Sleep Trial to Prevent Alzheimer's Disease (SToP-AD)

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.

Study Overview

• Status: Recruiting
• Conditions: Sleep; Alzheimer Disease
• Intervention / Treatment: Drug: Suvorexant 20 mg; Drug: Placebo

Detailed Description

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).

• Study Type: Interventional
• Enrollment (Estimated): 200
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Cristina Toedebusch, BS; Phone Number: 3147470646; Email: toedebuschc@wustl.edu
• Study Contact Backup: Name: Chloe Meehan, MA; Phone Number: 3142730878; Email: cmeehan@wustl.edu

Study Locations

• United States
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Recruiting
      • Washington University School of Medicine
      • Contact: Cristina Toedebusch, BS; Phone Number: 314-747-0646; Email: toedebuschc@wustl.edu
      • Principal Investigator: Brendan Lucey, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 65 years and older (Older Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Male or female.
• Any race or ethnicity.
• Participants must be age ≥65 years and able to sign informed consent.
• Global Clinical Dementia Rating (CDR) 0.
• Willing and able to undergo study procedures.

Exclusion Criteria:

• History of reported symptoms suggestive of restless legs syndrome, narcolepsy or other central disorder of hypersomnolence, or parasomnia
• Actigraphic sleep efficiency ≥85%.
• Abnormal movement of the non-dominant arm (would affect actigraphy data in unpredictable ways).
• STOP-Bang score ≥ 5.
• Untreated OSA with AHI ≥15 on home sleep test

• Treated sleep apnea with PAP non-compliance

  • PAP compliance is defined as >= 4 hours per night >70% of the nights
• Plasma A-beta and tau test with a plasma p-tau 217% ≤0.82
• 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. 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.
• Currently pregnant or breast-feeding.
• 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.

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).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Amyloid-β accumulation detected by plasma pT217/T217 compared to placebo	Blood collection	24 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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

Collaborators and Investigators

• Sponsor: Washington University School of Medicine
• Collaborators: Merck Sharp & Dohme LLC; Good Ventures Foundation
• Investigators: Principal Investigator: Brendan Lucey, MD, Washington Univeristy School of Medicine

Study record dates

Study Major Dates

• Study Start (Actual): May 25, 2022
• Primary Completion (Estimated): May 1, 2026
• Study Completion (Estimated): May 1, 2026

Study Registration Dates

• First Submitted: November 9, 2020
• First Submitted That Met QC Criteria: November 9, 2020
• First Posted (Actual): November 16, 2020

Study Record Updates

• Last Update Posted (Actual): March 27, 2024
• Last Update Submitted That Met QC Criteria: March 25, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: Insomnia; Amyloid-Beta; poor sleep
• Additional Relevant MeSH Terms: Mental Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurocognitive Disorders; Neurodegenerative Diseases; Dementia; Tauopathies; Alzheimer Disease; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Hypnotics and Sedatives; Sleep Aids, Pharmaceutical; Orexin Receptor Antagonists; Suvorexant
• Other Study ID Numbers: 2020008007

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes