DORA and LP in Alzheimer's Disease Biomarkers

Phase 2

Recruiting

• Conditions: Alzheimer Disease
• Interventions: Drug: Lemborexant 20mg; Drug: Placebo; Drug: Lemborexant 10 mg

• Registration Number: NCT06274528
• Lead Sponsor: Washington University School of Medicine

Brief Summary

The purpose of this study is to see if the sleep aid, lemborexant, can decrease the amount of amyloid-beta and tau in the blood. Amyloid-beta and tau are proteins involved in the disease process leading to Alzheimer's disease.

Detailed Description

The overall goal of this project is to conduct an early stage (phase II) clinical trial of a dual orexin receptor antagonist (DORA), lemborexant, in cognitively normal older adults with amyloid deposition to demonstrate the feasibility and potential biological effectiveness of lemborexant's target engagement with multiple blood plasma and cerebrospinal fluid...

Basic Information
|
Recruitment & Eligibility
|
Study & Design
|
Trial Locations

Study Timeline

• Study First Submitted: 2024-01-29
• Study First Submitted QC: 2024-02-15
• Study First Posted: 2024-02-23
• Study Start: 2024-03-11
• Status Verified: 2024-11
• Last Update Submitted: 2024-11-25
• Last Update Posted: 2024-11-27
• Primary Completion: 2029-03-11
• Study Completion: 2029-03-11

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 201

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.

Read More

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.

• Negative plasma amyloid-beta and tau test

• 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).

Read More

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Lemborexant 20 mg	Lemborexant 20mg	Lemborexant is a capsule, taken by mouth once a night, approximately 30 minutes prior to bed for 6 months.
Placebo	Placebo	Placebo is in capsule form and contains an inactive substance. It is taken by mouth once a night, approximately 30 minutes prior to bed for 6 months.
Lemborexant 10 mg	Lemborexant 10 mg	Lemborexant is a capsule, taken by mouth once a night, approximately 30 minutes prior to bed for 6 months.

Primary Outcome Measures

Name	Time	Method
Changes plasma pT181/T181 ratio of lemborexant 10 and 20 mg compared to Placebo	6 months	plasma collection

Secondary Outcome Measures

Name	Time	Method
Measure changes of blood plasma p-tau/tau forms (T181, pT181, pT181/T181, S202, pS202, pS202/S202, T217, pT217, pT217/T217).	6 months	Blood collection
Number of participants with treatment-related adverse events	6 months	Adverse events
Measure the blood concentration of lemborexant 10 mg and 20 mg and determine the dose-response relationship with CSF pT181/T181	6 months	Blood collection
Measure changes on blood plasma amyloid-beta isoforms (Aβ38, Aβ40, Aβ42, Aβ42/Aβ40)	6 months	Blood collection
Measure changes of CSF amyloid beta isoforms (Aβ38, Aβ40, Aβ42,Aβ42/Aβ40 )	6 months	CSF collection
Measure changes of cerebrospinal fluid p-tau/tau forms (T181, pT181, S202, pS202, pS202/S202, T217, pT217, pT217/T217).	6 months	CSF collection

Trial Locations

Locations (1)

Washington University in St. Louis, School of Medicine; 🇺🇸 Saint Louis, Missouri, United States