Acute Effect of Lemborexant on CSF Amyloid-Beta and Tau

Study Overview
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Brief Summary
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This study will look at the effects of lemborexant on Alzheimer's disease biomarkers found in the cerebrospinal fluid (CSF) and blood in individuals who are poor sleepers

Detailed Description
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This study will determine the acute effect of lemborexant on CNS tau phosphorylation and other Alzheimer's disease biomarkers in individuals with poor sleep quality.

Official Title
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Acute Effect of Lemborexant on CSF Amyloid-Beta and Tau

Conditions
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Alzheimer Disease

Intervention / Treatment
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* Drug: Lemborexant 25 mg
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 60-80 years Any sex Any race/ethnicity Mini-Mental Status Examination score (MMSE) ≥ 27 Positive plasma amyloid-beta test (i.e., amyloid-positive) Pittsburgh Sleep Quality Index >5 Exclusion Criteria: Cognitive impairment as determined by history of MMSE < 27 Inability to speak or understand English Any sleep disorders other than insomnia No history of moderate-to-severe sleep-disordered breathing and STOP-Bang score > 5 History or reported symptoms suggestive of restless legs syndrome, narcolepsy or other sleep disorders No more than mild sleep apnea (AHI <16) on PSG Sleep schedule outside the range of bedtime 22:00-midnight 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) Suicidal ideations Alcohol, tobacco or marijuana use (PI discretion) Use of sedating medications (PI discretion) Inability to get out of bed independently In the opinion of the investigator, the participant should be excluded due to an abnormal physical examination. Current pregnancy Body Mass Index >35 History of migraines (PI discretion) History of drug abuse in the last 6 months History or presence of any clinically significant medical condition, behavioral or psychiatric disorder (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 participant is not a good candidate. Urinary or fecal incontinence Concurrently enrolled in another trial of an investigational drug or device

Ages Eligible for Study
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Minimum Age: 60 Years
Maximum Age: 80 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: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: treatment<br>20 participants will be randomized to take lemborexant 25mg at h.s for two consecutive nights | Drug: Lemborexant 25 mg<br>* Lemborexant 25mg will be taken nightly for two consecutive nights.<br>* Other names: Dayvigo;|
| Placebo Comparator: placebo<br>10 participants will be randomized to take placebo at h.s. for two consecutive nights. | Drug: Placebo<br>* Placebo will be taken nightly for two consecutive nights<br>* Other names: sugar pil;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in CNS tau phosphorylation | Changes in CSF pT181/T181 ratio compared to placebo | 48 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in other CSF AD biomarkers | Changes in CSF pS202/S202, pT217/T217, and amyloid-beta | 48 hours | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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poor sleep