Daridorexant for Alzheimer Disease Prevention

Официальное название

Double Blind Clinical Trial of Daridorexant (Dual Orexin Receptor Antagonist) for Alzheimer Disease Prevention

Обзор

This study will evaluate whether daridorexant, a DORA sleep medication, can support brain health by promoting the clearance of proteins linked to the development and progression of Alzheimer's disease. The trial is preventive and is open to participants who do not have Alzheimer's disease dementia, regardless of whether or not they experience sleep problems.

Подробное описание

Alzheimer's disease (AD) begins decades before symptoms with the accumulation of amyloid plaques and tau tangles, and interventions that slow or prevent this process could greatly reduce its impact. Dual orexin receptor antagonists (DORAs), drugs developed for insomnia, may help clear amyloid and tau, reduce neuroinflammation, and improve cognition through mechanisms that could be both related and unrelated to sleep quality. Early animal and human studies suggest that DORAs can alter biomarkers of Alzheimer's pathology making the orexin pathway modulation a promising strategy for Alzheimer's prevention. Daridorexant, one of the two DORAs available in Canada, stands out as a well-tolerated candidate for prevention due to its safety profile.

We want to evaluate the potential of Daridorexant for prevention of AD in this single-site, double-blind, randomized (1:1), placebo-controlled trial evaluating 50 mg of daridorexant versus placebo over 12 months in 240 participants. The primary biological outcome is the change from baseline to 12 months in the plasma ratio of phosphorylated tau181 to unphosphorylated tau181 (p-tau181/np-tau181). Secondary outcomes include changes in additional plasma biomarkers, cognitive performance, sleep parameters, and safety measures.

Вмешательства

• Препарат Daridorexant 50 mg
  Study drug (Daridorexant 50 mg) taken orally each night 30 minutes before bedtime, for the 1 year duration of the study
• Препарат Placebo
  Study drug (Placebo) will be taken orally each night, 30 minutes before bedtime, for the 1 year duration of the study

Первичные конечные точки

• Change in plasma p-tau217/np-tau217 ratio [Срок оценки: baseline up to estimated 12 months]

Вторичные конечные точки (4)

• Change in plasma p-tau181/np-tau181 ratio [Срок оценки: baseline up to estimated 12 months]
• Change in plasma Aβ42/Aβ40 ratio [Срок оценки: baseline up to estimated 12 months]
• Change from baseline on Preclinical Alzheimer Cognitive Composite (PACC) score [Срок оценки: baseline up to estimated 12 months]
• Change from baseline on XpressO MoCA [Срок оценки: baseline up to estimated 12 months]

Критерии участия

Критерии включения

• Without dementia as determined by: MoCA >21 or MMSE > 24 or Clinical Dementia Rating <1
• Minimum of 6 years of formal education
• Stable psychoactive medication for 1 month prior to screening with no intention to change dose during treatment period
• Capacity to provide written consent in English or French

Критерии исключения

• Clinical diagnosis of major neurocognitive disorder
• Unstable psychiatric condition:
• Clinically significant active suicidal ideations
• Unstable medical condition in the opinion of the investigator.
• Known or suspected history of drug or alcohol dependence or abuse within one year of the screening visit
• Currently taking a DORA
• Allergy or significant adverse reaction to DORA
• Use of benzodiazepines or z-drugs > 2 times per week in the last month.
• Use of major and moderate CYP3A4 inducers and inhibitors
• Use of strong central nervous system depressants, opioids, strong analgesics, antipsychotics, sedative antidepressants.
• Active use of cholinesterase inhibitors or memantine
• Women who are breast feeding or pregnant
• Severe obstructive sleep apnea (OSA)\*
• Clinically significant non-treated rapid eye movement (REM) sleep behavior disorder, restless leg syndrome or parasomnia;
• Diagnosis of narcolepsy

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Да

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Четверное слепое

Основная цель

Профилактика

Центры проведения

Канада · 1 центр

• Centre StoP-Alzheimer (Douglas Mental Health University Institute - Research Centre) — Montreal

Идентификаторы

NCT: NCT07213349 · DARAD2025 · BH-10983

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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