Prazosin for Disruptive Agitation in Alzheimer's Disease (AD) (PEACE-AD)
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 35
- 试验地点
- 13
- 主要终点
- ADCS-Clinical Global Impression of Change in Agitation (ADCS-CGIC-A)
研究概览
简要总结
The study evaluates the effects of Prazosin on agitation in adults with Alzheimer's disease.
Two thirds of the participants will participate in the medication portion, while one third will participate in the placebo portion
详细描述
Prazosin for Disruptive Agitation in Alzheimer's Disease (PEACE-AD) is a Phase IIb multicenter, randomized, double-blind, placebo-controlled trial of 12-weeks treatment with the brain active alpha-1 adrenoreceptor (AR) antagonist prazosin for disruptive agitation in 35 Alzheimer's disease (AD) residents in a long-term care (LTC) setting or living at home with full-time caregiving.
Distruptive agitation defined as having one or more of the following behaviors nearly daily during the previous week and at least intermittently for four weeks prior to screening: a) irritability, b) physically and/or verbally aggressive behavior, c) physically resistive to necessary care, d) and/or pressured motor activity (e.g., pressured pacing).
LTC is defined as assisted living or skilled nursing facility. Home dwelling participants require full-time caregiving defined as having continuous daily caregiving and a Study Partner who will assist in providing protocol specific information to the study team.
A previous single site pilot study addressing disruptive agitation in 22 predominantly LTC-residing AD participants demonstrated efficacy of prazosin on all three primary outcome measures.1 The current multicenter study is funded by the National Institute on Aging (NIA), and coordinated through the NIA-funded Alzheimer's Disease Cooperative Study (ADCS).
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
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Participants must meet all of the following criteria be included in the study:
- •Men and women with probable or possible AD by NINCDS-ADRDA criteria utilizing history; medical records review; physical and neurological exam; and laboratory tests (as applicable). Brain neuroimaging is not a requirement.
- •Participants must either reside in an LTC that is associated with the study site or at home with full-time caregiving.
- •Participants must have disruptive agitation significant enough to disrupt caregiving and, in the opinion of the Site Principal Investigator, to justify treatment. Disruptive agitation, defined as having any combination of the following target behaviors, must have occurred nearly daily during the previous week and at least intermittently for 4 weeks prior to screening:
- •irritability,
- •physically and/or verbally aggressive behavior,
- •physical resistiveness to necessary care
- •pressured motor activity (e.g., pressured pacing) These behaviors must be problematic in that they cause participant and caregiver distress and/or interfere with essential care or disrupt their living environment. Target behaviors may be any combination of the listed domains. Disruptive agitation must meet this threshold at Screening, documented on the Behavioral Inclusion Criteria Checklist.
- •Psychotropic medication, if used, should be stable for at least 2 weeks prior to randomization.
- •If taking cholinesterase inhibitor and/or memantine, must be on stable dose for 3 months prior t o randomization.
- •During the week before randomization, the above-described behaviors of eligible participants must be rated as of at least moderate severity.
排除标准
- •Participants meeting any of the following criteria must not be included in the study:
- •History of schizophrenia, schizoaffective disorder, or bipolar disorder according to the criteria of the most current version of the Diagnostic and Statistical Manual of Mental Disorders (DSM).
- •Other neurodegenerative diseases, including Parkinsons disease and Huntingtons disease, or cerebral tumor.
- •Dementia other than probable or possible AD per NINCDS-ADRDA criteria, such as human immunodeficiency virus (HIV) dementia, Creutzfeldt-Jakob disease, frontotemporal dementia, multiple cerebral infarctions, or normal pressure hydrocephalus.
- •Current treatment for seizure disorder (Note: anticonvulsants prescribed for disruptive agitation in the absence of seizure disorder will be allowed).
- •Abnormal laboratory values with clinical significance in the opinion of the site Principal Investigator.
- •Current unstable medical illness including delirium, worsening congestive heart failure, unstable angina, recent myocardial infarction (within the past 3 months), acute infectious disease, severe renal or hepatic failure, severe respiratory disease, metastatic cancer, or other conditions that, in the Site Principal Investigators opinion, could interfere with the analyses of safety and efficacy in this study.
- •Bedbound; participants may be ambulatory or use a wheelchair.
- •Absence of any comprehensible language.
