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

Neuropathology Clinical Trial

— ALZ-OREX  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05629871
• Other study ID #: RECHMPL18_0061
• Status: Recruiting
• Phase: N/A
• Start date: April 17, 2023
• Est. completion date: July 1, 2027

Study information

• Verified date: May 2024
• Source: University Hospital, Montpellier
• Contact: Claire Denis
• Phone: +33467333162
• Email: claire-denis[@]chu-montpellier.fr
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 132
• Est. completion date: July 1, 2027
• Est. primary completion date: July 1, 2027
• Accepts healthy volunteers: No
• Gender: All
• Age group: 50 Years to 85 Years

Eligibility

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.

Related Conditions & MeSH terms

• Alzheimer Disease
• Cognitive Dysfunction
• Neuropathology

Intervention

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
• 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 Aß42, Aß40, Tau and P-Tau in blood and in the cerebrospinal fluid

Locations

Country	Name	City	State
France	University Hospital, Montpellier	Montpellier
France	University Hospital of Poitiers	Poitiers
France	University Hospital of Toulouse	Toulouse

Sponsors (2)

Lead Sponsor	Collaborator
University Hospital, Montpellier	Institut National de la Santé Et de la Recherche Médicale, France

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in the Free and Cued Selective Reminding Test (FCSRT) scale score	The FCSRT test evaluates memory, the score obtained is between 0 and 48, higher score mean a better outcome	From inclusion to 24 months
Secondary	Change in the Free and Cued Selective Reminding Test (FCSRT) scale score	The FCSRT test evaluates memory, the score obtained is between 0 and 48, higher score mean a better outcome	From inclusion to 12 months
Secondary	Cognitive decline in ADCS-PACC composite score	The ADCS-PACC composite score is used to assess cognitive decline	At inclusion and at 24 months
Secondary	Cognitive decline in the Alzheimer's Disease Cooperative Study- Preclinical Alzheimer Cognitive Composite (ADCS-PACC) composite score	The ADCS-PACC composite score is used to assess cognitive decline	At inclusion and at 12 months
Secondary	Concentration of proteins involved in Alzheimer disease	Determination of Aß42, Aß40, Tau and P-Tau proteins in serum and cerebrospinal fluid	At inclusion and at 24 months
Secondary	Concentration of orexinA/hypocretin	Determination in serum and cerebrospinal fluid	At inclusion and at 24 months
Secondary	Changes in sleep duration	Average sleep duration (in hours and minutes) over a 14-day period from inclusion to M24 measured by actimetry	At inclusion and at 24 months
Secondary	Sleep time at stage 1-2 during polysomnography	Time spent in stage 1-2 sleep measured in hours and minutes during polysomnography	At inclusion and at 24 months
Secondary	Sleep time at stage 3 during polysomnography	Time spent in stage 3 sleep measured in hours and minutes during polysomnography	At inclusion and at 24 months
Secondary	Time spent in Rapid eye movement (REM) sleep during polysomnography	Time spent in stage 3 sleep measured in hours and minutes during polysomnography	At inclusion and at 24 months
Secondary	Apnea Hypopnea Index	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	At inclusion and at 24 months
Secondary	Nocturnal oxygen saturation (SaO2)	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	At inclusion and at 24 months
Secondary	Urinary melatonin concentration	Fractional diuresis	At inclusion and at 24 months
Secondary	Internal temperature	The internal temperature will be measured with an e-Celsius capsule during polysomnography	At inclusion and at 24 months