NCT03754348

Brief 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.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
78

participants targeted

Target at P50-P75 for not_applicable

Timeline
Completed

Started Jan 2019

Typical duration for not_applicable

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

November 5, 2018

Completed
22 days until next milestone

First Posted

Study publicly available on registry

November 27, 2018

Completed
2 months until next milestone

Study Start

First participant enrolled

January 15, 2019

Completed
2.8 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

November 18, 2021

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

November 18, 2021

Completed
Last Updated

May 29, 2024

Status Verified

March 1, 2022

Enrollment Period

2.8 years

First QC Date

November 5, 2018

Last Update Submit

May 27, 2024

Conditions

Keywords

narcolepsy type 1orexinhypocretin[18F] DPA-714biomarkerauto immunitykleine-levin syndrome

Outcome Measures

Primary Outcomes (1)

  • Quantification of microglial activation in the hypothalamus (SuVr) of adult NT1 patients compared to controls

    1 day

Secondary Outcomes (5)

  • Correlation between microglial activation in the hypothalamus, thalamus, and other regions of interest in adult and child patients and severity of the disease

    1 day

  • Correlation between microglial activation in the hypothalamus, thalamus, and other regions of interest in adult and child patients and electrophysiological biomarkers

    1 day

  • Correlation between microglial activation in the hypothalamus, thalamus, and other regions of interest in adult and child patients and inflammatory biomarkers

    1 day

  • Microglial activation in the hypothalamus, thalamus, and other regions of interest in KLS patients vs NT1 patients

    1 day

  • Correlation between microglial activation in the hypothalamus, thalamus, and other regions of interest in KLS patients and time and severity of the disease (clinical, polysomnographic and biologic parameters)

    1 day

Study Arms (3)

NT1 group

EXPERIMENTAL

hypothalamus neuroinflammation evaluation in Narcoleptic patients

Radiation: PET scan with tracer injection [18F] DPA-714

Control group

OTHER

hypothalamus neuroinflammation evaluation in control patients (patients without hypersomnia or inflammatory pathology)

Radiation: PET scan with tracer injection [18F] DPA-714

KLS group

EXPERIMENTAL

hypothalamus neuroinflammation evaluation in Kleine-Levin syndrome patients

Radiation: PET scan with tracer injection [18F] DPA-714

Interventions

the subject will receive a dose of 3.5MBq / kg intravenous (in bolus) more or less 20%, knowing that the minimum dose injected is unchanged at 150MBq and the maximum dose at 370 MBq. Irradiation will remain below 10 mSv

Control groupKLS groupNT1 group

Eligibility Criteria

Age10 Years+
Sexall
Healthy VolunteersNo
Age GroupsChild (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

  • For all groups :
  • Written agreement for participation
  • Able to understand instructions and information data
  • Without any immunomodulatory, immunosuppressant, or anti-inflamatory medication
  • For NT1 patients:
  • years-old or more
  • Responding to NT1 criteria (ICSD-3)
  • Under psychostimulant or not for narcolepsy
  • For KLS patients:
  • years-old or more
  • KLS diagnosis
  • For controls
  • years-old or more
  • Absence of narcolepsy
  • Absence of acute or chronic inflammatory disease

You may not qualify if:

  • People without public insurance regime
  • Specific contraindication to the use of PET (specific allergy related to the ligand).
  • Pregnant and breastfeeding women
  • Persons deprived of liberty by judicial or administrative decision
  • People hospitalized without consent, or subject to legal protection
  • Persons unable to consent

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

University Hospital of Montpellier

Montpellier, France

Location

Related Publications (1)

  • Barateau L, Krache A, Da Costa A, Lecendreux M, Debs R, Chenini S, Arlicot N, Vourc'h P, Evangelista E, Alonso M, Salabert AS, Silva S, Beziat S, Jaussent I, Mariano-Goulart D, Payoux P, Dauvilliers Y. Microglia Density and Its Association With Disease Duration, Severity, and Orexin Levels in Patients With Narcolepsy Type 1. Neurology. 2024 May;102(10):e209326. doi: 10.1212/WNL.0000000000209326. Epub 2024 Apr 26.

MeSH Terms

Conditions

Narcolepsy 1Kleine-Levin Syndrome

Interventions

Magnetic Resonance SpectroscopyProduct LabelingN,N-diethyl-2-(2-(4-(2-fluoroethoxy)phenyl)-5,7-dimethylpyrazolo(1,5-a)pyrimidin-3-yl)acetamide

Condition Hierarchy (Ancestors)

Disorders of Excessive SomnolenceSleep Disorders, IntrinsicDyssomniasSleep Wake DisordersNervous System DiseasesMental Disorders

Intervention Hierarchy (Ancestors)

Spectrum AnalysisChemistry Techniques, AnalyticalInvestigative TechniquesProduct PackagingIndustryTechnology, Industry, and Agriculture

Study Design

Study Type
interventional
Phase
not applicable
Allocation
NON RANDOMIZED
Masking
SINGLE
Who Masked
OUTCOMES ASSESSOR
Purpose
BASIC SCIENCE
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

November 5, 2018

First Posted

November 27, 2018

Study Start

January 15, 2019

Primary Completion

November 18, 2021

Study Completion

November 18, 2021

Last Updated

May 29, 2024

Record last verified: 2022-03

Locations