A randomized, double-blind trial of triheptanoin for drug-resistant epilepsy in glucose transporter 1 deficiency syndrome.
Authors
Collins, Abigail
Horvath, Rita
Tzadok, Michal
Kay Koenig, Mary
Lacy, Adrian
Davis, Ronald
Garcia-Cazorla, Angela
Saneto, Russell P
Brandabur, Melanie
Blair, Susan
Koutsoukos, Tony
De Vivo, Darryl
Publication Date
2022-04-20Journal Title
Epilepsia
ISSN
0013-9580
Publisher
Wiley
Language
en
Type
Article
This Version
AO
VoR
Metadata
Show full item recordCitation
Striano, P., Auvin, S., Collins, A., Horvath, R., Scheffer, I. E., Tzadok, M., Miller, I., et al. (2022). A randomized, double-blind trial of triheptanoin for drug-resistant epilepsy in glucose transporter 1 deficiency syndrome.. Epilepsia https://doi.org/10.1111/epi.17263
Description
Funder: Ultragenyx Pharmaceutical Inc.; Id: http://dx.doi.org/10.13039/100013220
Abstract
OBJECTIVE: This study was undertaken to evaluate efficacy and long-term safety of triheptanoin in patients >1 year old, not on a ketogenic diet, with drug-resistant seizures associated with glucose transporter 1 deficiency syndrome (Glut1DS). METHODS: UX007G-CL201 was a randomized, double-blind, placebo-controlled trial. Following a 6-week baseline period, eligible patients were randomized 3:1 to triheptanoin or placebo. Dosing was titrated to 35% of total daily calories over 2 weeks. After an 8-week placebo-controlled period, all patients received open-label triheptanoin through Week 52. RESULTS: The study included 36 patients (15 children, 13 adolescents, eight adults). A median 12.6% reduction in overall seizure frequency was observed in the triheptanoin arm relative to baseline, and a 13.5% difference was observed relative to placebo (p = .58). In patients with absence seizures only (n = 9), a median 62.2% reduction in seizure frequency was observed in the triheptanoin arm relative to baseline. Only one patient with absence seizures only was present in the control group, preventing comparison. No statistically significant differences in seizure frequency were observed. Common treatment-emergent adverse events included diarrhea, vomiting, abdominal pain, and nausea, mostly mild or moderate in severity. No serious adverse events were considered to be treatment related. One patient discontinued due to status epilepticus. SIGNIFICANCE: Triheptanoin did not significantly reduce seizure frequency in patients with Glut1DS not on the ketogenic diet. Treatment was associated with mild to moderate gastrointestinal treatment-related events; most resolved following dose reduction or interruption and/or medication for treatment. Triheptanoin was not associated with any long-term safety concerns when administered at dose levels up to 35% of total daily caloric intake for up to 1 year.
Keywords
RESEARCH ARTICLE, RESEARCH ARTICLES, diet treatment, drug resistance, epilepsy, glucose transporter 1 deficiency syndrome, triheptanoin
Identifiers
epi17263
External DOI: https://doi.org/10.1111/epi.17263
This record's URL: https://www.repository.cam.ac.uk/handle/1810/337362
Rights
Licence:
http://creativecommons.org/licenses/by-nc/4.0/
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