Sleep Trial to Prevent Alzheimer's Disease

Study Overview
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Brief Summary
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The purpose of this study is to determine if treatment with the sleep aid suvorexant can decrease the rate of amyloid-β (Aβ) accumulation in the brain.

Detailed Description
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This study will investigate if long-term treatment with suvorexant will slow amyloid-β accumulation in the brain. Amyloid-β is a protein involved in the disease process leading to Alzheimer's disease. This study will evaluate if suvorexant can decrease the amount of amyloid-beta detected on brain scans (primary outcome).

Official Title
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Sleep Trial to Prevent Alzheimer's Disease

Conditions
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Sleep, Alzheimer Disease

Intervention / Treatment
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* Drug: Suvorexant 20 mg
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female. Any race or ethnicity. Participants must be age ≥65 years and able to sign informed consent. PET PIB standard uptake value ratio (SUVR) between ≥1.2 to ≤3. Global Clinical Dementia Rating (CDR) 0. Willing and able to undergo study procedures. Capacity to give informed consent and follow study procedures. Exclusion Criteria: Any sleep disorders other than insomnia, such as history or reported symptoms suggestive of restless legs syndrome, narcolepsy, or parasomnia. Actigraphic sleep efficiency ≥85%. Abnormal movement of the non-dominant arm (would affect actigraphy data in unpredictable ways). STOP-Bang score ≥ 5. Sleep disordered breathing if treated with PAP or AHI >15. Negative plasma amyloid-beta test Stroke. Chronic kidney disease defined as patients with markers of kidney damage or eGFR of < 60 ml/min/1.73m2. Hepatic impairment defined as AST and/or ALT > 2x upper limit of normal (normal limits AST: 11-47 IU/L, ALT: 6-53 IU/L). HIV/AIDS. Body mass index >35. History of substance abuse or alcoholism in the proceeding 6 months. History of regular alcohol consumption 3 or more days a week over the last 6 months. Regular alcohol consumption is defined as having more than 2 alcoholic beverages within 3 hours of bedtime. Participants that agree to reduce alcohol consumption during the study may not be excluded. History of presence of any clinically significant medical condition, behavioral or psychiatric disorder, or surgical history based on medical record or participant report that could affect the safety of the participant or interfere with study assessments or in the judgement of the Principal-Investigator (PI) if participant is not a good candidate. Has any medical condition that, in the PI's opinion, could increase risk to the participant, limit the participant's ability to tolerate the research procedures, or interfere with the collection/analysis of the data (e.g. participants with severe chronic back pain might not be able to lie still during the scanning procedures). Potential medical conditions that will be exclusionary at the PI's discretion: Cardiovascular disease requiring medication except for controlled hypertension. Pulmonary disease. Type I diabetes. Neurologic or psychiatric disorder requiring medication. Tobacco use. Use of sedating medications. Use of medications that interact with suvorexant (if cannot be discontinued) Abnormal safety labs History of current suicidal ideations. Contraindications to PET, CT, or MRI (e.g. electronic medical devices, inability to lie still for extended periods) that make it unsafe for the individual to participate. All participants will be screened and excluded for neurologic or psychiatric co-morbidities that could affect cognition as well as medical co-morbidities that may prevent participants from undergoing PET/MRI, or cause excessive motion during scanning. Has hypersensitivity to AV-1451 and PIB or any of its excipients. Severe claustrophobia. Currently pregnant or breast-feeding. Women must agree to avoid becoming pregnant and must agree to refrain from sexual activity or to use reliable contraceptive methods for 24 hours following administration of Flortaucipir injection. In the opinion of the PI, the participant should be excluded due to an abnormal physical examination. Must not have participated in any clinical trial involving a study drug or device within the 30-days prior to study enrollment. Must not participate in another drug or device study prior to the end of this study participation. Current or recent (within 12 months prior to screening) participation in research studies involving radioactive agents such that the total research-related radiation dose to the participant in any given year would exceed the limits set forth in the U.S. Code of Federal Regulations (CFR) Title 21 Section 361.1. Exclusion criteria for optional lumbar punctures -• Contraindication to lumbar puncture (anticoagulants; bleeding disorder; allergy to lidocaine or disinfectant; prior central nervous system or lower back surgery).

Ages Eligible for Study
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Minimum 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: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Poor sleep treatment group<br>100 participants will be randomized to take suvorexant 20mg daily at h.s. for two years | Drug: Suvorexant 20 mg<br>* Suvorexant 20mg will be taken nightly for 24 months.<br>* Other names: Belsomra;|
| Placebo Comparator: Poor sleep control grop<br>100 participants will be randomized to take placebo daily at h.s. for two years. | Drug: Placebo<br>* Placebo will be taken nightly for 24 months.<br>* Other names: sugar pill;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Amyloid-β accumulation detected by brain scans compared to placebo | PET | 24 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in tau accumulation detected by brain scans compared to placebo | PET | 24 months | 
| Change in plasma Amyloid-β compared to placebo | Blood collection | 24 months | 
| Change in CSF Amyloid-β compared to placebo | Cerebrospinal fluid collection | 24 months | 
| Change in plasma tau compared to placebo | Blood collection | 24 months | 
| Change in CSF tau compared to placebo | Cerebrospinal fluid collection | 24 months | 
| Change in plasma p-tau compared to placebo | Blood collection | 24 months | 
| Change in CSF p-tau compared to placebo | Cerebrospinal fluid collection | 24 months | 
| Change in cognitive performance compared to placebo | Measured by a cognitive composite consisting of the Digit Symbol Substitution Test, Animal Naming, Trails B and the Free and Cued Selective Reminding Test. Each test will be z-scored and then averaged together to make the composite. | 24 months | 
| Change in transcriptomics compared to placebo | blood and optional CSF collection | 24 months | 
| Change in metabolomics compared to placebo | blood and optional CSF collection | 24 months | 
| Change in proteomics compared to placebo | blood and optional CSF collection | 24 months | 
| Change in gut microbiome compared to placebo | optional stool sample collection | 214 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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poor sleep, Amyloid-Beta, Insomnia