Table 2.

Currently active registered clinical trials investigating targeted therapy in epilepsy related to MCDs

Clinical trial number	Phase	Study title	Aims	Primary outcome measures
NCT02962414	III	Roll-over Study to Collect and Assess Long-term Safety of Everolimus in Patients With TSC and Refractory Seizures Who Have Completed the EXIST-3 Study [CRAD001M2304] and Who Are Benefitting From Continued Treatment	Evaluate long-term safety in patients with TSC and refractory seizures in the EXIST-3 trial who are continuing to be treated with and benefitting from treatment with everolimus (enrollment 206 participants)	Adverse events and serious adverse events (10 years)
NCT04595513	I/II	Stopping TSC Onset and Progression 2: Epilepsy Prevention in TSC Infants (STOP2)	Open label phase to verify sirolimus dosing ➔ randomized, double-blind, placebo-controlled phase to evaluate safety and efficacy of early sirolimus to prevent or delay seizure onset in infants (up to 6 months old at enrollment) with TSC (estimated enrollment 65 participants)	1) Percentage of subjects reporting severe adverse event or serious adverse event 2) Time to seizure onset
NCT02451696	II	A Pilot Study To Evaluate The Effects of Everolimus on Brain mTOR Activity and Cortical Hyperexcitability in TSC and FCD	Evaluate the effects of everolimus on brain mTOR signaling in patients (aged 1–40 years at enrollment) with FCD or TSC and refractory epilepsy who are having brain surgery (enrolled 15 participants)	Number of patients with adverse events
NCT03198949	II	A Study Investigating the Anti-epileptic Efficacy of Afinitor (Everolimus) in Patients With Refractory Seizures Who Have Focal Cortical Dysplasia Type II	Randomized, double-blind, placebo-controlled cross over study to evaluate the efficacy and safety of everolimus in patients (aged 4–40 years at enrollment) with FCD II who have failed more than 2 AEDs and surgery (enrolled 23 participants)	Number of patients with at least 50% seizure reduction
NCT02849457	II	Preventing Epilepsy Using Vigabatrin In Infants With Tuberous Sclerosis Complex*	Randomized, double-blind, placebo-controlled study to evaluate the impact of early identification of EEG biomarkers and early treatment with vigabatrin in infants (up to 6 months at enrollment) with TSC (enrolled 84 participants)	Cognitive assessment scores on the Bayley Scales of Infant and Toddler Development at 24 months

^*Further studies needed to determine if vigabatrin is a true targeted therapy