Sleep Quality and Amyloid-Beta Kinetics

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) by modification of sleep efficiency.

Detailed Description
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The purpose of the study is to investigate whether or not increasing sleep efficiency will change the concentration of amyloid-beta in cerebrospinal fluid (CSF).

Official Title
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Sleep Quality and Amyloid-Beta Kinetics

Conditions
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Amyloid-beta

Intervention / Treatment
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* Drug: Suvorexant
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 45-65 years Any sex Any race/ethnicity Mini-Mental Status Examination score (MMSE) >=27 Sleep efficiency measured by actigraphy to determine good sleeper or poor sleeper Exclusion Criteria: Cognitive impairment as determined by history of MMSE < 27 Inability to speak or understand English BMI >35 Any sleep disorders other than insomnia history of sleep-disordered breathing STOP-Bang score > 3 History or reported symptoms suggestive of restless legs syndrome, narcolepsy or other sleep disorders Sleep schedule outside the range of bedtime 8PM-12AM and wake time 4AM-9AM Contraindication to lumbar catheter (anticoagulants; bleeding disorder; allergy to lidocaine or disinfectant; prior central nervous system or lower back surgery) Cardiovascular disease requiring medication except for controlled hypertension (PI discretion) Stroke Hepatic or renal impairment Pulmonary disease (PI discretion) Type 1 diabetes HIV or AIDS Neurologic or psychiatric disorder requiring medication (PI discretion) Alcohol or tobacco use (PI discretion) Use of sedating medications Inability to get out of bed independently Abnormal movement of the non-dominant arm (would affect actigraphy data in unpredictable ways) Abnormal physical examination Current pregnancy History of migraine headaches (PI discretion) History of drug abuse in the past 6 months Urinary or fecal incontinence Difficulty sleeping in an unfamiliar environment (good sleep quality group only) History or presence of any clinically significant medication condition, behavioral or psychiatric condition (including suicidal ideation), or surgical history based on medical record or patient report that could affect the safety of the subject or interfere with study assessments or in the judgment of the PI is not a good candidate

Ages Eligible for Study
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Minimum Age: 45 Years
Maximum Age: 65 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: Poor sleep group treatment 1<br>10mg Suvorexant tablet h.s. for two consecutive nights | Drug: Suvorexant<br>* Participants will be given a sleep aid (10mg or 20mg suvorexant) at bedtime for two consecutive nights that they are spending in a research unit.<br>* Other names: Belsomra;|
| Placebo Comparator: Poor sleep group control<br>Participant will receive placebo for two consecutive nights and sleep as normal under the same controlled conditions in a clinical research unit. | Drug: Placebo<br>* Participants will be given a placebo at bedtime for two consecutive nights that they are spending in a research unit.<br>* Other names: sugar pill;|
| Placebo Comparator: Good sleep group<br>Participant will receive placebo for two consecutive nights and sleep as normal under the same controlled conditions in a clinical research unit. | Drug: Placebo<br>* Participants will be given a placebo at bedtime for two consecutive nights that they are spending in a research unit.<br>* Other names: sugar pill;|
| Experimental: Poor sleep group treatment 2<br>20mg Suvorexant tablet h.s. for two consecutive nights | Drug: Suvorexant<br>* Participants will be given a sleep aid (10mg or 20mg suvorexant) at bedtime for two consecutive nights that they are spending in a research unit.<br>* Other names: Belsomra;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Difference in Amyloid-beta (Abeta) Concentration in the CSF (Cerebral Spinal Fluid) of Individuals With Poor Sleep Efficiency Compared to Those With Good Sleep Efficiency as Measured by ng/ml | Mean difference in amyloid-beta-42 concentration between individuals with poor sleep efficiency (Poor sleep group control) compared to those with good sleep efficiency (Good sleep group) | 36 hours of CSF collection | 
| Difference in Amyloid-beta (Abeta) Concentration in the CSF (Cerebral Spinal Fluid) of Individuals With Poor Sleep Efficiency Treated With Placebo, Suvorexant 10 mg, or Suvorexant 20 mg as Measured by ng/ml | Mean difference in amyloid-beta-42 concentration between individuals with poor sleep efficiency who were treated with placebo (Poor sleep group control), Suvorexant 10 mg (Poor sleep group treatment 1), and Suvorexant 20 mg (Poor sleep group treatment 2) | 36 hours of CSF collection |