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Narcolepsy Protect Against Alzheimer's Disease? (PROTECMAN)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03378453
Recruitment Status : Completed
First Posted : December 19, 2017
Last Update Posted : December 19, 2017
Sponsor:
Information provided by (Responsible Party):
University Hospital, Montpellier

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.

Condition or disease Intervention/treatment Phase
Narcolepsy Amyloid Pathology Device: PET-scan18F-AV-45 Not Applicable

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 38 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: Single (Outcomes Assessor)
Primary Purpose: Other
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
Actual Study Start Date : April 7, 2016
Actual Primary Completion Date : November 2017
Actual Study Completion Date : November 2017


Arm Intervention/treatment
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

CoS
Cognitevement healthy controls
Device: PET-scan18F-AV-45
PET-scan18F-AV-45 already done in another protocol MEMENTO-AMYging




Primary Outcome Measures :
  1. 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


Secondary Outcome Measures :
  1. Mean regional SuVr with PET-scan AV45 [ Time Frame: Upon study completion, an average of one year ]
  2. CSF Amyloid Aβ42 [ Time Frame: Upon study completion, an average of one year ]
    pg/ml

  3. CSF Amyloid Aβ40 [ Time Frame: Upon study completion, an average of one year ]
    pg/ml

  4. CSF Tau protein [ Time Frame: Upon study completion, an average of one year ]
    pg/ml

  5. CSF Orexin concentration [ Time Frame: Upon study completion, an average of one year ]
    pg/ml

  6. Night-time sleep duration [ Time Frame: Upon study completion, an average of one year ]
    Hours/night

  7. Day-time sleep duration [ Time Frame: Upon study completion, an average of one year ]
    Hours/day

  8. Cataplexy [ Time Frame: Upon study completion, an average of one year ]
    Numbers/week

  9. Epworth sleepiness scale (ESS) [ Time Frame: Upon study completion, an average of one year ]
    Score as a number

  10. Beck Depression Inventory (BDI) [ Time Frame: Upon study completion, an average of one year ]
    Score as a number

  11. European Quality of Life Dimension (EQL-5) [ Time Frame: Upon study completion, an average of one year ]
    Score as a number



Information from the National Library of Medicine

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Ages Eligible for Study:   65 Years to 85 Years   (Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03378453


Locations
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France
Montpellier University Hospital, Gui de Chauliac
Montpellier, France, 34295
Sponsors and Collaborators
University Hospital, Montpellier
Investigators
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Study Chair: Audrey Gabelle, MD, PhD Montpellier University Hospital
Publications:

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: University Hospital, Montpellier
ClinicalTrials.gov Identifier: NCT03378453    
Other Study ID Numbers: 9636
First Posted: December 19, 2017    Key Record Dates
Last Update Posted: December 19, 2017
Last Verified: December 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided
Keywords provided by University Hospital, Montpellier:
Narcolepsy
Alzheimer
Orexin
Amyloid
PET-amyloid imaging
Additional relevant MeSH terms:
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Alzheimer Disease
Narcolepsy
Amyloidosis
Dementia
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Tauopathies
Neurodegenerative Diseases
Neurocognitive Disorders
Mental Disorders
Proteostasis Deficiencies
Metabolic Diseases
Disorders of Excessive Somnolence
Sleep Disorders, Intrinsic
Dyssomnias
Sleep Wake Disorders