficacy assessment in this study focuses on the distribution of adenosine A1 receptors (A1Rs) within specific neuroanatomical regions. The primary endpoint involves the comparison of [18F]-CPFPX BPND in brainstem structures involved in respiratory regulation under hypercapnic conditions between patients with drug-resistant epilepsy and healthy subjects.
Secondary endpoints include:
- Comparison of [18F]-CPFPX BPND in cortical structures involved in respiratory regulation under hypercapnic conditions.
- Evaluation of the relationship between [18F]-CPFPX BPND in brainstem structures and the hypercapnic ventilatory response (HCVR) slope.
- Comparison of the HCVR slope between the study populations.
- Evaluation of the relationship between the HCVR slope and the pattern of blood-oxygen-level-dependent (BOLD) activation during hyperventilation (BH).
- Comparison of brainstem regional volumes via magnetic resonance imaging (MRI).
- Evaluation of the relationship between brainstem regional volumes and the HCVR slope.
- Evaluation of the relationship between mean daily caffeine intake and [18F]-CPFPX BPND in brainstem and cortical structures.
Inclusion and Exclusion Criteria
Inclusion Criteria
- Patient : Written informed consent obtained from study subject and ability for study subject to comply with the requirements of the study
- Patient : Aged 18 to 55 years old
- Patient : Diagnosis of focal epilepsy or of idiopathic generalized epilepsy, as defined by the International League Against Epilepsy
- 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
- Patient : Patients with ≥3 focal to bilateral tonic-clonic seizure (FBTCS) or generalized tonic-clonic seizure (GTCS) during the past 18 months
- Patient : For women of able to procreate , use highly effective contraception until the end of relevant systemic exposure (V2)
- Healthy subjects : Written informed consent obtained from study subject and ability for study subject to comply with the requirements of the study
- Healthy subjects : Aged 18 to 55 years old
- Healthy subjects : For women of childbearing potential, use highly effective contraception until the end of relevant systemic exposure (V2)
Exclusion Criteria
- 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
- Patient :Adults subject to a legal protection measure (guardianship, curatorship)
- Patient : Persons not affiliated to a social security scheme or beneficiaries of a similar scheme
- Patient :Hypersensitivity to [18F]-CPFPX
- Healthy subject : History of epilepsy
- 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
- 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
- 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
- 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)
- Healthy subject : MRI contra-indication (presence of metallic elements, claustrophobia)
- Healthy subject : Pregnant women, women in labor or breastfeeding women based on declarations at V0
- 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
- Healthy subject : Patients suffering from a psychiatric disorder, regardless of its etiology, whose care is provided under compulsory measures
- Healthy subject : Persons deprived of their liberty by a judicial or administrative decision
- Healthy subject : Adults subject to a legal protection measure (guardianship, curatorship)
- Healthy subject : Persons not affiliated to a social security scheme or beneficiaries of a similar scheme
- Healthy subject : Hypersensitivity to [18F]-CPFPX
- 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)
- Patient : MRI contra-indication (presence of metallic elements, claustrophobia)
- Patient : Patient treated with vagal nerve stimulation or deep brain stimulation
- Patient : Pregnant women, women in labor or breastfeeding women based on declarations at V0
- Patient : Patients suffering from a psychiatric disorder, regardless of its etiology, whose care is provided under compulsory measures
- Patient :Persons deprived of their liberty by a judicial or administrative decision
- 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
- Patient : ischaemic heart disease defined as history of myocardial ischemia and/or of typical angina confirmed by a cardiologist.
- 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
- Patient : Positive urine pregnancy test at V2, if applicable
- 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
- Healthy Subject : Ischaemic heart disease defined as history of myocardial ischemia and/or of typical angina confirmed by a cardiologist.
- Healthy Subject : Positive urine pregnancy test at V2, if applicable
Trial Status by Country
| Country | Status | Start of Recruitment | Planned Patients |
|---|---|---|---|
 France | Not Yet Recruiting | 01 Mar 2026 | 50 |
Sites & Investigators
Research sites
Investigators
Investigational Products
Details about the medicinal products being studied in this clinical trial.
| Product Name | Role in Trial | Formulation | Administration | Max Daily Dose | Treatment Duration | EU MP Number |
|---|---|---|---|---|---|---|
[18F]CPFPX | Test | SOLUTION FOR INJECTION | INJECTION | 275 | 1 | PRD13157054 |