Ruthirakuhan Myuri T, Herrmann Nathan, Gallagher Damien, Andreazza Ana C, Kiss Alexander, Verhoeff Nicolaas Paul L G, Black Sandra E, Lanctôt Krista L
Hurvitz Brain Sciences Program, Sunnybrook Research Institute, 2075 Bayview Avenue, M4N 3M5, Toronto, ON, Canada.
Department of Pharmacology, University of Toronto, 1 King's College Circle, M5S 3K1, Toronto, ON, Canada.
Contemp Clin Trials Commun. 2019 May 23;15:100385. doi: 10.1016/j.conctc.2019.100385. eCollection 2019 Sep.
Agitation is a prevalent and difficult-to-treat symptom in patients with moderate-to-severe Alzheimer's disease (AD). Though there are nonpharmacological and pharmacological interventions recommended for the treatment of agitation, the efficacy of these are modest and not always consistent. Furthermore, the safety profiles of currently prescribed medications are questionable. Nabilone, a synthetic cannabinoid, has a distinct pharmacological profile that may provide a safer and more effective treatment for agitation, while potentially having benefits for weight and pain. Additionally, emerging evidence suggests nabilone may have neuroprotective effects. We describe a clinical trial investigating the safety and efficacy of nabilone for the treatment of agitation in patients with moderate-to-severe AD. This will be a double-blind, randomized cross-over study comparing 6 weeks of nabilone (0.5-2 mg) and placebo, with a 1-week washout preceding each phase. Study outcomes will be measured at baseline and end of treatment for each treatment phase. The primary outcome measure will be agitation as assessed by the Cohen-Mansfield Agitation Inventory. The secondary outcomes include safety, behaviour (Neuropsychiatric Inventory), cognition (standardized Mini Mental Status Exam and either Severe Impairment Battery or Alzheimer's disease Assessment Scale-Cognitive subscale) and global impression (Clinician's Global Impression of Change). Exploratory outcomes include pain (Pain Assessment in Advanced AD), nutritional status (Mini-Nutritional Assessment-Short Form), caregiver distress (NPI caregiver distress), and blood-based biomarkers. A safe and efficacious pharmacological intervention for agitation, with effects on pain and weight loss in patients with moderate-to-severe AD could increase quality-of-life, reduce caregiver stress and avoid unnecessary institutionalization and related increases in health care costs.
NCT02351882.
激越在中重度阿尔茨海默病（AD）患者中是一种普遍且难以治疗的症状。尽管有非药物和药物干预措施被推荐用于治疗激越，但这些措施的疗效一般且并非总是一致。此外，当前所开药物的安全性也存在疑问。纳布隆，一种合成大麻素，具有独特的药理学特征，可能为激越提供更安全有效的治疗，同时可能对体重和疼痛有益。此外，新出现的证据表明纳布隆可能具有神经保护作用。我们描述了一项临床试验，研究纳布隆治疗中重度AD患者激越的安全性和有效性。这将是一项双盲、随机交叉研究，比较6周的纳布隆（0.5 - 2毫克）和安慰剂，每个阶段之前有1周的洗脱期。研究结果将在每个治疗阶段的基线和治疗结束时进行测量。主要结局指标将是通过科恩 - 曼斯菲尔德激越量表评估的激越情况。次要结局包括安全性、行为（神经精神科问卷）、认知（标准化简易精神状态检查以及严重损害成套测验或阿尔茨海默病评估量表 - 认知子量表）和整体印象（临床医生的总体变化印象）。探索性结局包括疼痛（晚期AD疼痛评估）、营养状况（微型营养评定 - 简表）、照料者困扰（神经精神科问卷照料者困扰）和血液生物标志物。一种对中重度AD患者激越安全有效的药物干预措施，对疼痛和体重减轻有作用，可能会提高生活质量、减轻照料者压力，并避免不必要的机构化以及相关医疗费用的增加。
NCT02351882
