Randomized trial of add-on triheptanoin vs medium chain triglycerides in adults with refractory epilepsy.

ABSTRACT

OBJECTIVE: To investigate the feasibility, safety, and tolerability of add-on treatment of the triglycerides of heptanoate (triheptanoin) vs the triglycerides of octanoate and decanoate (medium chain triglycerides [MCTs]) in adults with treatment-refractory epilepsy. METHODS: After an 8-week prospective baseline period, people with drug-resistant epilepsy were randomized in a double-blind fashion to receive triheptanoin or MCTs. Treatment was titrated over 3 weeks to a maximum of 100 mL/d to be distributed over 3 meals and mixed into food, followed by 12-week maintenance before tapering. The primary aims were to assess the following (a) safety by comparing the number of intervention-related adverse events with triheptanoin vs MCT treatment and (b) adherence, measured as a percentage of the prescribed treatment doses taken. RESULTS: Thirty-four people were randomized (17 to MCT and 17 to triheptanoin). There were no differences regarding (a) the number of participants completing the study (11 vs 9 participants), (b) the time until withdrawal, (c) the total number of adverse events or those potentially related to treatment, (d) median doses of oils taken (59 vs 55 mL/d, P = 0.59), or (e) change in seizure frequency (54% vs 102%, P = 0.13). Please note that people with focal unaware seizures were underrepresented in the triheptanoin treatment arm (P = 0.04). The most common adverse events were gastrointestinal disturbances (47% and 62.5% of participants). Five people taking on average 0.73 mL/kg body weight MCTs (0.64 mL/kg median) and one person taking 0.59 mL/kg triheptanoin showed >50% reduction in seizure frequency, specifically focal unaware seizures. SIGNIFICANCE: Add-on treatment with MCTs or triheptanoin was feasible, safe, and tolerated for 12 weeks in two-thirds of people with treatment-resistant epilepsy. Our results indicate a protective effect of MCTs on focal unaware seizures. This warrants further study.