Microglial Activation in Narcolepsy Type 1 and Kleine-Levin Syndrome: Positron Emission Tomography (PET) Study in [18F] DPA-714 (NARCOGLIE)

May 27, 2024 updated by: University Hospital, Montpellier
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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed 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.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
78

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Contact Backup

Study Locations

  • France
      • Montpellier, France
        • University Hospital of Montpellier

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

6 years and older (Child, Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion criteria:

  1. For all groups :

    • Written agreement for participation
    • Able to understand instructions and information data
    • Without any immunomodulatory, immunosuppressant, or anti-inflamatory medication

  2. For NT1 patients:

    • 10 years-old or more
    • Responding to NT1 criteria (ICSD-3)
    • Under psychostimulant or not for narcolepsy

  3. For KLS patients:

    • 10 years-old or more
    • KLS diagnosis

  4. For controls

    • 18 years-old or more
    • Absence of narcolepsy
    • Absence of acute or chronic inflammatory disease

Exclusion criteria (for all groups):

  • 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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Basic Science
  • Allocation: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Single

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: NT1 group
hypothalamus neuroinflammation evaluation in Narcoleptic patients
Radiation: PET scan with tracer injection [18F] DPA-714
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
Other: Control group
hypothalamus neuroinflammation evaluation in control patients (patients without hypersomnia or inflammatory pathology)
Radiation: PET scan with tracer injection [18F] DPA-714
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
Experimental: KLS group
hypothalamus neuroinflammation evaluation in Kleine-Levin syndrome patients
Radiation: PET scan with tracer injection [18F] DPA-714
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

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Time Frame
Quantification of microglial activation in the hypothalamus (SuVr) of adult NT1 patients compared to controls
Time Frame: 1 day
1 day

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Time Frame
Correlation between microglial activation in the hypothalamus, thalamus, and other regions of interest in adult and child patients and severity of the disease
Time Frame: 1 day
1 day
Correlation between microglial activation in the hypothalamus, thalamus, and other regions of interest in adult and child patients and electrophysiological biomarkers
Time Frame: 1 day
1 day
Correlation between microglial activation in the hypothalamus, thalamus, and other regions of interest in adult and child patients and inflammatory biomarkers
Time Frame: 1 day
1 day
Microglial activation in the hypothalamus, thalamus, and other regions of interest in KLS patients vs NT1 patients
Time Frame: 1 day
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)
Time Frame: 1 day
1 day

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
University Hospital, Montpellier

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Centre Hospitalier Universitaire de Nīmes

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
January 15, 2019

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
November 18, 2021

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
November 18, 2021

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
November 5, 2018

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
November 22, 2018

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
November 27, 2018

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
May 29, 2024

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
May 27, 2024

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
March 1, 2022

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • RECHMPL18_0067

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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