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Narcolepsy Protect Against Alzheimer's Disease? (PROTECMAN)

Primary Purpose

Narcolepsy, Amyloid Pathology

Status

Completed

Phase

Not Applicable

Locations

France

Study Type

Interventional

Intervention

PET-scan18F-AV-45

About this trial

This is an interventional other trial for Narcolepsy focused on measuring Narcolepsy, Alzheimer, Orexin, Amyloid, PET-amyloid imaging

Eligibility Criteria

65 Years - 85 Years (Older Adult)All SexesDoes not accept healthy volunteers

Inclusion criteria:

Narcolepsy group:

Patients with narcolepsy type 1 older than 65 y.o. with orexin deficiency as required by international diagnosis criteria (ICSD3) with a follow-up in the national reference center for narcolepsy;
Treated or not with psychostimulant drugs in relation to disease symptoms;
Patients with CSF samples available or with scheduled lumbar puncture for diagnosis purpose;
No contra-indications of the PET-scan18F-AV-45
With a free and informed consent to participate to the study.

Control group:

Subjects already included in the MEMENTO-AMYging and/or MAPT-AV45 ancillary studies in the memory center with normal cognitive tests after neuropsychological assessments especially in the episodic memory tests and the brain amyloid PET-scan18F-AV-45 data with SuVr measurements.

Exclusion criteria:

Controls subjects or patients without free and informed consent to participate to the study
No PET-scan18F-AV-45 data available
No CSF samples
Pathologies being life-threatening in a short term
Patients deprived of freedom by court or administrative order
Patients living in institution
Major protected by the Law.

Sites / Locations

Montpellier University Hospital, Gui de Chauliac

Arms of the Study

Arm 1

Arm 2

Arm Type

Other

Arm Label

NarCo

CoS

Arm Description

Narcolepsy type 1 over 65 years old

Cognitevement healthy controls

Outcomes

Primary Outcome Measures

Mean of cortical SuVr based of the PET-scan18F-AV-45 imaging

Secondary Outcome Measures

Mean regional SuVr with PET-scan AV45

CSF Amyloid Aβ42

pg/ml

CSF Amyloid Aβ40

pg/ml

CSF Tau protein

pg/ml

CSF Orexin concentration

pg/ml

Night-time sleep duration

Hours/night

Day-time sleep duration

Hours/day

Cataplexy

Numbers/week

Epworth sleepiness scale (ESS)

Score as a number

Beck Depression Inventory (BDI)

Score as a number

European Quality of Life Dimension (EQL-5)

Score as a number

Full Information

NCT ID

NCT03378453

First Posted

August 2, 2016

Last Updated

December 18, 2017

Sponsor

University Hospital, Montpellier

1. Study Identification

Unique Protocol Identification Number

NCT03378453

Brief Title

Narcolepsy Protect Against Alzheimer's Disease?

Acronym

PROTECMAN

Official Title

Narcolepsy Protect Against Alzheimer's Disease? Protective Role of Low Rates of Orexin on the Occurrence of Intracerebral Amyloid Deposits Characteristic of the Alzheimer's Disease: A Pilot Study

Study Type

Interventional

2. Study Status

Record Verification Date

December 2017

Overall Recruitment Status

Completed

Study Start Date

April 7, 2016 (Actual)

Primary Completion Date

November 2017 (Actual)

Study Completion Date

November 2017 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

University Hospital, Montpellier

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

Links between orexin and amyloid processes have been underlined recently. During the Alzheimer's process an upregulation of the orexin mechanism has been observed. The pathophysiological mechanism of narcolepsy type 1 is linked to orexin deficiency. Thus, the investigators hypothesized that patients with narcolepsy may be protected from amyloid brain lesions, hallmarks of the Alzheimer's process. To test this hypothesis, the investigators analyzed the brain amyloid load measured by PET-scan amyloid brain imaging in patients with narcolepsy type 1 compared to controls without cognitive deficits.

Detailed Description

The lack of innovative treatments in Alzheimer' disease (AD) is due to the non-understanding of the pathological process. The investigators need to include the latest concept of the sleep-wake/circadian kinetics of proteins in the brain, the new theory of the wash-out of pathological proteins via the brain glymphatic system during sleep and act at an early stage. New pathways are opened to better understand proteinopathies' processes and to propose new therapeutics interventions. The variations of the production/clearance curves of amyloid in the cerebrospinal fluid (CSF) during circadian rhythms and sleep-wake cycles have been demonstrated in in vivo metabolism experimentations. Suprachiasmatic nucleus damages due to AD may induce circadian regulation dysfunction and secondary sleep/wake cycle alterations. Key sleep/wake cycle neuromediators (Orexin-A, melatonin) are involved in the regulation of brain amyloid levels. The influence of orexin-A signaling on Aβ metabolism in animals and humans was recently highlighted. In rats, orexin-A release shows a 24-h fluctuation similar to that of brain interstitial fluid Aβ. In transgenic mice that overexpress amyloid precursor protein (APP), brain interstitial fluid Aβ concentration increases during wakefulness and after orexin-A infusion. Conversely, it decreases during sleep and after infusion of an orexin-A receptor antagonist6. In transgenic mice that overexpress APP/presenilin1 (PS1), in which the orexin gene is knocked out, a reduction of Aβ pathology was found, possibly caused by changes in sleep time. Orexin-A is linked to Aβ42 in AD and an increase of CSF orexin-A is observed in AD vs. controls, possibly related to sleep deterioration and neurodegeneration. The narcolepy with cataplexy type 1 is the only disease with a specific orexin deficiency. Montpellier team have previously underlined in 15 patients with narcolepsy type 1 a normal level of Aβ42 in the CSF. The clinical expertise of the narcolepsy center suggested that the frequency of AD in old narcoleptic patients is low. The hypothesis was that patients with narcolepsy type 1 may be protected from amyloid brain lesions, hallmarks of the Alzheimer's process. The objective was to determine whether the brain amyloid load by PET-scan18 F-AV-45 measured with a semi-quantitative analysis (mean cortical SuVr) is lower in patients with narcolepsy type 1 older than 65 years-old than in cognitively normal age- and gender-matched controls.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Narcolepsy, Amyloid Pathology

Keywords

Narcolepsy, Alzheimer, Orexin, Amyloid, PET-amyloid imaging

7. Study Design

Primary Purpose

Other

Study Phase

Not Applicable

Interventional Study Model

Parallel Assignment

Masking

Outcomes Assessor

Allocation

Non-Randomized

Enrollment

38 (Actual)

8. Arms, Groups, and Interventions

Arm Title

NarCo

Arm Type

Other

Arm Description

Narcolepsy type 1 over 65 years old

Arm Title

CoS

Arm Type

Other

Arm Description

Cognitevement healthy controls

Intervention Type

Device

Intervention Name(s)

PET-scan18F-AV-45

Intervention Description

The PET-scan18F-AV-45 is a PET-scan dedicated to analyze the amyloid load in the brain with the AV45 tracer by the measurement of the mean cortical SuVr

Intervention Type

Device

Intervention Name(s)

PET-scan18F-AV-45

Intervention Description

PET-scan18F-AV-45 already done in another protocol MEMENTO-AMYging

Primary Outcome Measure Information:

Title

Mean of cortical SuVr based of the PET-scan18F-AV-45 imaging

Description

Mean of cortical SuVr based of the PET-scan18F-AV-45 imaging

Time Frame