Antipsychotic Discontinuation in Alzheimer's Disease
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 入组人数
- 180
- 试验地点
- 7
- 主要终点
- Relapse by Study Week 32
研究概览
简要总结
In patients with Alzheimer's disease (AD) who respond to antipsychotic treatment of psychosis and/or agitation/aggression, the relapse risk after discontinuation is not established. AD patients with psychosis and/or agitation/aggression receive 16 weeks of open risperidone treatment (Phase A). Responders are then randomized, double-blind, to one of three arms in Phase B: (1) continuation risperidone for 32 weeks, (2) risperidone for 16 weeks followed by placebo for 16 weeks, (3) placebo for 32 weeks. The primary outcome is time to relapse of psychosis/agitation.
详细描述
This multicenter study (6 academic sites and 2 non-academic sites) involves treating AD patients (assisted living or nursing home patients, and outpatients) using an atypical antipsychotic, risperidone. In Phase A, 180 AD patients with psychosis and/or agitation/aggression receive open treatment with risperidone for 16 weeks. Responders are randomized, double-blind, to one of three arms in Phase B: (1) continuation risperidone for the next 32 weeks, (2) risperidone for the next 16 weeks followed by placebo for 16 weeks, or (3) placebo for the next 32 weeks. The primary hypothesis is that in the first 16 weeks of Phase B, relapse risk will be lower with continuation risperidone (Arms 1 + 2) compared to discontinuation on placebo (Arm 3). The secondary hypothesis is that in the second 16 weeks of Phase B, relapse risk will be lower with continuation risperidone (Arm 1) compared to discontinuation on placebo (Arm 2). For both randomized time periods, the proportions who relapse will be compared for interpretive support. This design provides useful data on the efficacy and side effects of longer term treatment with risperidone, and, in particular, critical information about the time to relapse and likelihood of relapse in patients switched from risperidone to placebo. This information is essential to guide the clinician toward optimal use of such medications in one of the most challenging types of patients: the AD patient with psychosis and/or agitation/aggression. The results of this study will also help to address Federal regulations urging early antipsychotic discontinuation in nursing homes.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 50 Years 至 95 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Dementia, either sex, age 50-95 years
- •Probable Alzheimer's disease
- •Intellectual impairment present for at least 6 months
- •Mini Mental State Exam (MMSE) score of 5-26 for outpatients and 2-26 for nursing home patients
- •Availability of informant who has had direct contact with the patient for an average of at least once every week during the 3 months prior to study entry
- •Meets Neuropsychiatric Inventory (NPI) criteria for either (1) psychosis, or (2) agitation/aggression
- •Able to mobilize independently (if wheelchair-bound, the patient must be able to self-propel)
- •Free of psychotropic medication (or able to tolerate washout) for at least 1 week prior to study entry. Low dose antidepressants and sedative/hypnotics allowed if they cannot be washed out and the dose remains stable for the study duration
- •Expected to complete the study (including all efficacy evaluations) and be without major sensory impairment that would prevent participation in any aspect of the study
排除标准
- •Current primary Axis I psychiatric disorder other than AD
- •Substance abuse or dependence currently, or within the past year
- •Dementia due to head trauma
- •History of allergy to risperidone or intolerance to risperidone
- •Diffuse Lewy body disease
- •History of seizure disorder, infectious encephalitis, Parkinson's disease, central nervous system (CNS) neoplasm, tardive dyskinesia, stroke, transient ischemic attack (TIA) or uncontrolled atrial fibrillation
- •Use of monoamine oxidase inhibitors (MAOIs) and unable to undergo 3-week washout; patients also may not take MAOIs for 2 weeks after completing the study
- •In treatment with (a) depot antipsychotic within 2 weeks of the screening visit
- •Untreated or incompletely treated hypothyroidism
- •Active, unstable medical condition that requires active medication adjustment or surgery
- •Need for electroconvulsive treatment (ECT)
- •Significant risk for harm to themselves or others as a result of randomization to placebo
- •History of malignant neoplasm during the last 5 years
研究组 & 干预措施
Risperidone-risperidone
Risperidone for 16 weeks followed by risperidone for 16 weeks
干预措施: risperidone (Drug)
Risperidone-Placebo
Risperidone for 16 weeks followed by placebo for 16 weeks
干预措施: risperidone (Drug)
Placebo-Placebo
Placebo for 16 weeks followed by placebo for 16 weeks
干预措施: risperidone (Drug)
结局指标
主要结局
Relapse by Study Week 32
时间窗: 0-16 weeks in Phase B (16-32 weeks in study)
A relapse occurred in Phase B (post-randomization) if both of the following criteria were met: 1. Increase in the Neuropsychiatric Inventory (NPI) core score of 30% or more OR a 5-point increase from the baseline NPI score at the end of Phase A 2. A score of 6 (much worse) or 7 (very much worse) on the Clinical Global Impression-Change (CGI-C) at any visit.
次要结局
- Relapse by Study Week 48(16-32 weeks in Phase B (32-48 weeks in study))
- Mini Mental State Exam (MMSE)(Phase B, weeks 1-16 (study weeks 16-32))
- Treatment Emergent Symptoms Scale (TESS)(Phase B, weeks 1-16 (study weeks 16-32))
- Extrapyramidal Signs (EPS)(Phase B, weeks 1-16 (study weeks 16-32))
- AIMS(Phase B, weeks 1-16 (study weeks 16-32))
- Physical Self-Maintenance Scale (PSMS)(Phase B, weeks 1-16 (study weeks 16-32))
- Weight(Phase B, weeks 1-16 (study weeks 16-32))