DIADS-3: An RCT of venlafaxine for depression in AD

DIADS-3：文拉法辛治疗 AD 抑郁症的随机对照试验

基本信息

批准号：
8530135
负责人：
PAUL B ROSENBERG
金额：
$ 52.28万
依托单位：
JOHNS HOPKINS UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2011
资助国家：
美国
起止时间：
2011-09-30 至 2016-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8530135
关键词：
Adverse event Affect Alzheimer&apos s Disease Antidepressive Agents Brain Caregivers Caring Clinical Cognitive Data Data Analyses Dementia Depressed mood Development Disease remission Distress Dose Double-Blind Method Effexor Elderly Emotional Failure Family Caregiver Funding Health Intervention Knowledge Lead Light Measures Mental Depression Methods Mirtazapine Mood Disorders Moods Neurodegenerative Disorders Norepinephrine Outcome Participant Patients Performance Persons Pharmaceutical Preparations Phase Placebo Control Placebos Publishing Quality of life Randomized Randomized Controlled Trials Recruitment Activity Reporting Research Infrastructure Research Personnel Safety Sampling Selective Serotonin Reuptake Inhibitor Serious Adverse Event Serotonin Sertraline Serum Site Societies Symptoms Testing United Kingdom United States National Institutes of Health Universities alternative treatment base cooperative study disability double-blind placebo controlled trial effective therapy experience impression improved inhibitor/antagonist neuropsychiatry noradrenergic primary outcome psychosocial response reuptake secondary outcome single episode major depressive disorder venlafaxine

项目摘要

DESCRIPTION (provided by applicant): DIADS-3: A randomized double-blind, placebo-controlled trial of venlafaxine for depression in Alzheimer's Disease Alzheimer's disease (AD) is a growing health problem currently affecting 5.3 million persons in the U.S., a number that is estimated to triple by 2050. Neuropsychiatric symptoms are near-universal in AD and are a major contributor to patient and caregiver distress. One of the most prominent and distressing neuropsychiatric symptoms is depression, affecting up to 50% of patients with AD. There is currently no pharmacologic or non-pharmacologic intervention proven to be effective in depression of AD (dAD), and we have recently published results from a hypothesis-testing randomized controlled trial (RCT) of sertraline for dAD which showed no drug effect. Thus, there is a great need for development of new treatments for dAD. Most of the prior trials have studied serotonin-selective reuptake inhibitors, but there is considerable for the involvement of noradrenaline (NA) as well as serotonin (5-HT) in brain mechanisms underlying depression and AD. Thus, serotonin-noradrenaline reuptake inhibitors (SNRIs) are attractive alternatives for treatment of dAD. To date there are no SNRI RCTs in dAD with adequate dosing for SNRI effect and adequate duration to detect lasting changes in mood outcomes; the one RCT of venlafaxine is underdosed (at a dose with only SSRI effect) and too brief to adequately assess mood outcomes (6 weeks). Thus, we propose DIADS-3: a proof-of-concept RCT of venlafaxine for dAD. 64 participants with dAD will be randomized to Effexor XR (target dose of 225 mg daily) vs. placebo for 12 weeks' double-blind randomized treatment. The trial will be conducted at Johns Hopkins University by a highly experienced AD trials team that has recruited >800 participants for trials since 2004. Primary outcomes at 12 weeks are 1) rates of response on the modified AD Cooperative Study-Clinical Global Impression of Change (mADCS-CGIC); 2) rates of remission defined as a Cornell Scale for Depression in Dementia (CSDD) score d6 PLUS a mADCS-CGIC d2; 3) CSDD scores on CSDD. Secondary outcomes will include safety assessments and examination of the association of serum venlaxine + metabolite levels with response. Data analyses will be on an intent-to-treat basis, and multiple imputation will be utilized as appropriate for missing data. DIADS-3 has the potential to significantly impact on treatment of dAD and, if drug effect is observed, to lead to a definitive hypothesis- testing trial of venlafaxine for dAD.

DESCRIPTION (provided by applicant): DIADS-3: A randomized double-blind, placebo-controlled trial of venlafaxine for depression in Alzheimer's Disease Alzheimer's disease (AD) is a growing health problem currently affecting 5.3 million persons in the U.S., a number that is estimated to triple by 2050. Neuropsychiatric symptoms are near-universal in AD and are a major contributor to patient and caregiver distress.最突出和令人痛苦的神经精神症状之一是抑郁症，影响多达50％的AD患者。目前尚无证明有效的AD（DAD）抑郁症的药理学或非药物干预措施，并且我们最近从Sertraline的假设检测随机对照试验（RCT）发表了结果，但没有显示出药物作用。因此，迫切需要为爸爸开发新疗法。大多数先前的试验都研究了5-羟色胺选择性再摄取抑制剂，但是有相当大的参与去甲肾上腺素（NA）以及5-羟色胺（5-HT）参与抑郁症和AD的脑机制。因此，5-羟色胺 - 甲肾上腺素再摄取抑制剂（SNRIS）是治疗爸爸的有吸引力的替代方法。迄今为止，爸爸没有SNRI RCT，具有足够的剂量来用于SNRI效应，并且有足够的持续时间来检测情绪结果的持续变化；静脉f夫辛的一个RCT被剂量不足（只有SSRI效应的剂量），太短了，无法充分评估情绪结局（6周）。因此，我们提出Diads-3：爸爸的Venlafaxine的概念验证RCT。有64名爸爸的参与者将被随机分配给EffExor XR（每天的目标剂量为225 mg），而安慰剂则为12周的双盲随机治疗。该试验将由经验丰富的广告试验团队在约翰·霍普金斯大学（Johns Hopkins University）进行，该小组自2004年以来一直招募了> 800名参与者进行试验。主要结果为12周，是1）修改后的AD合作研究 - 统一统计全球变化印象（MADCS-CGIC）的响应率； 2）缓解速率定义为痴呆症（CSDD）得分D6加上MADCS-CGIC D2的康奈尔量表； 3）CSDD上的CSDD分数。次要结果将包括安全评估和检查血清Venlaxine +代谢物水平与反应的关联。数据分析将以对治疗的意图为基础，并且将使用多个插补来丢失数据。 DIADS-3有可能对爸爸的治疗产生重大影响，如果观察到药物作用，则会导致Venlafaxine对DAD进行确定的假设检测试验。