Prazosin for Agitation in Alzheimer's Disease


Trial ID: NCT03710642


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

Official Title

Prazosin for Disruptive Agitation in Alzheimer's Disease (AD) (PEACE-AD)

Stanford Investigator(s)

Sharon Sha, MD, MS
Sharon Sha, MD, MS

Clinical Professor, Neurology & Neurological Sciences

Victor W. Henderson, MD, MS
Victor W. Henderson, MD, MS

Professor of Epidemiology and Population Health and of Neurology


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. 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

   4. Psychotropic medication, if used, should be stable for at least 2 weeks prior to

   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

15. P articipants whom the Site Principal Investigator deems to be otherwise unsuitable
   for participation.


drug: Prazosin

drug: Placebo oral capsule


Contact Information

Stanford University
School of Medicine
300 Pasteur Drive
Stanford, CA 94305