Purpose

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

Conditions

Eligibility

Eligible Ages
All ages
Eligible Genders
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.

Study Design

Phase
Phase 2
Study Type
Interventional
Allocation
Randomized
Intervention Model
Parallel Assignment
Primary Purpose
Treatment
Masking
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Arm Groups

ArmDescriptionAssigned Intervention
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 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.
  • 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 names:
    • Placebo

Recruiting Locations

University of Texas, Health Science Center San Antonio
San Antonio, Texas 78229
Contact:
rachel Mulavelil
210-450-8132
mulavelil@uthscsa.edu

More Details

Status
Recruiting
Sponsor
Alzheimer's Disease Cooperative Study (ADCS)

Study Contact

Genny Matthews
858-246-1318
brainlink@ucsd.edu

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).

Notice

Study information shown on this site is derived from ClinicalTrials.gov (a public registry operated by the National Institutes of Health). The listing of studies provided is not certain to be all studies for which you might be eligible. Furthermore, study eligibility requirements can be difficult to understand and may change over time, so it is wise to speak with your medical care provider and individual research study teams when making decisions related to participation.