Efficacy of Probenecid on Cluster Seizures During Anti Seizure Medication Withdrawal in Presurgical Focal Epilepsy Video-EEG Monitoring (PROBCLUSTER)

Fondation Ophtalmologique Adolphe de Rothschild

Status and phase: Not yet enrolling; Phase 2

Conditions: Focal Epilepsy

Treatments: Drug: Probenecid; Other: Placebo

Study type: Interventional

Funder types: NETWORK

Identifiers

NCT07318870

GHD_2024_12

Details and patient eligibility

About

ProbCluster trial aims at making the proof of concept of antiseizure efficacy of the old antigout PBN in SC, in which Panx1 involvement is relevant on SC pathophysiology and in which efficient therapies are still lacking. The trial will be performed on patients with focal epilepsy in presurgical evaluation undergoing video-EEG monitoring, a setting characterized by a high risk of SC and an efficient video-EEG monitoring of seizures, reducing the risk of erroneous report based on patient home assessment. PBN is a good candidate for a repurposing in epilepsy, due to its brain penetration allowing Panx1 in situ blockade and of its good security profile. The repurposing process allows a faster, safer and cheaper development.

Enrollment: 600 estimated patients

Sex: All

Ages: 6 to 50 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Patients between 6 and 50 years old
• weighting > 20 kg
• With focal seizures epilepsy
• Requiring video-EEG recording in Epilepsy Monitoring Units (EMU) for the presurgical evaluation of a focal epilepsy, with planned ASM withdrawal in order to precipitate seizure occurrence
• Able to take an oral therapy
• Ability to record the patient > 12 hours after the second seizure of the cluster
• Having received informed information about the study and having signed a consent form to participate in the study. Written consent of both holders of parental authority for minor patients.

Exclusion criteria

• Hypersensitivity to PBN or to any of the excipients (Microcrystalline cellulose, Hypromellose, Sodium carboxymethylamidon, Colloidal anhydrous silica, Magnesium stearate)
• Impaired renal function (creatinine clearance < 50 mL/min)
• Lithiasis diathesis
• Treatment by the following drugs: penicillins cephalosporins, acetylsalicylic acid, methotrexate, acetaminophen, naproxen, indomethacin, ketoprofen, meclofenamate, lorazepam, rifampicin, acyclovir, ganciclovir and zidovudine, sulfonamide, dyprophylline
• Acute gout attack
• Hyperuricemia secondary to cancer chemotherapy, radiotherapy or myeloproliferative neoplasia
• Primary hyperuricemia due to overproduction of uric acid.
• Pregnant or breast-feeding woman
• Patient benefiting from legal protection

Secondary exclusion criteria (before randomization) :

- Patient not randomized: Not experiencing at least 2 seizures lasting less than 10 minutes in 6 hours or less period (defining a SC) during the video-EEG monitoring period OR having no seizure recorded before the cluster.

Patients secondarily excluded will be excluded before randomization and will be replaced.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

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600 participants in 2 patient groups, including a placebo group

probenecid

Experimental group

Description:

Oral administration of PBN at a dose of 3g in adults or children weighting \> 50 kg; at a dose of 2g in children weighting 35 to 50 kg; and at a dose of 1g in children weighting 20 to 34 kg.

Treatment:

Drug: Probenecid

placebo

Placebo Comparator group

Description:

Placebo administration in a scheme similar to experimental treatment.

Treatment:

Other: Placebo