Prazosin for Agitation in Alzheimer's Disease
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
- Alzheimer's Disease
- Disruptive Behavior
- Eligible Ages
- All ages
- Eligible Genders
- Accepts Healthy Volunteers
- Males and females with probable or possible AD by NINCDS-ADRDA criteria utilizing medical history; medical records review; physical, neurological, and psychiatric exam; and screening laboratory tests, who are residing in a LTC facility. Brain imaging is not a requirement.
- At Baseline (BL), participants must have disruptive agitation (documented on the Behavioral Inclusion Criteria Checklist and detailed on the ADCS-CGIC-A BL Worksheet) defined as having at least one of the following target behaviors with > moderately severe rating at least 5 times per week for a minimum duration of 4 weeks: a) irritability, b) physically and/or verbally aggressive behavior, c) physically resistive to necessary care, and/or d) 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 the LTC environment. Target behaviors may be any combination of the listed domains, as long as there are 5 or more instances per week of at least moderate severity.
- 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(s) for 3 months prior to randomization.
- Must be able to swallow capsules whole.
- 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 Parkinson's disease and Huntington's 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.
- 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 Investigator's 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 to 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 blood pressure [BP] <110).
- Preexisting orthostatic hypotension (>20 mmHg drop in systolic BP following 2 minutes of standing posture [or sitting if unable to stand], 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, avanafil, and trazodone.
- Women of childbearing potential (must be at least 2 years post-menopausal or surgically sterile for inclusion).
- The participant may not be an immediate family member of personnel directly affiliated with this study, the study site or study funding agency. Immediate family member is defined as a spouse, parent, child, or sibling, any of whom may be related by blood, adoption, or marriage.
- Participants whom the Site Principal Investigator deems to be otherwise unsuitable for participation.
- Phase 2
- Study Type
- Intervention Model
- Parallel Assignment
- Primary Purpose
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
|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.||
Placebo oral capsule
|Placebo medication will be administered in a titration schedule mimicking the active comparator treatment.||
- Alzheimer's Disease Cooperative Study (ADCS)
Study ContactGenny Matthews
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 defined as having at least one of any of the following target behaviors with ≥ moderately severe rating at least 5 times per week for a minimum of 4 weeks: 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) in approximately 186 Alzheimer's disease (AD) residents in long-term care (LTC) settings. LTC is defined as assisted living or skilled nursing facility. 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).