Division of Geriatric Psychiatry, New York State Psychiatric Institute, New York, USA; Department of Psychiatry, Columbia University Medical Center, New York, USA; Department of Neurology and Taub Institute for Research on Alzheimer's Disease and the Aging Brain, Columbia University Medical Center, New York, USA.
Division of Geriatric Psychiatry, New York State Psychiatric Institute, New York, USA.
Contemp Clin Trials. 2018 Aug;71:33-39. doi: 10.1016/j.cct.2018.05.019. Epub 2018 May 31.
Symptoms of agitation, aggression, and psychosis frequently occur in patients with Alzheimer's disease (AD). These symptoms are distressing to patients and caregivers, often lead to institutionalization, are associated with increased mortality, and are very difficult to treat. Lithium is an established treatment for bipolar and other psychotic disorders in which agitation can occur. The Lit-AD study is the first randomized, double-blind, placebo-controlled trial to assess the efficacy of lithium treatment for symptoms of agitation or aggression, with or without psychosis, in older adults diagnosed with AD. Patients are randomly assigned to low dose (150-600 mg) lithium or placebo, targeting a blood level of 0.2-0.6 mmol/L, stratified by the presence/absence of psychotic symptoms. The study duration for each patient is 12 weeks. The primary study outcome is change in the agitation/aggression domain score on the Neuropsychiatric Inventory (NPI) over the study period. The secondary outcome is improvement in neuropsychiatric symptoms defined as a 30% decrease in a NPI core score that combines agitation/aggression and psychosis domain scores. The Treatment Emergent Symptom Scale (TESS) is used to assess somatic side effects. Other exploratory analyses examine the associations between improvement on lithium and indices shown to be associated with response to lithium in bipolar disorder: serum brain-derived neurotrophic factor (BDNF) levels, a SNP in intron 1 of the ACCN1 gene, and variation at the 7q11.2 gene locus. If lithium demonstrates efficacy in this Phase II pilot trial, a Phase III study will be developed to establish its clinical utility in these patients.
ClinicalTrials.gov Identifier NCT02129348.
目的：评估在有或无精神病症状的阿尔茨海默病（AD）老年患者中，锂治疗激越或攻击症状（伴或不伴精神病）的疗效。
设计：这是一项多中心、随机、双盲、安慰剂对照试验，患者被随机分配至低剂量（150-600mg）锂或安慰剂组，目标血药浓度为 0.2-0.6mmol/L，按精神病症状的存在/不存在分层。每位患者的研究时间为 12 周。
主要结局：研究期间神经精神问卷（NPI）激越/攻击域评分的变化。
次要结局：神经精神症状的改善定义为 NPI 核心评分降低 30%，该评分综合了激越/攻击和精神病域评分。采用治疗时出现的症状量表（TESS）评估躯体副作用。其他探索性分析检查了锂治疗改善与以下指标之间的关联：血清脑源性神经营养因子（BDNF）水平、ACCn1 基因内含子 1 中的 SNP 以及 7q11.2 基因座的变异。如果锂在这项 II 期试验中显示出疗效，将开发 III 期研究以确定其在这些患者中的临床应用价值。
注册：ClinicalTrials.gov 标识符 NCT02129348。
