A pilot study of add-on oral triheptanoin treatment for children with medically refractory epilepsy

Despite antiepileptic medication and dietary treatment options available about 45% of children with epilepsy still suffer from uncontrolled seizures. Triheptanoin is an anaplerotic treatment designed to improve energy generation via the Krebs cycle. For the first time, we evaluated the feasibility, tolerability and efficacy of add-on triheptanoin in 12 patients with medically refractory epilepsy (seven males, five females; min–max: 3–18yr, median 13.5 yr). Eight out of a total of 12 children (67%), who tested the treatment, finished the trial and tolerated between 30 and 100 ml of triheptanoin per day for >12 weeks (median 55 ml, 20.5% caloric intake). The most common adverse effects were diarrhea and other gastro-intestinal effects in seven kids. One child experienced leaking and another child had an infected percutaneous endoscopic gastrostomy button. Five children (62.5%), who all had been on the ketogenic diet previously, showed sustained >50% reductions in seizure frequency, including one patient who became seizure free for 30 weeks. Four patients extended their treatment to a total of 201–909 days, until seizure frequency or severity increased. In this small trial, triheptanoin was safe and tolerable in children with epilepsy. As some children showed reductions in seizure numbers and/or severity, larger randomized controlled studies are now needed for further evaluation of safety and efficacy. •Triheptanoin add-on treatment (30–100 ml/day) is feasible in children with epilepsy.•There were mostly non-serious adverse effects, including GI problems (7 of 12 kids).•Reductions in seizure frequencies in 5 of 8 children (62.5%) during treatment phase.•Further studies of triheptanoin in epilepsy are warranted.