Double Blind Clinical Trial of Daridorexant (Dual Orexin Receptor Antagonist) for Alzheimer Disease Prevention
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 240
- 试验地点
- 1
- 主要终点
- Change in plasma p-tau217/np-tau217 ratio
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
Research Staff (Research Assistants, Nurse, Coordinators)
入排标准
- 年龄范围
- 50 Years 至 90 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •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
排除标准
- •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
研究组 & 干预措施
Daridorexant 50 mg
干预措施: Daridorexant 50 mg (Drug)
Placebo
干预措施: Placebo (Drug)
结局指标
主要结局
Change in plasma p-tau217/np-tau217 ratio
时间窗: baseline up to estimated 12 months
Biological progression as measured by p-tau217/np-tau217 ratio in plasma
次要结局
- Change from baseline on XpressO MoCA(baseline up to estimated 12 months)
- Change in plasma p-tau181/np-tau181 ratio(baseline up to estimated 12 months)
- Change in plasma Aβ42/Aβ40 ratio(baseline up to estimated 12 months)
- Change from baseline on Preclinical Alzheimer Cognitive Composite (PACC) score(baseline up to estimated 12 months)
研究者
Sylvia Villeneuve
Director of the StoP-AD Centre
Douglas Mental Health University Institute