Effects of oral L-carnitine administration in narcolepsy patients: a randomized, double-blind, cross-over and placebo-controlled trial.
Narcolepsy is a sleep disorder characterized by excessive daytime sleepiness, cataplexy, and rapid eye movement (REM) sleep abnormalities. A genome-wide association study (GWAS) identified a novel narcolepsy-related single nucleotide polymorphism (SNP), which is located adjacent to the carnitine palmitoyltransferase 1B (CPT1B) gene encoding an enzyme involved in β-oxidation of long-chain fatty acids. The mRNA expression levels of CPT1B were associated with this SNP. In addition, we recently reported that acylcarnitine levels were abnormally low in narcolepsy patients. To assess the efficacy of oral L-carnitine for the treatment of narcolepsy, we performed a clinical trial administering L-carnitine (510 mg/day) to patients with the disease. The study design was a randomized, double-blind, cross-over and placebo-controlled trial. Thirty narcolepsy patients were enrolled in our study. Two patients were withdrawn and 28 patients were included in the statistical analysis (15 males and 13 females, all with HLA-DQB1*06:02). L-carnitine treatment significantly improved the total time for dozing off during the daytime, calculated from the sleep logs, compared with that of placebo-treated periods. L-carnitine efficiently increased serum acylcarnitine levels, and reduced serum triglycerides concentration. Differences in the Japanese version of the Epworth Sleepiness Scale (ESS) and the Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36) vitality and mental health subscales did not reach statistical significance between L-carnitine and placebo. This study suggests that oral L-carnitine can be effective in reducing excessive daytime sleepiness in narcolepsy patients.


BACKGROUND
University hospital Medical Information Network (UMIN) UMIN000003760.
Department of Human Genetics, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
Taku
T
Miyagawa
Hiromi
H
Kawamura
Mariko
M
Obuchi
Asuka
A
Ikesaki
Akiko
A
Ozaki
Katsushi
K
Tokunaga
Yuichi
Y
Inoue
Makoto
M
Honda
D000284:Administration, Oral; D000328:Adult; D002331:Carnitine / Q000008:administration & dosage* / Q000494:pharmacology / Q000627:therapeutic use*; D018592:Cross-Over Studies; D004311:Double-Blind Method; D005227:Fatty Acids / Q000378:metabolism; D005260:Female; D006801:Humans; D008297:Male; D009290:Narcolepsy / Q000188:drug therapy* / Q000378:metabolism; D010084:Oxidation-Reduction / Q000187:drug effects; D010919:Placebos
D005227:Fatty Acids; D010919:Placebos; D002331:Carnitine