Rationale:
Approximately 30% of persons with idiopathic generalized epilepsy (IGE) are resistant to antiseizure medications (ASMs). There are no options for a surgical or ablative procedure to reduce seizure frequency, nor is there an FDA approved neuromodulation therapy.
FDA granted a Breakthrough Device Designation to study the RNS System treatment of ASM-resistant IGE with bilateral stimulation of the CM nucleus of the thalamus. NAUTILUS is a randomized controlled trial (RCT; NCT05147571) to evaluate whether the RNS System could provide a safe and effective long-term treatment for persons with ASM-resistant IGE and GTCs. Preliminary safety and effectiveness results to 12 months of responsive stimulation therapy are provided here.
Methods:
Participants were recruited from 23 sites. All patients had IGE and GTCs, with or without myoclonic and absence seizures. GTCs were selected for the effectiveness endpoint because they can be reliably counted and are associated with the highest risk for injury and SUDEP.
Participants were required to have ≥ 2 GTCs over a combined retrospective and prospective baseline. Detection was enabled at implantation of the RNS neurostimulator and depth leads in the left and right CM. Participants were randomized one month later to active or sham stimulation. The effectiveness evaluation period started at the fourth month and lasted until the second GTC was reported.
The primary safety endpoint was the % of participants with serious adverse device events at 12 weeks post-implant. The primary effectiveness endpoint was time-to-event (second GTC). Secondary and additional endpoints included days with GTCs or any type of generalized seizure, % reduction in GTCs, quality of life, and global impression of change.
Results:
Eighty-seven patients were implanted and 84 completed 12 months. Participant characteristics are provided in Table 1. There was a high variance in baseline frequency of GTCs and in days with any generalized seizures.
The primary safety endpoint was met (p < 0.0001), and stimulation was well-tolerated.