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

Aim: 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. Method: 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). Results: 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. Interpretation: 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.