- •Participation in another clinical trial for an investigational agent and took at least one dose of study drug (unless unblinded on placebo) within 12 weeks prior to screening. (The end of a previous investigational trial is defined as the date of the last dose of an investigational agent).
- •Preexisting recurrent hypotension (systolic BP <110).
- •If a reading of <110 systolic is measured at screening,
- •If the individual is taking antihypertensive medication: The Site PI should reassess the need for such medication and consider medication adjustments in consultation with the participants physician. One week following adjustment of antihypertensive(s), screening BP will be repeated for reassessment of eligibility. Further adjustment of antihypertensive medication regimen by the participants health care prescriber, may be indicated if systolic pressure remains <
- •For inclusion, new systolic measurement following medication adjustment must be ≥
- •If the individual is not taking antihypertensive medication: repeat at least 3 BP measures over the course of 7-14 days. For inclusion, all three follow-up systolic measurements must be ≥
- •Any systolic reading <100 is exclusionary.
- •Preexisting orthostatic hypotension (>20 mmHg drop in systolic BP following 2 minutes of standing posture [or sitting if unable to stand] and accompanied by dizziness, lightheadedness, or syncope).
- •A 2-week washout is required prior to BL for the following exclusionary medications: prazosin or other alpha-1 blocker, sildenafil, vardenafil, tadalafil, and avanafil.
- •Women of childbearing potential are not included in this study. Women of non-childbearing potential are defined as any of the following:
- •have been postmenopausal (no menstrual cycle for past 24 months)
- •do not have a uterus,
- •have bilateral tubal ligation,
- •have undergone bilateral salpingectomy, and/or bilateral oophorectomy
- •The participant may not be an immediate family member of personnel directly affiliated with this study, the study site or funding agency. Immediate family is defined as a spouse, parent, child, or sibling, any of whom may be related by blood, adoption, or marriage.
- •P articipants whom the Site Principal Investigator deems to be otherwise unsuitable for participation.
研究组 & 干预措施
Treatment (Prazosin)
Eligible participants will be randomized using a 2:1 schedule to prazosin or placebo and stratified by site and gender, and will follow a fixed titration scheme for the first 15 days, followed by a flexible does titration from days 15-29, then a maintenance phase stable dose from days 29 to the end of the 12 weeks study period.
Prazosin Fixed titration dose schedule for Days 1 to 14 1 mg QHS for Days 1 to 3
1 mg QAM and 1 mg QHS for days 4 to 7
- mg QAM and 2 mg QHS for days 8 to 10
- mg QAM and 2 mg QHS for days 11 to 14
Prazosin Flexible titration dose schedule for Days 15 to 29. 3 mg QAM and 3 mg QHS on day 15, 4 mg QAM and 4 mg QHS on day 22, 4 mg QAH and 6 mg QHS on day 29,
Dose increases will be allowed only during the fixed and flexible dosing periods.
干预措施: Prazosin (Drug)
Placebo oral capsule
Placebo medication will be administered in a titration schedule mimicking the active comparator treatment.
干预措施: Placebo oral capsule (Drug)
结局指标
主要结局
ADCS-Clinical Global Impression of Change in Agitation (ADCS-CGIC-A)
时间窗: From Baseline through Week 12.
The ADCS-CGIC-A is the primary outcome measure. It will be anchored to disruptive agitation, the target behaviors in this study. It measures whether the effects of active treatment are substantial enough to be detected by a skilled and experienced clinician on the basis of a direct examination of the participant and an interview of the participant's primary caregiver and other LTC facility staff. The baseline assessment is qualitative therefore there is no score at baseline; post-baseline scores represent a change score compared to baseline. The ADCS-CGIC-A is a 7-point scale that is structured as the clinician's assessment of change from baseline compared to the ADCS-CGIC-A Baseline Worksheet. There is no baseline score; post-baseline scores range from 1 (improvement) to 7 (worsening). A score of 1-2 indicates clinically meaningful improvement; a score of 3-5 indicates no clinically meaningful change; a score of 6-7 indicates clinically meaningful worsening.
次要结局
- Rescue Medication: Total mg Lorazepam Administered(12 weeks)
- Neuropsychiatric Inventory (NPI)/Neuropsychiatry Inventory-Nursing Home Version (NPI-NH)(12 weeks)
- Study Discontinuations(12 weeks)
- Responder Analysis on CGIC-A(12 weeks)
- ADCS-ADL-Severe(12 weeks)
- Caregiver Distress on NPI/NPI-NH(12 weeks)