NCT07249034: BRAVE

Impact of Epilepsy on the Brainstem Adenosine Pathway and Its Relation With Arousal and Respiratory Reactivity

Not yet recruiting NA Last updated 25 November 2025

What this trial tests

NA trial testing 1 Hypercapnic challenge while participant is awake in Epilepsy in 50 participants. Not yet recruiting.

Timeline

1 January 2026

Primary endpoint
1 January 2028

1 March 2028

Quick facts

Lead sponsor	Hospices Civils de Lyon
Phase	NA
Status	Not yet recruiting
Study type	INTERVENTIONAL
Allocation	non randomized
Design	parallel
Masking	none
Primary purpose	basic science
Enrollment	50
Start date	1 January 2026
Primary completion	1 January 2028
Estimated completion	1 March 2028
Sites	1 location across France

Drugs / interventions tested

• 1 Hypercapnic challenge while participant is awake
• PET/MRI acquisition

Conditions studied

• Epilepsy — all drugs for Epilepsy →
• Drug-resistant Focal Epilepsy — all drugs for Drug-resistant Focal Epilepsy →
• Healthy Controls — all drugs for Healthy Controls →

Sponsor

Hospices Civils de Lyon — full company profile →

Who can join

Adults 18 to 55, any sex, with Epilepsy or Drug-resistant Focal Epilepsy. Patients with the condition only — healthy volunteers not accepted.

Sponsor's own description

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.

Publications & conference data

No peer-reviewed publications indexed yet for this trial.