Working… Menu

Prazosin for Agitation in Alzheimer's Disease

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT03710642
Recruitment Status : Active, not recruiting
First Posted : October 18, 2018
Last Update Posted : October 7, 2021
National Institute on Aging (NIA)
VA Puget Sound Health Care System
Alzheimer's Association
Information provided by (Responsible Party):
Alzheimer's Disease Cooperative Study (ADCS)

Brief Summary:

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

Condition or disease Intervention/treatment Phase
Alzheimer's Disease Disruptive Behavior Drug: Prazosin Drug: Placebo oral capsule Phase 2

Detailed Description:

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 approximately 186 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).

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 186 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Prazosin for Disruptive Agitation in Alzheimer's Disease (AD) (PEACE-AD)
Actual Study Start Date : October 23, 2018
Estimated Primary Completion Date : December 31, 2021
Estimated Study Completion Date : February 28, 2022

Arm Intervention/treatment
Active Comparator: 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

  1. mg QAM and 2 mg QHS for days 8 to 10
  2. 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.

Drug: Prazosin
Oral prazosin HCl capsules (or placebo) will be administered twice daily, with individualized doses up to a maximum of 4 mg QAM mid-morning and 6 mg at bedtime (QHS), or matching placebo capsules
Other Names:
  • Prazosin HCl
  • Minipress

Placebo Comparator: Placebo oral capsule
Placebo medication will be administered in a titration schedule mimicking the active comparator treatment.
Drug: Placebo oral capsule
Placebo capsule matched to appearance of active drug.
Other Name: Placebo

Primary Outcome Measures :
  1. ADAS-Clinical Global Impression of Change in Agitation (CGIC) [ Time Frame: 12 weeks ]
    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 participant is rated on a 7-point Likert scale. Scores can range from 1 (improvement) to 7 (worsening).

Secondary Outcome Measures :
  1. Neuropsychiatric Inventory-Nursing Home version (NPI-NH) [ Time Frame: 12 weeks ]
  2. Neuropsychiatric Inventory (home based) (NPI) [ Time Frame: 12 weeks ]

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

Layout table for eligibility information
Ages Eligible for Study:   Child, Adult, Older Adult
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  1. Males and females with probable or possible AD by NINCDS-ADRDA criteria utilizing medical history; medical records review; and documented physical, neurological, and other examinations and laboratory tests. At Screening, physical, neurological and other examinations; and laboratory tests will be performed as possible and tolerated by the agitated participants. Brain imaging is not a requirement.
  2. Participants must reside in either a participating LTC or at home with full-time caregiving.
  3. Participants must have disruptive agitation significant enough to disrupt caregiving and, in the opinion of the Site Principal Investigator, to justify further treatment. Disruptive agitation, defined as having any combination of the following target behaviors, 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), must have occurred nearly daily during the previous week and at least intermittently for 4 weeks prior to screening, documented on the Behavioral Inclusion Criteria Checklist at Screening. Target behaviors may be any combination of the listed domains as long as they meet the above-described criteria for frequency and severity.
  4. Psychotropic medication, if used, should be stable for at least 2 weeks prior to randomization.
  5. If taking cholinesterase inhibitor and/or memantine, must be on stable dose(s) for 3 months prior to randomization.
  6. During the week before randomization, the above-described behaviors must be rated as of at least "moderate" severity. These behaviors must be problematic in that they cause participant and caregiver distress and/or interfere with essential care or disrupt their living environment.

Exclusion Criteria:

  1. 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).
  2. Other neurodegenerative diseases, including Parkinson's disease and Huntington's disease, or cerebral tumor.
  3. 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.
  4. Current treatment for seizure disorder. (Note: anticonvulsants prescribed for disruptive agitation are acceptable).
  5. Abnormal laboratory values with clinical significance in the opinion of the site Principal Investigator.
  6. 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.
  7. Bedbound; participants may be ambulatory or use a wheelchair.
  8. Absence of any comprehensible language.
  9. 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).
  10. Preexisting recurrent hypotension (systolic blood pressure [BP] <110).
  11. 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).
  12. 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.
  13. Women of childbearing potential (must be at least 2 years post-menopausal or surgically sterile for inclusion).
  14. 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.
  15. Participants whom the Site Principal Investigator deems to be otherwise unsuitable for participation.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT03710642

Layout table for location information
United States, Arizona
Banner Sun Health Research Institute
Sun City, Arizona, United States, 85351
United States, California
University of Southern California
Los Angeles, California, United States, 90033
University of California, San Diego (UCSD)
San Diego, California, United States, 92093
Alta California Medical Group
Simi Valley, California, United States, 93065
Stanford University
Stanford, California, United States, 94305
United States, Kentucky
University of Kentucky
Lexington, Kentucky, United States, 40506
United States, Maine
Northern Light/Acadia Hospital Eastern Maine Medical Center
Bangor, Maine, United States, 04401
United States, New York
VAMC: James J Peters
Bronx, New York, United States, 10468
SUNY Upstate Medical University
Syracuse, New York, United States, 13210
United States, Oregon
Oregon Health and Science University
Portland, Oregon, United States, 97239
United States, South Carolina
Roper St. Francis Hospital
Charleston, South Carolina, United States, 29401
United States, Texas
University of Texas, Health Science Center San Antonio
San Antonio, Texas, United States, 78229
United States, Washington
University of Washington
Seattle, Washington, United States, 98104-2499
University of Washington
Seattle, Washington, United States, 98108
Sponsors and Collaborators
Alzheimer's Disease Cooperative Study (ADCS)
National Institute on Aging (NIA)
VA Puget Sound Health Care System
Alzheimer's Association

Layout table for additonal information
Responsible Party: Alzheimer's Disease Cooperative Study (ADCS) Identifier: NCT03710642    
Other Study ID Numbers: ADC-042-PRAZ
5U19AG010483 ( U.S. NIH Grant/Contract )
First Posted: October 18, 2018    Key Record Dates
Last Update Posted: October 7, 2021
Last Verified: September 2021

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Alzheimer's Disease Cooperative Study (ADCS):
Additional relevant MeSH terms:
Layout table for MeSH terms
Alzheimer Disease
Psychomotor Agitation
Problem Behavior
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Neurodegenerative Diseases
Neurocognitive Disorders
Mental Disorders
Neurologic Manifestations
Psychomotor Disorders
Neurobehavioral Manifestations
Behavioral Symptoms
Antihypertensive Agents
Adrenergic alpha-1 Receptor Antagonists
Adrenergic alpha-Antagonists
Adrenergic Antagonists
Adrenergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs