Acute Effect of Lemborexant on CSF Amyloid-Beta and Tau

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

Study Overview

• Status: Withdrawn
• Conditions: Alzheimer Disease
• Intervention / Treatment: Drug: Placebo; Drug: Lemborexant 25 mg

Detailed Description

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.

• Study Type: Interventional
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Washington University School of Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 60 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

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

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: treatment; 20 participants will be randomized to take lemborexant 25mg at h.s for two consecutive nights	Drug: Lemborexant 25 mg; Lemborexant 25mg will be taken nightly for two consecutive nights.; Other Names: Dayvigo
Placebo Comparator: placebo; 10 participants will be randomized to take placebo at h.s. for two consecutive nights.	Drug: Placebo; Placebo will be taken nightly for two consecutive nights; Other Names: inactive pill; sugar pil

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Brendan Lucey
• Collaborators: Eisai Inc.
• Investigators: Principal Investigator: Brendan Lucey, MD, Washington University School of Medicine

Study record dates

Study Major Dates

• Study Start (Actual): March 1, 2023
• Primary Completion (Actual): September 27, 2023
• Study Completion (Actual): October 4, 2023

Study Registration Dates

• First Submitted: February 5, 2023
• First Submitted That Met QC Criteria: February 5, 2023
• First Posted (Actual): February 15, 2023

Study Record Updates

• Last Update Posted (Actual): November 8, 2023
• Last Update Submitted That Met QC Criteria: November 3, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Keywords: 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; Lemborexant
• Other Study ID Numbers: HRPO 202210049

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No