Modulation of CSF Amyloid-beta Concentrations Via Behavioral Sleep Deprivation and Pharmacological Sleep Induction

Study Overview
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Brief Summary
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The purpose of this study is to change the concentration of amyloid-beta in human cerebrospinal fluid (CSF) through modulation of the sleep-wake cycle.

Detailed Description
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The purpose of this research study is to investigate whether or not increasing or decreasing duration of sleep over one night will change the concentration of amyloid-beta in cerebral spinal fluid (CSF).

Official Title
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Modulation of CSF Amyloid-beta Concentrations Via Behavioral Sleep Deprivation and Pharmacological Sleep Induction

Conditions
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Amyloid-beta

Intervention / Treatment
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* Drug: Sodium Oxybate
* Behavioral: Sleep deprivation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: cognitively normal or CDR 0 negative for amyloid deposition by PET Pittsburgh Compound-B (PIB) imaging or CSF amyloid-beta-42 concentration Age 18-60 Average reported sleep time 6-10hrs Exclusion Criteria: diagnosis of a sleep disorder such as sleep apnea, narcolepsy, or restless leg syndrome positive ambulatory sleep study for obstructive sleep apnea (AHI > 5 respiratory events per hour) that will be performed as part of initial screening prior to enrollment Clinical Dementia Rating (CDR) > 0 tremor or other neurologic injury in the non-dominant upper extremity (such as stroke or tremor) that would prevent the use of actigraphy current sleep walking or other sleep parasomnia diagnosis and treatment of stroke, myocardial infarction or heart attack, coronary artery disease, atrial fibrillation, or congestive heart failure diagnosis and treatment of asthma or Chronic Obstructive Pulmonary Disease (COPD) diagnosis and treatment of bipolar disorder, major depression, or Schizophrenia current urinary or fecal incontinence currently on a low salt diet diagnosis and treatment of a neurologic disorder such as Parkinson's disease, epilepsy, multiple sclerosis currently taking any blood thinner medications such as warfarin, Plavix, or Aspirin kidney disease resulting in renal impairment liver disease resulting in hepatic dysfunction Pregnancy currently taking sedating medications such as benzodiazepines alcohol use at bedtime tobacco use BMI >40 contraindication to lumbar puncture diabetes sleep schedule outside the range of bedtime: 8pm-12am and waketime 4am-8am self reported difficulty sleeping in an unfamiliar environment use of sedative-hypnotic medications inability to get in and out of bed history or presence of any clinically significant medical condition, behavioral or psychiatric disorder, or surgical history based on medical record or patient report history of drug abuse within the past 6 months positive score on 2 or more categories on the Berlin questionnaire participation in another investigational medicinal product or investigational device within the last 30 days

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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All

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: Other
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Sleep Induction<br>7.5 grams of sodium oxybate | Drug: Sodium Oxybate<br>* Sodium oxybate h.s.<br>* Other names: Xyrem;|
| Experimental: Sleep Deprivation<br>Sleep deprivation for up to 36 hours with no naps or other sleep periods | Behavioral: Sleep deprivation<br>* 36hr sleep deprivation<br>|
| No Intervention: Control<br>Participant will sleep as normal under the same controlled conditions in a clinical research unit | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent Increase From Mean Baseline (07:00 to 19:00) of Cerebrospinal Fluid (CSF) Amyloid Beta During Sleep Induction and Sleep Deprivation Between 01:00 and 11:00 From Baseline | Overnight (01:00 to 11:00) differences in CSF amyloid beta from baseline (07:00 to 19:00) between 1) sleep-deprived and control participants and 2) sleep-induced and control participants. | Baseline = 07:00 to 19:00; Intervention period = 01:00 to 11:00 |