Pilot trial of dronabinol adjunctive treatment of agitation in Alzheimer's disease (AD)

屈大麻酚辅助治疗阿尔茨海默病 (AD) 躁动的初步试验

• 批准号: 9104639
• 负责人: Brent Peter Forester
• 金额: $ 102.47万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-09-01 至 2021-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9104639
• 关键词: Acquired Immunodeficiency Syndrome; Acute; Adult; Adverse event; Affect; Aggressive behavior; Aging; Agitation; Agonist; Alzheimer' s Disease; American; Anorexia; Anti-Anxiety Agents; Anti-Inflammatory Agents; Anti-inflammatory; Antidepressive Agents; Antipsychotic Agents; Area; Behavioral; Blinded; Body Weight decreased; CNR1 gene; Cannabis; Caregiver Burden; Caregivers; Caring; Case Series; Citalopram; Clinical; Cognition; Cognitive; Consensus; Controlled Study; Data; Data Analyses; Delirium; Dementia; Desire for food; Dose; Dose-Limiting; Double-Blind Method; Dronabinol; Emotional; Endocannabinoids; Equipment and supply inventories; FDA approved; Family; Formulation; Frail Elderly; Frontotemporal Dementia; Geriatric Psychiatry; Hospitals; Huntington Disease; Impaired cognition; Inpatients; International; Intervention; Intoxication; Label; Laboratory Study; Lead; Lorazepam; Marijuana; Marinol; Measures; Mental Depression; Methods; Motor; Multicenter Trials; Nausea; Netherlands; Neurodegenerative Disorders; Oral; Outcome; Parkinson Disease; Participant; Patients; Persons; Pharmaceutical Preparations; Pharmacology; Pharmacotherapy; Phase; Phase III Clinical Trials; Placebo Control; Placebos; Plants; Problem behavior; Public Health; Publishing; Randomized Clinical Trials; Reporting; Research; Risk; Role; Safety; Severities; Site; Sleep; Sleeplessness; Societies; Source; Stress; Sum; Symptoms; Testing; Tetrahydrocannabinol; Toxic effect; Treatment Efficacy; Vomiting; antidepressant effect; chemotherapy; clinical research site; comparative efficacy; confusion assessment method; disability; improved; innovation; mortality; neuropsychiatric disorder; neuropsychiatric symptom; neuropsychiatry; novel; older patient; pilot trial; primary outcome; psychosocial; public health relevance; receptor; secondary outcome; therapy development; vocalization; Acquired Immunodeficiency Syndrome; Acute; Adult; Adverse event; Affect; Aggressive behavior; Aging; Agitation; Agonist; Alzheimer' s Disease; American; Anorexia; Anti-Anxiety Agents; Anti-Inflammatory Agents; Anti-inflammatory; Antidepressive Agents; Antipsychotic Agents; Area; Behavioral; Blinded; Body Weight decreased; CNR1 gene; Cannabis; Caregiver Burden; Caregivers; Caring; Case Series; Citalopram; Clinical; Cognition; Cognitive; Consensus; Controlled Study; Data; Data Analyses; Delirium; Dementia; Desire for food; Dose; Dose-Limiting; Double-Blind Method; Dronabinol; Emotional; Endocannabinoids; Equipment and supply inventories; FDA approved; Family; Formulation; Frail Elderly; Frontotemporal Dementia; Geriatric Psychiatry; Hospitals; Huntington Disease; Impaired cognition; Inpatients; International; Intervention; Intoxication; Label; Laboratory Study; Lead; Lorazepam; Marijuana; Marinol; Measures; Mental Depression; Methods; Motor; Multicenter Trials; Nausea; Netherlands; Neurodegenerative Disorders; Oral; Outcome; Parkinson Disease; Participant; Patients; Persons; Pharmaceutical Preparations; Pharmacology; Pharmacotherapy; Phase; Phase III Clinical Trials; Placebo Control; Placebos; Plants; Problem behavior; Public Health; Publishing; Randomized Clinical Trials; Reporting; Research; Risk; Role; Safety; Severities; Site; Sleep; Sleeplessness; Societies; Source; Stress; Sum; Symptoms; Testing; Tetrahydrocannabinol; Toxic effect; Treatment Efficacy; Vomiting; antidepressant effect; chemotherapy; clinical research site; comparative efficacy; confusion assessment method; disability; improved; innovation; mortality; neuropsychiatric disorder; neuropsychiatric symptom; neuropsychiatry; novel; older patient; pilot trial; primary outcome; psychosocial; public health relevance; receptor; secondary outcome; therapy development; vocalization

