Investigating a sleep aid for reducing Alzheimer's disease biomarkers
Effect of a Dual Orexin Receptor Antagonist on CSF Alzheimer's Disease Biomarkers
This study is testing whether a new sleep aid can lower certain Alzheimer's-related proteins in the blood of older adults who are at risk for the disease.
Quick facts
| Phase | Phase 2 |
|---|---|
| Study type | Interventional |
| Enrollment | 201 (estimated) |
| Ages | 65 Years and up |
| Sex | All |
| Sponsor | Washington University School of Medicine Academic / other |
| Locations | 1 site (St Louis, Missouri) |
| Trial ID | NCT06274528 on ClinicalTrials.gov |
What this trial studies
This clinical trial aims to evaluate the effectiveness of lemborexant, a dual orexin receptor antagonist, in decreasing amyloid-beta and tau proteins in the blood of cognitively normal older adults with amyloid deposition. The study will assess the impact of enhanced sleep over six months on various Alzheimer's disease biomarkers, including phosphorylated tau and neurodegeneration markers. Participants will receive either lemborexant at two different doses or a placebo, and the trial will also monitor the safety and pharmacokinetics of the drug. The goal is to provide insights into the potential biological effectiveness of lemborexant in this population.
Who should consider this trial
Good fit: Ideal candidates are cognitively normal older adults aged 65 and above with amyloid deposition.
Not a fit: Patients with untreated sleep apnea, significant renal or hepatic impairment, or a negative plasma amyloid-beta and tau test may not benefit from this study.
Why it matters
Potential benefit: If successful, this study could lead to new therapeutic strategies for reducing Alzheimer's disease biomarkers and potentially delaying the onset of the disease.
How similar studies have performed: While the approach of using sleep aids in Alzheimer's research is emerging, this specific application of lemborexant is novel and has not been extensively tested in prior studies.
Eligibility criteria
Show full inclusion / exclusion criteria
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 or reported symptoms suggestive of restless legs syndrome, narcolepsy, or parasomnia. * STOP-Bang score \>6 for participants without PAP. * Untreated sleep apnea AHI\>15 * Poorly treated sleep apnea due to noncompliance or an AHI ≥ 10. \- PAP compliance is defined as ≥ 4 hours per night \>70% of the nights. * Plasma p-Tau217/np-Tau217% \<2.5 * Stroke. * History of renal impairment * Defined as older adult patients with markers of kidney damage or eGFR \< 45.0 ml/min/1.73m2. * Normal Limits ≥ 45.0 mL/min/1.73m2 * History of hepatic impairment * AST and/or ALT ≥ 2X upper limit of normal (ULN). * Normal Limits: AST 11-47 IU/L and ALT 6-53 IU/L * HIV/AIDS. * History of substance abuse or alcohol abuse in the preceding 6 months. * 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 or study team investigator'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 or study team investigator's discretion: * Cardiovascular disease requiring medication except for controlled hypertension. * Pulmonary disease. * Type I diabetes. * Neurologic or psychiatric disorder requiring medication. * Untreated depression * Tobacco use. * Use of sedating medications. * Use of medications that interact with lemborexant (if cannot be discontinued). * Abnormal safety labs. * History of current suicidal ideations. * Inability to speak and understand English. * 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. Optional assessment exclusion criteria: • Contraindication to lumbar puncture (anticoagulants; bleeding disorder; allergy to lidocaine or disinfectant; prior central nervous system or lower back surgery).
Where this trial is running
St Louis, Missouri
- Washington University in St. Louis, School of Medicine — St Louis, Missouri, United States (Recruiting)
Study contacts
- Principal investigator: Brendan Lucey, MD — Washington University School of Medicine
- Study coordinator: Chloe Meehan, MA
- Email: cmeehan@wustl.edu
- Phone: 314-273-0878
How to participate
- Review the eligibility criteria above with your treating physician.
- Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
- Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.