Prazosin for Agitation in Alzheimer's Disease

NCT ID: NCT03710642

Last Updated: 2023-02-06

Study Results

Results available

Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.

View full results

Basic Information

Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.

Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

35 participants

Study Classification

INTERVENTIONAL

Study Start Date

2018-10-23

Study Completion Date

2022-01-05

Brief Summary

Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.

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

Detailed Description

Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.

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).

Conditions

See the medical conditions and disease areas that this research is targeting or investigating.

Alzheimer's Disease Disruptive Behavior

Study Design

Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.

Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

Review each arm or cohort in the study, along with the interventions and objectives associated with them.

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.

Group Type ACTIVE_COMPARATOR

Prazosin

Intervention Type DRUG

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

Placebo oral capsule

Placebo medication will be administered in a titration schedule mimicking the active comparator treatment.

Group Type PLACEBO_COMPARATOR

Placebo oral capsule

Intervention Type DRUG

Placebo capsule matched to appearance of active drug.

Interventions

Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.

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

Intervention Type DRUG

Placebo oral capsule

Placebo capsule matched to appearance of active drug.

Intervention Type DRUG

Other Intervention Names

Discover alternative or legacy names that may be used to describe the listed interventions across different sources.

Prazosin HCl Minipress Placebo

Eligibility Criteria

Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.

Inclusion Criteria

Participants must meet all of the following criteria be included in the study:

1. 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.
2. Participants must either reside in an LTC that is associated with the study site 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 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:

1. irritability,
2. physically and/or verbally aggressive behavior,
3. physical resistiveness to necessary care
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 for 3 months prior t o randomization.
6. During the week before randomization, the above-described behaviors of eligible participants must be rated as of at least moderate severity.

Exclusion Criteria

Participants meeting any of the following criteria must not be included in the study:

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 Parkinsons disease and Huntingtons 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 in the absence of seizure disorder will be allowed).
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 Investigators 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 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).
10. 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 \<110. For inclusion, new systolic measurement following medication adjustment must be ≥110.
* 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 ≥110.
* Any systolic reading \<100 is exclusionary.
11. 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).
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 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
14. 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.
15. P articipants whom the Site Principal Investigator deems to be otherwise unsuitable for participation.
Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

Meet the organizations funding or collaborating on the study and learn about their roles.

National Institute on Aging (NIA)

NIH

Sponsor Role collaborator

VA Puget Sound Health Care System

FED

Sponsor Role collaborator

Alzheimer's Association

OTHER

Sponsor Role collaborator

Alzheimer's Disease Cooperative Study (ADCS)

OTHER

Sponsor Role lead

Responsible Party

Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.

Responsibility Role SPONSOR

Principal Investigators

Learn about the lead researchers overseeing the trial and their institutional affiliations.

Howard Feldman

Role: PRINCIPAL_INVESTIGATOR

Alzheimer's Disease Cooperative Study (ADCS)

Locations

Explore where the study is taking place and check the recruitment status at each participating site.

Banner Sun Health Research Institute

Sun City, Arizona, United States

Site Status

University of Southern California

Los Angeles, California, United States

Site Status

University of California, San Diego (UCSD)

San Diego, California, United States

Site Status

Alta California Medical Group

Simi Valley, California, United States

Site Status

Stanford University

Stanford, California, United States

Site Status

University of Kentucky

Lexington, Kentucky, United States

Site Status

Northern Light/Acadia Hospital Eastern Maine Medical Center

Bangor, Maine, United States

Site Status

SUNY Upstate Medical University

Syracuse, New York, United States

Site Status

VAMC: James J Peters

The Bronx, New York, United States

Site Status

Oregon Health and Science University

Portland, Oregon, United States

Site Status

Roper St. Francis Hospital

Charleston, South Carolina, United States

Site Status

University of Texas, Health Science Center San Antonio

San Antonio, Texas, United States

Site Status

University of Washington

Seattle, Washington, United States

Site Status

University of Washington

Seattle, Washington, United States

Site Status

Countries

Review the countries where the study has at least one active or historical site.

United States

References

Explore related publications, articles, or registry entries linked to this study.

Peskind ER, Wingerson D, Murray S, Pascualy M, Dobie DJ, Le Corre P, Le Verge R, Veith RC, Raskind MA. Effects of Alzheimer's disease and normal aging on cerebrospinal fluid norepinephrine responses to yohimbine and clonidine. Arch Gen Psychiatry. 1995 Sep;52(9):774-82. doi: 10.1001/archpsyc.1995.03950210068012.

Reference Type BACKGROUND
PMID: 7654129 (View on PubMed)

Torroba Alvarez L, Hermida Donate JM, Ezpeleta Baquedano C, Munoz Zato E. [Methemoglobinemia secondary to the treatment of opportunistic infections in patients with AIDS]. Rev Clin Esp. 1988 Mar;182(5):289-90. No abstract available. Spanish.

Reference Type BACKGROUND
PMID: 3399726 (View on PubMed)

Elrod R, Peskind ER, DiGiacomo L, Brodkin KI, Veith RC, Raskind MA. Effects of Alzheimer's disease severity on cerebrospinal fluid norepinephrine concentration. Am J Psychiatry. 1997 Jan;154(1):25-30. doi: 10.1176/ajp.154.1.25.

Reference Type BACKGROUND
PMID: 8988954 (View on PubMed)

Raskind MA, Peskind ER, Holmes C, Goldstein DS. Patterns of cerebrospinal fluid catechols support increased central noradrenergic responsiveness in aging and Alzheimer's disease. Biol Psychiatry. 1999 Sep 15;46(6):756-65. doi: 10.1016/s0006-3223(99)00008-6.

Reference Type BACKGROUND
PMID: 10494443 (View on PubMed)

Raskind MA, Peskind ER, Hoff DJ, Hart KL, Holmes HA, Warren D, Shofer J, O'Connell J, Taylor F, Gross C, Rohde K, McFall ME. A parallel group placebo controlled study of prazosin for trauma nightmares and sleep disturbance in combat veterans with post-traumatic stress disorder. Biol Psychiatry. 2007 Apr 15;61(8):928-34. doi: 10.1016/j.biopsych.2006.06.032. Epub 2006 Oct 25.

Reference Type BACKGROUND
PMID: 17069768 (View on PubMed)

Raskind MA, Peterson K, Williams T, Hoff DJ, Hart K, Holmes H, Homas D, Hill J, Daniels C, Calohan J, Millard SP, Rohde K, O'Connell J, Pritzl D, Feiszli K, Petrie EC, Gross C, Mayer CL, Freed MC, Engel C, Peskind ER. A trial of prazosin for combat trauma PTSD with nightmares in active-duty soldiers returned from Iraq and Afghanistan. Am J Psychiatry. 2013 Sep;170(9):1003-10. doi: 10.1176/appi.ajp.2013.12081133.

Reference Type BACKGROUND
PMID: 23846759 (View on PubMed)

Provided Documents

Download supplemental materials such as informed consent forms, study protocols, or participant manuals.

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Document Type: Informed Consent Form

View Document

Other Identifiers

Review additional registry numbers or institutional identifiers associated with this trial.

5U19AG010483

Identifier Type: NIH

Identifier Source: secondary_id

View Link

ADC-042-PRAZ

Identifier Type: -

Identifier Source: org_study_id

More Related Trials

Additional clinical trials that may be relevant based on similarity analysis.

Memantine for Agitation in Dementia
NCT00371059 COMPLETED PHASE4