Back to resultsBiomarkers of Sleep-wake Cycle in Prodromal Alzheimer's Disease: Role in Cognitive Decline? (ALZ-OREX)
Primary Purpose
Neuropathology
Status
Not yet recruiting
Phase
Not Applicable
Locations
France
Study Type
Interventional
Intervention
Polysomnography
Neuropsychological assessment
Questionnaires on sleep and behavioural problems
Actimetry
Fractional diuresis
Internal temperature measurement
Biomarker assay
Sponsored by
About this trial
This is an interventional diagnostic trial for Neuropathology focused on measuring cognitive composite score, sleep, biomarkers, cognitive decline
Eligibility Criteria
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.
Sites / Locations
- University Hospital, Montpellier
- University Hospital of Poitiers
- University Hospital of Toulouse
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Single arm
Arm Description
Alzheimer
Outcomes
Primary Outcome Measures
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
Secondary Outcome Measures
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
Cognitive decline in ADCS-PACC composite score
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
The ADCS-PACC composite score is used to assess cognitive decline
Concentration of proteins involved in Alzheimer disease
Determination of Aβ42, Aβ40, Tau and P-Tau proteins in serum and cerebrospinal fluid
Concentration of orexinA/hypocretin
Determination in serum and cerebrospinal fluid
Changes in sleep duration
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
Time spent in stage 1-2 sleep measured in hours and minutes during polysomnography
Sleep time at stage 3 during polysomnography
Time spent in stage 3 sleep measured in hours and minutes during polysomnography
Time spent in Rapid eye movement (REM) sleep during polysomnography
Time spent in stage 3 sleep measured in hours and minutes during polysomnography
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
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
Urinary melatonin concentration
Fractional diuresis
Internal temperature
The internal temperature will be measured with an e-Celsius capsule during polysomnography
Full Information
NCT ID
NCT05629871
First Posted
October 28, 2022
Last Updated
January 12, 2023
Sponsor
University Hospital, Montpellier
Collaborators
Institut National de la Santé Et de la Recherche Médicale, France
1. Study Identification
Unique Protocol Identification Number
NCT05629871
Brief Title
Biomarkers of Sleep-wake Cycle in Prodromal Alzheimer's Disease: Role in Cognitive Decline?
Acronym
ALZ-OREX
Official Title
Biomarkers of Sleep-wake Cycle in Prodromal Alzheimer's Disease: Role in Cognitive Decline?
Study Type
Interventional
2. Study Status
Record Verification Date
December 2022
Overall Recruitment Status
Not yet recruiting
Study Start Date
March 15, 2023 (Anticipated)
Primary Completion Date
June 1, 2027 (Anticipated)
Study Completion Date
June 1, 2027 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University Hospital, Montpellier
Collaborators
Institut National de la Santé Et de la Recherche Médicale, France
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. 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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Neuropathology
Keywords
cognitive composite score, sleep, biomarkers, cognitive decline
7. Study Design
Primary Purpose
Diagnostic
Study Phase
Not Applicable
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
132 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Single arm
Arm Type
Experimental
Arm Description
Alzheimer
Intervention Type
Procedure
Intervention Name(s)
Polysomnography
Intervention Description
Polysomnography will be performed for 24 hours at inclusion and 24 months
Intervention Type
Behavioral
Intervention Name(s)
Neuropsychological assessment
Intervention Description
A full neuropsychological assessment will be performed at inclusion, 12 and 24 months
Intervention Type
Behavioral
Intervention Name(s)
Questionnaires on sleep and behavioural problems
Intervention Description
Questionnaires on sleep and behavioural problems
Intervention Type
Procedure
Intervention Name(s)
Actimetry
Intervention Description
Measurement of actimetrics for 14 days at inclusion and at 24 months
Intervention Type
Diagnostic Test
Intervention Name(s)
Fractional diuresis
Intervention Description
