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| ID | Type | Description | Link |
|---|---|---|---|
| 2025-523608-64-00 | EU Trial (CTIS) Number |
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Epilepsy is one of the most common neurological disorders, with one of the highest morbidity rates of all diseases. Despite the development of new anticonvulsant drugs, around a third of patients suffer from drug-resistant epilepsy (RPE). The onset of RPE can be lengthy, prolonging the period during which affected patients live with seizures that have a negative impact on their quality of life. Epilepsy surgery can be a curative treatment, and can enable anticonvulsant medication to be discontinued, optimizing quality of life and cognitive development. In addition, as it has been shown that the prolonged duration of epilepsy prior to surgery has an impact on the occurrence of postoperative seizures, early surgery is increasingly being considered. Focal cortical dysplasia (FCD) is the leading cause of focal lesional epilepsy and is generally drug-resistant. Good postoperative seizure results after surgical resection are strongly linked to complete resection of the dysplastic tissue. Consequently, accurate localization and precise delineation of FCD lesions are crucial during surgery. Currently, the extent of surgical resection is based primarily on preoperative examination, as the macroscopic appearance of dysplastic tissue does not differ from normal cortex. The various intraoperative techniques available to improve the quality of excision (neuronavigation, ultrasound, intraoperative MRI and intraoperative guidance by fluorescence microscopy) all have their limitations. In this context, new intraoperative tools are needed to help the neurosurgeon delineate lesions during surgery. Intraoperative fluorescence spectroscopy is used for surgical guidance of gliomas and other brain pathologies, and has demonstrated its ability to characterize pathological tissues. DCFs exhibit metabolic differences that can also be detected by 5-amino-levulinic acid (5-ALA)-induced protoporphyrin IX (PpIX) fluorescence intraoperatively. Indeed, in some patients who underwent surgery after a diagnosis of glioma, fluorescence was observed even though histological analysis classified the excised tissue as DCF. What's more, glioma and DCF share a common feature: the mitochondria of affected cells are deficient in complex IV. Cytochrome c oxidase (CCO) is largely involved in mitochondrial complex IV, and NAD is a central metabolite involved in redox reactions within cells. Both metabolites (CCO and NAD) can be visualized intraoperatively by optical and fluorescence spectroscopy.
FLUOFOCODYS is a prospective, non-comparative, single-center, human drug pilot clinical trial. 5 patients will be included.
Primary objective of FLUOFOCODYS study is to measure the fluorescence of biomarkers of focal epileptic lesions by intraoperative fluorescence spectroscopy.
The secondary objectives are as follows:
The hypothesis of this project is that intraoperative fluorescence spectroscopy could robustly measure 5-ALA-induced protoporphyrin IX fluorescence in FCD and could ultimately aid FCD surgery. Thus, to understand intraoperative biomarker fluorescence spectroscopy in DCF, preoperative MRI and postoperative histology are crucial. This will enable MRI-informed intraoperative fluorescence spectroscopy. These comparative measurements will be completed with SpiderMass technology (metabo-lipidomic mass spectrometry). The effectiveness of intraoperative tools could therefore be assessed prior to surgery, which could have an impact on the therapeutic decision to proceed with surgery.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 5-ALA (Gliolan) | Experimental | Children and adults with drug resistant epilepsy, related to a probable FCD and with surgical indication validated by the epileptic multi-disciplinary staff meeting will receive the study treatment (5-ALA) orally at a dose of 20mg/kg |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| 5-ALA (Gliolan) | Drug | Patients will be given 5-ALA (20 mg per kilogram body weight) before the surgery, between 2 and 4 hours before anaesthesia. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Concentration of fluorescent compound (in mol/L) during the chirurgical intervention on the extracted tissue sample of FCD | Measure of biomarkers fluorescence of focal epileptic lesion by intraoperative fluorescence spectroscopy. | Day 0 |
| Measure | Description | Time Frame |
|---|---|---|
| FCD volume in mm3 on standard MRI | Compare FCD volume between High Resolution-MultiModal-MRI and standard MRI. | 60 days before Day 0 (=surgery) |
| FCD volume in mm3 on High Resolution MM- MRI | Compare FCD volume between High Resolution-MultiModal-MRI and standard MRI. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Pierre-Aurélien BEURIAT, MD | Contact | 4 27 85 62 20 | +33 | pierre-aurelien.beuriat@chu-lyon.fr |
| Clarisse SAUNIER | Contact | 4 27 85 62 64 | +33 | clarisse.saunier@chu-lyon.fr |
| Name | Affiliation | Role |
|---|---|---|
| Pierre-Aurélien BEURIAT | Hospices Civils de Lyon | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Hôpital Neurologique Pierre Wertheimer - Groupement Hospitalier Est - Hospices Civils de Lyon | Bron | 69500 | France |
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| ID | Term |
|---|---|
| D000069279 | Drug Resistant Epilepsy |
| D004827 | Epilepsy |
| D000092222 | Focal Cortical Dysplasia |
| ID | Term |
|---|---|
| D001927 | Brain Diseases |
| D002493 | Central Nervous System Diseases |
| D009422 | Nervous System Diseases |
| D065703 | Malformations of Cortical Development, Group I |
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This is a pilot, prospective, non-comparative and monocentric clinical drug trial on medicinal product for human use.
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| Day 0 (=surgery) |
| Index kappa concordance of the volume in mm3 of focal cortical dysplasia measured by standard MRI | Evaluation of the concordance of FCD measurements between HR-MM-MRI and standard MRI | 60 days before day 0 |
| Index kappa concordance of the volume in mm3 of focal cortical dysplasia measured by HR MM-MRI | Evaluation of the concordance of FCD measurements between HR-MM-MRI and standard MRI | Day 0 |
| Concentration measured by fluorescence spectroscopy on extracted tissue sample of FCD | Evaluation of correlation between fluorescence spectroscopy measurements and Spidermass measurements on extracted tissue sample of FCD. | Day 0 |
| Relative concentration of molecular species measured by SpiderMass on extracted tissue sample of FCD | Evaluation of correlation between fluorescence spectroscopy measurements and Spidermass measurements on extracted tissue sample of FCD. | Day 0 |
| Number of adverse events | Description of any Adverse Events that have occurred after the experimental treatment until end of study participation | From the enrollment to day 1 |
| Hôpital Femme Mère Enfant - Groupement Hospitalier Est - Hospices Civils de Lyon | Bron | France |
|
| D054220 | Malformations of Cortical Development |
| D009421 | Nervous System Malformations |
| D000013 | Congenital Abnormalities |
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |