Primary objective:1. To assess the effect of 4 weeks SXB treatment on basal and cold-induced WAT lipolysis (assessed by levels of circulating free fatty acids) in narcolepsy type 1 patients. Secondary objectives:1. To assess the effects of 4 weeks…
ID
Source
Brief title
Condition
- Other condition
- Hypothalamus and pituitary gland disorders
- Lipid metabolism disorders
Synonym
Health condition
hypersomnieën
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The effect of 4 weeks SXB treatment on basal and cold-induced levels of
circulating free fatty acids (FFA) in narcolepsy type 1 patients.
Secondary outcome
1. Baseline differences between narcolepsy type 1 patients and matched controls
in:
- Indirect markers for basal and cold-induced WAT lipolysis (measured by
expression of genes and (phosphorylated) proteins involved in lipolysis and
lipid content).
- Serum markers for lipid metabolism metabolism (triglycerides (TG), total
cholesterol (TC), high density lipoprotein cholesterol (HDL-C), low density
lipoprotein cholesterol (LDL-C), free fatty acids (FFA)).
- Thermoneutral and cold-induced changes in free fatty acids (FFA).
- Serum markers for glucose metabolism (glucose, insulin, cortisol).
- Resting energy expenditure: measured by indirect calorimetry.
- Skin temperature (as a proxy of BAT activity): measured by infrared
thermography.
- Fat/lean mass: measured by body composition analyzer (InBody720).
- mRNA immune gene expression: measured by microfluidic qPCR analyses on whole
blood.
- Fecal microbiota composition: measured by 16S sequencing.
2. The effect of 4 weeks of SXB treatment in narcolepsy type 1 patients on all
above-mentioned outcomes, excluding free fatty acids (FFA) which is already the
primary outcome measure.
Background summary
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), the current therapy for the disease. A mean loss of 5.2
kg in three months has been reported in several studies (1-3). This effect
appears to be more pronounced in women compared to men [3]. The available
animal studies and one human study show an increase in sympathetic activity
after SXB administration (4). In line with this, SXB treatment increases
lipolysis in narcolepsy type 1 patients (1). Furthermore, our recent
experiments in mice suggest a role for remodeling of white adipose tissue (WAT)
and changes in the microbiome in the weight-losing effects of SXB. However,
thus far the underlying mechanism and involved metabolic tissues mediating the
weight loss in narcolepsy type 1 patients after initiation of SXB treatment
remain unclear. Therefore, we aim to investigate the short-term effects of SXB
treatment on metabolic tissues that importantly contribute to lipid metabolism,
e.g. WAT and brown adipose tissue (BAT) as well as the microbiome in patients
with narcolepsy type 1. Because the weight losing effects of SXB is more
pronounced in women compared to men, only females will be investigated in this
study.
Study objective
Primary objective:
1. To assess the effect of 4 weeks SXB treatment on basal and cold-induced WAT
lipolysis (assessed by levels of circulating free fatty acids) in narcolepsy
type 1 patients.
Secondary objectives:
1. To assess the effects of 4 weeks SXB treatment on indirect markers of basal
and cold-induced WAT lipolysis (by the expression of genes and (phosphorylated)
proteins involved in lipolysis, and lipid content) in narcolepsy type 1
patients.
2. To assess differences in gene and protein expression, and lipid content in
subcutaneous WAT between narcolepsy type 1 patients and matched controls.
3. To assess the effect of 4 weeks SXB treatment on cold-induced lipoprotein
dynamics in blood, and supraclavicular skin temperature (as a proxy of BAT
activity) in narcolepsy type 1 patients.
4. To assess differences in cold-induced lipoprotein dynamics in blood, and
supraclavicular skin temperature (as a proxy of BAT activity) between
narcolepsy type 1 patients and matched controls.
5. To assess effects of 4 weeks SXB treatment on fecal microbiota composition
and resting energy expenditure in narcolepsy type 1 patients.
6. To assess differences in fecal microbiota composition and resting energy
expenditure between narcolepsy type 1 patients and matched controls.
Study design
Prospective observational study.
Study burden and risks
The subcutaneous WAT biopsy may cause pain and often causes bruising, which
will disappear within several days. The feeling of fainting may occur during or
shortly after the WAT biopsy and/or blood sampling. If so, the subject will be
instructed to lie down immediately. The WAT biopsy scheduled after 21 days
(only for patient group) will be performed on the other side of the abdomen
compared to day 1. It is important to state that the risks of SXB are not added
risks to this study, since subjects will be started on SXB treatment
independent of this study.
Albinusdreef 2
Leiden 2333ZA
NL
Albinusdreef 2
Leiden 2333ZA
NL
Listed location countries
Age
Inclusion criteria
Patients:
1. Narcolepsy type 1 based on ICSD-3 criteria.
2. >=18 and <40 years of age.
3. Biologically female.
4. White Caucasian descent.
5. Clinical indication for SXB treatment.
6. BMI >= 25 kg/m2
Matched controls:
1. Biologically female.
2. Age- and BMI-match with patient.
3. White Caucasian descent.
Exclusion criteria
Patients and matched controls:
1. Previous use of SXB.
2. Contraindications for SXB treatment.
3. Sleep-wake disorders other than narcolepsy type 1.
4. Renal, hepatic or endocrine disease.
5. Use of medication known to influence glucose and/or lipid metabolism or
brown adipose tissue activity (e.g. β-adrenergic receptor blockers).
6. Participation in an intensive weight-loss program or vigorous exercise
program during the year before the start of the study.
7. Pregnant during the study days (due to unreliable body composition
measurements on the InBody machine)
Design
Recruitment
metc-ldd@lumc.nl
metc-ldd@lumc.nl
metc-ldd@lumc.nl
metc-ldd@lumc.nl
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In other registers
| Register | ID |
|---|---|
| CCMO | NL74154.058.20 |