Split diuresis from 7pm-7am, 7am-12am and 12pm-19pm during polysomnography at inclusion inclusion and 24 months to measure melatonin concentration
Intervention Type
Procedure
Intervention Name(s)
Internal temperature measurement
Intervention Description
eCelsius capsule to measure internal temperature at inclusion and 24 months
Intervention Type
Other
Intervention Name(s)
Biomarker assay
Intervention Description
Determination of the biomarkers Aβ42, Aβ40, Tau and P-Tau in blood and in the cerebrospinal fluid
Primary Outcome Measure Information:
Title
Change in the Free and Cued Selective Reminding Test (FCSRT) scale score
Description
The FCSRT test evaluates memory, the score obtained is between 0 and 48, higher score mean a better outcome
Time Frame
From inclusion to 24 months
Secondary Outcome Measure Information:
Title
Change in the Free and Cued Selective Reminding Test (FCSRT) scale score
Description
The FCSRT test evaluates memory, the score obtained is between 0 and 48, higher score mean a better outcome
Time Frame
From inclusion to 12 months
Title
Cognitive decline in ADCS-PACC composite score
Description
The ADCS-PACC composite score is used to assess cognitive decline
Time Frame
At inclusion and at 24 months
Title
Cognitive decline in the Alzheimer's Disease Cooperative Study- Preclinical Alzheimer Cognitive Composite (ADCS-PACC) composite score
Description
The ADCS-PACC composite score is used to assess cognitive decline
Time Frame
At inclusion and at 12 months
Title
Concentration of proteins involved in Alzheimer disease
Description
Determination of Aβ42, Aβ40, Tau and P-Tau proteins in serum and cerebrospinal fluid
Time Frame
At inclusion and at 24 months
Title
Concentration of orexinA/hypocretin
Description
Determination in serum and cerebrospinal fluid
Time Frame
At inclusion and at 24 months
Title
Changes in sleep duration
Description
Average sleep duration (in hours and minutes) over a 14-day period from inclusion to M24 measured by actimetry
Time Frame
At inclusion and at 24 months
Title
Sleep time at stage 1-2 during polysomnography
Description
Time spent in stage 1-2 sleep measured in hours and minutes during polysomnography
Time Frame
At inclusion and at 24 months
Title
Sleep time at stage 3 during polysomnography
Description
Time spent in stage 3 sleep measured in hours and minutes during polysomnography
Time Frame
At inclusion and at 24 months
Title
Time spent in Rapid eye movement (REM) sleep during polysomnography
Description
Time spent in stage 3 sleep measured in hours and minutes during polysomnography
Time Frame
At inclusion and at 24 months
Title
Apnea Hypopnea Index
Description
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
Time Frame
At inclusion and at 24 months
Title
Nocturnal oxygen saturation (SaO2)
Description
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
Time Frame
At inclusion and at 24 months
Title
Urinary melatonin concentration
Description
Fractional diuresis
Time Frame
At inclusion and at 24 months
Title
Internal temperature
Description
The internal temperature will be measured with an e-Celsius capsule during polysomnography
Time Frame
At inclusion and at 24 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
50 Years
Maximum Age & Unit of Time
85 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Yves Dauvilliers, MD
Phone
+33467335219
Email
y-dauvilliers@chu-montpellier.fr
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Karim BENNYS, MD
Organizational Affiliation
University Hospital, Montpellier
Official's Role
Principal Investigator
Facility Information:
Facility Name
University Hospital, Montpellier
City
Montpellier
Country
France
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Karim BENNYS, MD
First Name & Middle Initial & Last Name & Degree
Karim BENNYS, MD
Facility Name
University Hospital of Poitiers
City
Poitiers
Country
France
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Marc PACCALIN, MD
First Name & Middle Initial & Last Name & Degree
Marc PACCALIN
Facility Name
University Hospital of Toulouse
City
Toulouse
Country
France
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Rachel DEBS, MD
First Name & Middle Initial & Last Name & Degree
Rachel DEBS, MD
12. IPD Sharing Statement
Learn more about this trial
Biomarkers of Sleep-wake Cycle in Prodromal Alzheimer's Disease: Role in Cognitive Decline?
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