Prazosin for Agitation in Alzheimer's Disease
Condition: Alzheimer's Disease; Disruptive Behavior
MeSH terms: Alzheimer Disease; Psychomotor Agitation; Problem Behavior
Intervention: Prazosin; Placebo oral capsule
Intervention description: 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 capsule matched to appearance of active drug.
Intervention MeSH terms: Prazosin
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 35.0
Sex: All
Healthy volunteers: No
Keywords: Dementia; Agitation; PEACE-AD

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
    

Eligibility criteria:

        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
                  Checklist.

          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.