Effect of sodium oxybate on brown adipose tissue activity in narcolepsy

From as early as the 1930s, it has been reported that obesity is more prevalent
in patients with the sleep-wake disorder narcolepsy than in healthy controls.
Recent observations show that narcolepsy type 1 patients lose weight when using
sodium oxybate (SXB). A mean loss of 5.1 kg has been reported in several
studies. The underlying mechanism is unclear. Based on the available animal
studies and one human study that shows an increase in sympathetic activity
after SXB administration [4], we hypothesize that activation of
energy-combusting brown adipose tissue (BAT) via enhanced sympathetic
innervation by SXB might be crucial in mediating the weight loss in narcolepsy
type 1 patients after initiation of SXB treatment.

Primary objective:
1. To assess the effect of SXB treatment on cold-induced BAT volume and
activity in narcolepsy type 1 patients.

Secondary objectives:
1. To assess the effect of SXB treatment on thermoneutral BAT volume and fat
fraction, lipoprotein dynamics, resting energy expenditure and skin temperature
in narcolepsy type 1 patients.
2. To assess differences in cold-induced BAT volume and activity, thermoneutral
BAT volume and fat fraction, resting energy expenditure, skin temperature and
cold-induced lipoprotein dynamics between narcolepsy type 1 patients and
healthy controls.
3. To correlate weight and fat/lean mass loss in narcolepsy type 1 upon SXB
treatment initiation with observed BAT activity changes.

Prospective observational study.

The 18F-FDG tracer that is used in the 18F-FDG PET-CT-scan for brown adipose
tissue measurement is radioactive. The end-products of metabolizing this tracer
are not. All radioactivity of 18F-FDG decays with a half-life of 110 minutes
(just under 2 hours). Thus, within 24 hours (13 half-lives), the radioactivity
in the patient and in any initially voided urine after the PET exam, will have
decayed to 2*13 = 1/8192 of the initial radioactivity of the dose. In this
study, 74 MBq 18F-FDG will be administered intravenously. Using a conversion
factor of 1.9x10-2 mSv/MBq, this amounts to an effective radiation dose of 1.40
mSv. A low dose CT scan (30 mA) will be used for attenuation correction and
localization of the 18F-FDG uptake sites, with an effective radiation dose of
2.60 mSv. The resulting total effective radiation dose from the CT scan and FDG
will be 4.00 mSv in healthy controls and 8.00 mSv in patients (2 18F-FDG
PET-CT-scans). The effective dose is between 1-10 mSv and therefore comes
within category IIb according to the risk categorization based on ICRP-62
(following the LUMC complex license of May 20th 2010, paragraph VIII), which
involves a risk for the irradiated individual in the order of one in ten
thousand, which is considered low and does not present any danger to the
environment as recently described. Furthermore, the above described 18F-FDG
PET-CT-scan protocol is a standard procedure performed at the University of
Maastricht and the LUMC in research with (young) healthy volunteers. In
accordance with this low risk category, our research findings may have the
potential to
exert important beneficial effects concerning future therapeutic strategies
targeting the obesity epidemic.
An allergic reaction to 18F-FDG is extremely rare and usually mild. We will
monitor the subject during the study day to see if any allergic symptoms occur,
such as shortness of breath, skin reactions or nausea.
Subjects with contraindications for MRI will be excluded. There are no known
risks known associated with the use of MRI.
It is important to state that the risks of sodium oxybate are not added risks
to this study, since sodium oxybate treatment is not influenced by this study.