Effects of Sleep Deprivation on Cerebrospinal Fluid (CSF) Amyloid-beta (Aβ) Dynamics

Study Overview
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Brief Summary
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Introduction: Alzheimer's disease (AD) is characterized by neurodegeneration of the brain in the form of neurofibrillary tangles and plaques containing the amyloid-beta protein (Abeta). Recent animal studies have shown that extended wakefulness is associated with increased production of these Abeta proteins and that sleep leads to a marked fall in their production. Aim: The investigators aim to distinguish a similar effect of sleep disturbance on cerebrospinal fluid (CSF) Abeta levels in humans, which may point out sleep disturbance as an important factor in AD development. Methods: a study in 26 healthy male volunteers, measuring CSF Abeta levels during a sleep deprivation night and before and after a control night with unrestricted sleep. Expected results: The investigators expect sleep deprivation to lead to an increase in CSF Abeta levels, as compared to the levels in the control night.

Official Title
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Losing Sleep Over Alzheimer's Disease? Effects of Sleep Deprivation on Cerebrospinal Fluid Amyloid-beta Dynamics

Conditions
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Alzheimer Disease

Intervention / Treatment
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* Behavioral: Sleep deprivation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Written informed consent Age 40-60 years Male Subject is in good health as established by medical history, physical examination, ECG and laboratory examination Laboratory parameters (as described on in section 3.7 screening) should be within the normal ranges as applicable in RUNMC, Nijmegen, or clinically acceptable to the investigator Normal sleep behaviour, Pittsburg Sleep Quality index score ≤5 MMSE 28 or higher Medication free Exclusion Criteria: Presence of blood coagulopathy, established by medical history Allergy to local anesthetic agents Contra-indication for spinal catheter placement: medical history of compression of spinal cord, spinal surgery, skin infection, developmental abnormalities in lower spine Subjects who are currently participating in another study or have participated in a clinical study within 30 days, based on their own report about participation history Subjects with a history of drug or alcohol abuse Subjects who are part of the study staff personnel or family members of the study staff personnel

Ages Eligible for Study
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Minimum Age: 40 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Sleep deprivation<br>13 subjects will undergo full sleep deprivation these subjects are blind to allocation ntil they enter the study center | Behavioral: Sleep deprivation<br>* subjects will undergo one night of full sleep deprivation<br>|
| No Intervention: Control night<br>control night of unrestricted sleep in 13 other subjects | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Amyloid beta | Subjects will undergo one night of sleep deprivation before, during and after which a total of 9 CSF samples (6ml each) will be drawn through a spinal catheter. From these CSF samples Amyloid beta will be analysed. | 6 timepoints during one night of sleep deprivation | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Alzheimer Disease, Cerebrospinal fluid, Sleep, Abeta