Clinical Trial Details
— Status: Completed
Administrative data
| NCT number |
NCT03754348 |
| Other study ID # |
RECHMPL18_0067 |
| Secondary ID |
|
| Status |
Completed |
| Phase |
N/A
|
| First received |
|
| Last updated |
|
| Start date |
January 15, 2019 |
| Est. completion date |
November 18, 2021 |
Study information
| Verified date |
March 2022 |
| Source |
University Hospital, Montpellier |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial Summary
Type 1 narcolepsy (NT1) is a chronic sleep disorder caused by the selective and irreversible
loss of neurons from the hypothalamus, which synthesizes a neurotransmitter: hypocretin
(Hcrt) / orexin. The exact cause of this destruction is still unknown, but the autoimmune
hypothesis is strongly favored, involving the interaction of genetic and environmental
factors. The treatment of NT1 is currently only symptomatic, targeting hypersomnolence and
cataplexy. To prevent the destruction of Hcrt neurons, immunomodulatory agents have been
tested, with varying efficacy, probably due to varying degrees of hypothalamic impairment and
stages of disease progression. During microglial activation, a condition associated with
neuroinflammation in the brain, there is an increase in the mitochondrial translocation
protein (TSPO), which can be quantified in vivo by specific tracers, such as the [18F] DPA-
714, in positron emission tomography (PET), a very sensitive nuclear imaging technique. The
aim here is to study microglial activation in PET [18F] DPA-714 in NT1 patients with recent
evolution in comparison with controls; then analyze the effect of age, and the severity of
symptoms on this PET imaging biomarker. The hypothesis is that microglial activation,
especially of the hypothalamic region, is greater in NT1 than controls.
Description:
Formerly known as narcolepsy with cataplexy, narcolepsy type 1 (NT1) is a rare and disabling
sleep pathology that affects 0.02% of the population. It occurs mainly in young adults and
children, with repercussions throughout their existence. It is characterized by excessive
daytime sleepiness (EDS), which is often the most disabling symptom. Diurnal sleep access is
irrepressible, typically short-lived, and refreshing. Cataplexies are the most specific,
almost pathognomonic sign of this condition. It is a loss of muscle tone in full
consciousness, sudden, triggered by an often positive emotion (laugh, excitement, joke).
Nighttime sleep is also disturbed and there may be other signs of paradoxical sleep
dysregulation such as hypnagogic hallucinations (at sleep) or hypnopompic (waking)
hallucinations, and sleep paralysis.
The diagnosis is confirmed by a polysomnographic recording (PSG) followed by iterative sleep
latency tests (TILE) the next day. According to the new international criteria (ICSD-3),
patients have a sleep latency of less than or equal to 8 minutes to TILE, and at least 2
sleep in paradoxical sleep (ESP) . An ESP during the previous night PSG can replace a TILE
ESP. Typical cataplexies must also be found during the interrogation, but a level of
hypocretin-1 collapsed in cerebrospinal fluid (CSF) (<110 ng / L) can now be sufficient for
diagnosis, given its very high specificity ( 99%) and sensitivity (> 87%) for NT1.
NT1 is due to the selective and irreversible loss of Hcrt neurons. The exact cause of this
destruction is still unknown, but the autoimmune hypothesis is strongly favored. The etiology
is probably multifactorial, involving genetic and environmental factors. In fact, 97% of
patients with NT1 are carriers of the HLA (Human Leukocyte Antigen) allele DQB1 * 06: 02, a
class II major histocompatibility complex (MHC) allele.
Treatments of NT1 are currently only symptomatic, targeting the different symptoms:
drowsiness, poor sleep at night, cataplexy, and other symptoms related to dysregulation of
sleep Microglial activation is involved in the neuroinflammation process of certain central
nervous system pathologies.
When microglia are activated, following aggression or cellular inflammation, the expression
of TSPO increases. Positron Emission Tomography (PET) is a nuclear imaging technique that can
be used to create anatomical and molecular images with high sensitivity. New TSPO-specific
tracers have been recently developed, such as [18F] DPA-714, to quantify in vivo microglial
activation in brain PET.
The goal here is to study the cerebral microglial activation in PET in NT1 patients with
recent evolution (appearance of the first symptoms - somnolence and cataplexy - less than 2
years ago) in comparison with controls; then analyze the effect of age, and the severity of
symptoms on this PET imaging biomarker. Thus, we hypothesize microglial activation,
particularly of the hypothalamic region, in NT1 patients at an early stage of disease
progression, possibly correlated with the severity of symptoms. To test this hypothesis, we
will compare the in vivo microglial activation with PET [18F] DPA-714 in NT1 subjects, versus
control subjects followed for another age-and-sex-matched non-narcolepsy and hypersomnia-free
sleep pathology. The images will be analyzed semi-quantitatively by determining SuVr (or
normalized binding value), a method validated in international studies.