 DESCRIPTION (provided by applicant): Background: Alzheimer's disease (AD) is the commonest neurodegenerative disease of aging affecting an estimated 5 million persons in the U.S. and anticipated to triple by 2030. The symptoms are not only cognitive but emotional, and neuropsychiatric symptoms such as agitation, depression, and apathy are highly prevalent in AD and a major cause of burden to patients, families, and society. Agitation in AD (Agit-AD) is a particularly acute cause of caregiver burden, and current treatments for Agit-AD are not highly effective particularly for severely impaired patients. Thus, there is a need for improved treatments for Agit-AD. Specific aim 1: To evaluate the efficacy of 3 weeks dronabinol vs. placebo adjunctive treatment in 80 inpatients with severe Agit-AD. Hypothesis 1: Compared to placebo, dronabinol treatment will be associated with a greater reduction in symptoms of agitation as measured by the PAS and the agitation domain of the Neuropsychiatric Inventory-Clinician Version (NPI-C). Specific Aim 2: To evaluate the safety profile of dronabinol vs. placebo adjunctive treatment in 80 inpatients with severe Agit-AD. Hypothesis 2: Dronabinol treatment will be well tolerated with no more than mild adverse events (AEs). Public Health Significance: There is a great need for better interventions that target Agit-AD, which is a major source of caregiver burden and stress, particularly for moderate to severe agitation. This could open the door to "repurposing" dronabinol as a novel and safe treatment for Agit-AD with significant public health impact. Innovation: 1) first North American RCT of dronabinol for Agit-AD; 2) first RCT of dronabinol at 10 mg dose. Current trials in the field limit the dose to 4-6 mg daily and underdosing should be assiduously avoided in an early phase trial to avoid missing potential benefit; 3) first multi-site RCT of dronabinol for Agit-AD. Method: We propose a three -week placebo-controlled, double-blind, randomized clinical trial of 10 mg daily dronabinol as an adjunct to currently used psychotropic medications in 80 inpatients with severe Agit-AD. The trial will be undertaken at two clinical research sites (Johns Hopkins and McLean Hospitals) and use the Pittsburgh Agitation Scale as primary outcome, with additional agitation scales (Cohen-Mansfield Agitation Inventory and Neuropsychiatry Inventory - Clinican Version), cognitive measures (MiniMental State Exam), and sleep and drug intoxication measures as secondary outcomes. Data analyses will be by intent-to-treat. Participants, clinical staff, and raters will b blinded to treatment assignment. Expected Results: if we observe benefit from dronabinol this could lead to a definitive hypothesis-testing phase 3 trial with potential impacts on public health If we observe no benefit at this relatively high dronabinol dose this will likely not lead to furthr development of this intervention. Impact on other research areas: agitation is common in other neuropsychiatric diseases and dronabinol might be helpful in those as well, including Parkinsons', Huntingtons', and frontotemporal dementia.

 描述（适用提供）：背景：阿尔茨海默氏病（AD）是影响美国估计有500万人的衰老的最常见的神经退行性疾病，预计到2030年将三倍。症状不仅是认知，而且是情感上的，而且是精神症状，以及神经精神病的症状，例如躁动，抑郁，抑郁症和公寓的患者和家庭中的一员，是一名劳动和家庭的一员。 AD（Agit-AD）的搅动是伯宁的特别急性原因，当前对Agit-AD治疗的治疗尤其对严重受损的患者特别有效。这是需要改善搅拌器的治疗方法。具体目的1：评估3周Dronabinol vs.安慰剂辅助治疗的有效性在80个严重的AD-AD的住院患者中。假设1：与安慰剂相比，Dronabinol治疗将与PAS和神经精神库存 - 临床 - 临床 - 临床 - 临床 - 临床 - 炎热症状（NPI-C）的搅动症状相关。具体目的2：评估Dronabinol与安慰剂辅助治疗的安全性，在80名严重搅拌器的住院患者中。假设2：Dronabinol处理将得到良好的耐受性，而无非是轻度不良事件（AES）。公共卫生的意义：迫切需要采取更好的干预措施，以抗击AD，这是护理人员燃烧和压力的主要来源，特别是对于中度至严重的躁动。这可能为“重新利用” Dronabinol作为对公共卫生影响重大影响的Agit-AD的一种新颖且安全的治疗打开大门。创新：1）Dronabinol的第一个北美RCT，用于Agit-AD； 2）Dronabinol的第一个RCT为10 mg剂量。现场试验的当前试验将剂量限制为每天4-6毫克，而服用不足应在早期试验中无助，以避免缺失潜在的收益； 3）Dronabinol的第一个多站点RCT用于Agit-AD。方法：我们提出了一项为期三周的安慰剂对照，双盲，随机临床试验，每天10 mg dronabinol作为当前在80种严重搅拌AD的住院患者中使用精神药物的辅助手段。该试验将在两个临床研究网站（Johns Hopkins和McLean Hospitals）进行，并将匹兹堡的搅动量表作为主要结果，并具有额外的搅动量表（Cohen -Mansfield搅动清单和神经精神病学库存 - 临床 - 临床 - 临床版本），认知能力测量结果（微型状态检查），并将其作为Seleperional Interimility Outsic Intex Interxication Intecary Incorpic Incoficess Incorpary Incomeds。数据分析将通过意图对待。参与者，临床人员和Rators将对治疗作业视而不见。预期结果：如果我们观察到Dronabinol受益于Dronabinol，这可能会导致确定的假设检验3期试验，如果我们在这种相对较高的Dronabinol剂量下没有受益的可能影响，那么对公共卫生的影响可能不会导致这种干预的进一步发展。对其他研究领域的影响：躁动在其他神经精神疾病中很常见，而Dronabinol也可能有助于其中包括帕金森氏症，亨廷顿顿氏症和额叶痴呆症。