Metabolic differences between narcoleptic patients and healthy controls, and the effect of sodium oxybate in patients

Narcolepsy is a debilitating sleep disorder, with an estimated prevalence of
5-6 per 10,000 in the Western population.1,2 It primarily affects the
organization and regulation of sleep and wakefulness. The main symptoms are
excessive daytime sleepiness, cataplexy (a sudden muscle weakness triggered by
emotions), and fragmented nocturnal sleep. Less explored symptoms include
impaired vigilance and memory impairments.

In 1999, deficiencies in hypocretin neurotransmission were shown to be the
fundamental cause of narcolepsy. Animal data showed that the hypocretin system
is not only involved in sleep regulation, but also in the regulation of various
hormonal ensembles and (sympathetic) autonomic nervous system functions.3,4

These findings prompted additionial research into additional symptoms in human
narcolepsy. Indeed, obesity and hormonal alterations have now been identified
as important and prevalent features of the disease.5-9 Why narcoleptic patients
grow obese is not known. The occurrence of daytime sleep is not a sufficient
explanation, and 24-hour caloric intake in narcoleptics seems to be even lower
compared to healthy controls.10 At this point, the most likely explanation is
a decreased sympathetic tone with a resulting decrease in energy expenditure.
However, this has not been proven yet

1. To compare energy expenditure in detail between narcolepsy patients and
healthy
controls.

2. To compare insulin sensitivity between patients with narcolepsy and healthy
controls.

3. To establish the impact of chronic sodium oxybate treatment (3-4 months) on
these
metabolic features in hypocretin-deficient narcoleptic patients.

Total and resting energy expenditure, fuel oxidation and insulin sensitivity
will be measured in all subjects at baseline by respiration chamber, indirect
calorimetry, doubly-labeled water and hyperinsulinemic euglycemic clamp,
respectively.
After these measurements, the narcoleptic patients will be treated with sodium
oxybate for 3 months by their own neurologist. If this treatment is succesfull,
all parameters will be assessed again in these patients.
In the healthy controls only the parameters on energy expenditure will be
repeatedly assessed to take into account the seasonal influence. This will be
done three months after the first assessment.

Participation takes time and some discomfort. Introduction of the iv's may hurt
a bit and give a haematoma.
Isotopes are stable non-radioactive, and also non-toxic in the doses used.

During the hyperinsulinemic euglycemic clamp procedure serum glucose levels
will be determined every 5 minutes and, if necessary, the glucose infusion rate
will be adapted so the chance of hypoglycemia is very low. The isotopes used
during the clamp procedure are non- radioactive and no side effects will be
expected.

During the admissions at the hospital there will be a restriction of movement
freedom. The only problem that may be expected is in case of claustrophobia.
Subjects with claustrophobia won't be included so no problem will be expected.

Narcolepstic patients who have to stop sodium oxybate can experience a slow
return of their complaints. This will be evaluated by their own physician.

Participants will receive ¤375,- (healthy controls ¤300,-)