Fenofibrate as adjuvant therapy in persons with active epilepsy: A double-blind, randomized, placebo-controlled trial

This study aimed to assess efficacy and safety of fenofibrate as adjuvant therapy on seizure control and epileptogenic biomarkers in persons with active epilepsy(a-PWE). This single-center randomized, double-blind, placebo-controlled, parallel-group trial was conducted over 6 months. a-PWE (n = 80, 40 in each group) who have ≥ 2 seizures in preceding 3 months despite receiving ≥ 2 antiseizure medications (ASMs) were randomly assigned to receive fenofibrate (145 mg orally once daily) or matching placebo adjuvant to ongoing ASMs with 3 and 6-month follow-ups. Primary outcome: percentage change in monthly seizure frequency from baseline to 6-months. Secondary outcomes: 50% responder rate, epileptogenic biomarkers (total antioxidant capacity, neurotrophin-3, high mobility group box-1), quality of life, and safety parameters. The percentage change in monthly seizure frequency (primary outcome) was significantly higher in fenofibrate {median [Inter quartile range] 57.50(4.30 to 75)} compared to the placebo [-40.20(-60.92 to 39.60)]; [median estimate with 95% confidence interval: 70 (34.60 to 102.50), (p < 0.001)] as per intention-to-treat analysis. Similarly, 50% responder rate was significantly higher in the fenofibrate group compared to placebo (60% vs. 22.5%, p = 0.001). Epileptogenic biomarkers showed no any significant difference across groups except for TAC, which increased significantly in fenofibrate compared to placebo (p = 0.01). Fenofibrate was well tolerated without any serious adverse events. Fenofibrate added to ASMs improved seizure control and TAC in a-PWE compared to placebo, suggesting potential therapeutic role in epilepsy. Clinical trials registry India: CTRI/2021/03/032317, date March 25, 2021.