ALZ-OREX: Biomarkers of Sleep-wake Cycle in Prodromal Alzheimer's Disease: Role in Cognitive Decline?

Sponsor

University Hospital, Montpellier (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT05629871

Collaborator

Institut National de la Santé Et de la Recherche Médicale, France (Other)

132

Enrollment

Locations

Arm

50.6

Anticipated Duration (Months)

Patients Per Site

0.9

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Alzheimer's disease (AD) is characterised by a progressive loss of memory and cognitive function. In the early stages of AD, there is a progressive accumulation of molecules: β-amyloid peptides (Aβ) in the brain. There is a link between the accumulation of Aβ peptides and the deterioration of sleep, but current knowledge does not confirmed this link. The objective of this study is to define whether there is a link between cognitive decline and sleep disorders. If a correlation is found, this could allow earlier treatment of sleep disorders in the longer term in order to slow the development of AD.

Condition or Disease	Intervention/Treatment	Phase
Neuropathology	Procedure: Polysomnography Behavioral: Neuropsychological assessment Behavioral: Questionnaires on sleep and behavioural problems Procedure: Actimetry Diagnostic Test: Fractional diuresis Procedure: Internal temperature measurement Other: Biomarker assay	N/A

Study Design

Study Type:

Interventional

Anticipated Enrollment :

132 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Diagnostic

Official Title:

Biomarkers of Sleep-wake Cycle in Prodromal Alzheimer's Disease: Role in Cognitive Decline?

Anticipated Study Start Date :

Mar 15, 2023

Anticipated Primary Completion Date :

Jun 1, 2027

Anticipated Study Completion Date :

Jun 1, 2027

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Single arm Alzheimer	Procedure: Polysomnography Polysomnography will be performed for 24 hours at inclusion and 24 months Behavioral: Neuropsychological assessment A full neuropsychological assessment will be performed at inclusion, 12 and 24 months Behavioral: Questionnaires on sleep and behavioural problems Questionnaires on sleep and behavioural problems Procedure: Actimetry Measurement of actimetrics for 14 days at inclusion and at 24 months Diagnostic Test: Fractional diuresis Split diuresis from 7pm-7am, 7am-12am and 12pm-19pm during polysomnography at inclusion inclusion and 24 months to measure melatonin concentration Procedure: Internal temperature measurement eCelsius capsule to measure internal temperature at inclusion and 24 months Other: Biomarker assay Determination of the biomarkers Aβ42, Aβ40, Tau and P-Tau in blood and in the cerebrospinal fluid

Arm

Intervention/Treatment

Experimental: Single arm

Alzheimer

Procedure: Polysomnography

Polysomnography will be performed for 24 hours at inclusion and 24 months

Behavioral: Neuropsychological assessment

A full neuropsychological assessment will be performed at inclusion, 12 and 24 months

Behavioral: Questionnaires on sleep and behavioural problems

Questionnaires on sleep and behavioural problems

Procedure: Actimetry

Measurement of actimetrics for 14 days at inclusion and at 24 months

Diagnostic Test: Fractional diuresis

Split diuresis from 7pm-7am, 7am-12am and 12pm-19pm during polysomnography at inclusion inclusion and 24 months to measure melatonin concentration

Procedure: Internal temperature measurement

eCelsius capsule to measure internal temperature at inclusion and 24 months

Other: Biomarker assay

Determination of the biomarkers Aβ42, Aβ40, Tau and P-Tau in blood and in the cerebrospinal fluid

Outcome Measures

Primary Outcome Measures

Change in the Free and Cued Selective Reminding Test (FCSRT) scale score [From inclusion to 24 months]
The FCSRT test evaluates memory, the score obtained is between 0 and 48, higher score mean a better outcome

Secondary Outcome Measures

Change in the Free and Cued Selective Reminding Test (FCSRT) scale score [From inclusion to 12 months]
The FCSRT test evaluates memory, the score obtained is between 0 and 48, higher score mean a better outcome
Cognitive decline in ADCS-PACC composite score [At inclusion and at 24 months]
The ADCS-PACC composite score is used to assess cognitive decline
Cognitive decline in the Alzheimer's Disease Cooperative Study- Preclinical Alzheimer Cognitive Composite (ADCS-PACC) composite score [At inclusion and at 12 months]
The ADCS-PACC composite score is used to assess cognitive decline
Concentration of proteins involved in Alzheimer disease [At inclusion and at 24 months]
Determination of Aβ42, Aβ40, Tau and P-Tau proteins in serum and cerebrospinal fluid
Concentration of orexinA/hypocretin [At inclusion and at 24 months]
Determination in serum and cerebrospinal fluid
Changes in sleep duration [At inclusion and at 24 months]
Average sleep duration (in hours and minutes) over a 14-day period from inclusion to M24 measured by actimetry
Sleep time at stage 1-2 during polysomnography [At inclusion and at 24 months]
Time spent in stage 1-2 sleep measured in hours and minutes during polysomnography
Sleep time at stage 3 during polysomnography [At inclusion and at 24 months]
Time spent in stage 3 sleep measured in hours and minutes during polysomnography
Time spent in Rapid eye movement (REM) sleep during polysomnography [At inclusion and at 24 months]
Time spent in stage 3 sleep measured in hours and minutes during polysomnography
Apnea Hypopnea Index [At inclusion and at 24 months]
The Apnea-Hypopnea Index is calculated from the number of apneas and hypopneas per hour of sleep (AHI = number of apneas + number of hypopneas / number of hours of sleep) during polysomnography
Nocturnal oxygen saturation (SaO2) [At inclusion and at 24 months]
The nocturnal SaO2 is an average of SaO2 values taken during the night. The value is expressed as a percentage and is measured during polysomnography
Urinary melatonin concentration [At inclusion and at 24 months]
Fractional diuresis
Internal temperature [At inclusion and at 24 months]
The internal temperature will be measured with an e-Celsius capsule during polysomnography

Eligibility Criteria

Criteria

Ages Eligible for Study:

50 Years to 85 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Diagnosis of mild Alzheimer's disease with a Mini Mental State (MMS) between 21-30
The presence of a family carer to complete neuropsychological scales, questionnaires and sleep diaries
Having a neurological assessment and/or follow-up requiring blood and cerebrospinal fluid (CSF) sampling with biomarkers for diagnostic purposes
Patient who had a lumbar puncture less than one year ago or patient with a scheduled lumbar puncture as part of care
Signed informed consent
Able to carry out all visits and follow study procedures
Affiliation to the French social security system

Exclusion Criteria:

Genetic form of alzheimer's disease
Insufficient clinical and paraclinical information for the diagnosis of AD
Anticholinesterase and/or memantine treatment or on stable doses for at least 3 months
Use of antidepressants, anxiolytics, hypnotics, neuroleptics, 15 days before inclusion
Patient living in a nursing home
Illiteracy or inability to perform psycho-behavioural tests
Major physical or neurosensory problems that may interfere with the tests
Initial contraindication to diagnostic lumbar puncture (LP) (spinal surgery, skin infection, haemostasis abnormality, intracranial hypertension, severe coagulation disorders, curative anticoagulant therapy, severe liver failure)
Refusal to perform a diagnostic lumbar puncture
Contraindication to the use of E-Celsius: people weighing less than 40 kg, with intestinal disorders, with known swallowing disorders
Patient deprived of liberty, by judicial or administrative decision;
Major protected by law;
Patient in a period of relative exclusion from another protocol or for whom the maximum annual compensation of €4500 has been reached;
Refusal to participate in the protocol.