Narcolepsy Protect Against Alzheimer's Disease? (PROTECMAN)

December 18, 2017 updated by: University Hospital, Montpellier

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

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

38

Phase

  • 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 Locations

  • France
      • Montpellier, France, 34295
        • Montpellier University Hospital, Gui de Chauliac

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

Ages Eligible for Study

63 years to 83 years (Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

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: Other
  • Allocation: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Single

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Other: NarCo
Narcolepsy type 1 over 65 years old
Device: PET-scan18F-AV-45
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
Device: PET-scan18F-AV-45
PET-scan18F-AV-45 already done in another protocol MEMENTO-AMYging
Other: CoS
Cognitevement healthy controls
Device: PET-scan18F-AV-45
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
Device: PET-scan18F-AV-45
PET-scan18F-AV-45 already done in another protocol MEMENTO-AMYging

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Mean of cortical SuVr based of the PET-scan18F-AV-45 imaging
Time Frame: Upon study completion, an average of one year
Mean of cortical SuVr based of the PET-scan18F-AV-45 imaging
Upon study completion, an average of one year

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Mean regional SuVr with PET-scan AV45
Time Frame: Upon study completion, an average of one year
Upon study completion, an average of one year
CSF Amyloid Aβ42
Time Frame: Upon study completion, an average of one year
pg/ml
Upon study completion, an average of one year
CSF Amyloid Aβ40
Time Frame: Upon study completion, an average of one year
pg/ml
Upon study completion, an average of one year
CSF Tau protein
Time Frame: Upon study completion, an average of one year
pg/ml
Upon study completion, an average of one year
CSF Orexin concentration
Time Frame: Upon study completion, an average of one year
pg/ml
Upon study completion, an average of one year
Night-time sleep duration
Time Frame: Upon study completion, an average of one year
Hours/night
Upon study completion, an average of one year
Day-time sleep duration
Time Frame: Upon study completion, an average of one year
Hours/day
Upon study completion, an average of one year
Cataplexy
Time Frame: Upon study completion, an average of one year
Numbers/week
Upon study completion, an average of one year
Epworth sleepiness scale (ESS)
Time Frame: Upon study completion, an average of one year
Score as a number
Upon study completion, an average of one year
Beck Depression Inventory (BDI)
Time Frame: Upon study completion, an average of one year
Score as a number
Upon study completion, an average of one year
European Quality of Life Dimension (EQL-5)
Time Frame: Upon study completion, an average of one year
Score as a number
Upon study completion, an average of one year

Collaborators and Investigators

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

Sponsor

University Hospital, Montpellier

Investigators

  • Study Chair: Audrey Gabelle, MD, PhD, Montpellier University Hospital

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

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)

April 7, 2016

Primary Completion (Actual)

November 1, 2017

Study Completion (Actual)

November 1, 2017

Study Registration Dates

First Submitted

August 2, 2016

First Submitted That Met QC Criteria

December 18, 2017

First Posted (Actual)

December 19, 2017

Study Record Updates

Last Update Posted (Actual)

December 19, 2017

Last Update Submitted That Met QC Criteria

December 18, 2017

Last Verified

December 1, 2017

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 9636

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

Undecided

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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