Prazosin Treatment for Disruptive Agitation in Alzheimer's Disease

• ClinicalTrials.gov Identifier: NCT01126099
• Recruitment Status: Completed
• First Posted: May 19, 2010
• Results First Posted: May 21, 2015
• Last Update Posted: May 21, 2015
• Sponsor: Seattle Institute for Biomedical and Clinical Research
• Collaborators: National Institute on Aging (NIA); VA Puget Sound Health Care System
• Information provided by (Responsible Party): Seattle Institute for Biomedical and Clinical Research

Study Description

Brief Summary:

A study of outpatient participants with Alzheimer's disease or a related dementia who have difficult behaviors that are upsetting for them or their caregivers. Prazosin is a medication that is commonly used to treat people with high blood pressure. Research with prazosin has shown that it may be effective in treating behavioral problems by reducing excess adrenalin effects in the brain.

Condition or disease	Intervention/treatment	Phase
Alzheimer's Disease	Drug: Prazosin; Drug: Placebo	Not Applicable

Detailed Description:

This is a 24 week study with 14 visits to the research clinic. Approximately 6 of these visits may be done by phone. Additional phone checks are scheduled at the beginning of each 12 week part of the study. Participants will have a 50:50 chance of being on prazosin or placebo in the first 12 weeks of the study. For the second 12 weeks, all participants will take prazosin.

Study visits include a physical and neurological exam; memory testing; interviews with the caregiver about behaviors; and vital signs.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 20 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Prazosin Treatment for Disruptive Agitation in Alzheimer's Disease
• Study Start Date: March 2010
• Actual Primary Completion Date: March 2014
• Actual Study Completion Date: March 2014

Arms and Interventions

Arm	Intervention/treatment
Experimental: Prazosin; In the double blind phase (12 weeks), study participants will take either prazosin for placebo. For the open label phase (12 weeks), all study participants will take prazosin.	Drug: Prazosin; 4 mg capsules twice daily for 12 weeks; Other Name: minipress
Placebo Comparator: Placebo; In the double blind phase (12 weeks), study participants will take either prazosin for placebo. For the open label phase (12 weeks), all study participants will take prazosin.	Drug: Placebo; Placebo capsules twice daily for 12 weeks; Other Name: inert substance

Outcome Measures

Primary Outcome Measures :

1. Alzheimer's Disease Cooperative Study - Clinical Global Impression of Change [ Time Frame: 12 Weeks after Baseline ]
   This scale represents the raters overall impression of improvement or worsening, and is assessed at the last visit. 1 = Marked improvement, 1 = Moderate improvement, 3 = Minimal improvement, 4 = No change, 5 = Minimal worsening, 6 = Moderate worsening, 7 = Marked worsening.
2. Change in Neuropsychiatric Inventory Score [ Time Frame: 12 weeks ]
   Neuropsychiatric Inventory score change from Baseline to last observation.The Neuropsychiatric Inventory is a scale that quantifies behavioral and psychiatric symptoms in patients with dementia. The scale ranges from 0 to 144, with 0 being no symptoms.

Secondary Outcome Measures :

1. Change in Brief Psychiatric Rating Scale Total Score [ Time Frame: 12 Weeks after Baseline ]
   Brief Psychiatric Rating Scale score change from Baseline to last observation. The Brief Psychiatric Rating Scale measures 18 psychiatric symptom domains. The scale ranges from 18 to 126, where 18 indicates no psychiatric symptoms.
2. Days in Study [ Time Frame: 12 weeks after Baseline ]
   The number of days participants remained in the study during the Double Blind Phase. Please note that although the length of follow-up designated in the protocol was 12 weeks, a number of participants were in this phase longer (e.g. the dose titration phase took longer than 3 weeks, assessments were delayed due to scheduling conflicts, etc.) Therefore the length of time in the Double Blind Phase can exceed 12 weeks (84 days).

Eligibility Criteria

• Ages Eligible for Study: Child, Adult, Older Adult
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• No age limit
• Probable or Possible Alzheimer's Disease
• Disruptive agitated behaviors at least twice a week (overly anxious or excited, making offensive comments.....)
• Stable medications for 2 weeks
• Must have a caregiver who spends 10 hours per week caring for the participant and agrees to participate in all evaluation sessions

Exclusion Criteria:

• Cardiovascular: unstable angina, recent myocardial infarction, preexisting hypotension (systolic BP less than 110) or orthostatic hypotension (≥20 mmHg drop in systolic BP following 2 minutes of standing posture)
• Any unstable medical condition
• Exclusionary medications: current treatment with prazosin, other alpha-1 blockers (trazodone, sildenafil, vardenafil or tadalafil)
• Psychoactive medications: subjects may be psychoactive medication-free or be partial responders (by subjective assessment of referring health care professional) to one psychoactive medication from any of the following classes: antipsychotics, anticonvulsants, mood stabilizers, antidepressants, benzodiazepines, or buspirone. Partial response is defined as some improvement in agitated behavior but persistence of agitated behaviors severe enough to cause patient distress and/or difficulty with caregiving. Although not formally rated, this improvement is equivalent to a Clinical Global Impression of Change rating of no more than minimal improvement (improvement is noticed by not enough to improve patient function or caregiver's practical management of the patient).
• Psychiatric/behavioral: lifetime schizophrenia; current delirium, mania, depression, or uncontrolled persistent distressing psychotic symptoms (hallucinations, delusions), substance abuse, panic disorder, or any behavior which poses an immediate danger to patient or others or which results in the patient being too uncooperative to meet the requirements of study participation.

Contacts and Locations

Locations

United States, Washington

Veterans Affairs Puget Sound Health Care System

Seattle, Washington, United States, 98108

Sponsors and Collaborators

Seattle Institute for Biomedical and Clinical Research

National Institute on Aging (NIA)

VA Puget Sound Health Care System

Investigators

• Principal Investigator: Elaine R Peskind, MD; University of Washington, VA Puget Sound Health Care System

More Information

• Responsible Party: Seattle Institute for Biomedical and Clinical Research
• ClinicalTrials.gov Identifier: NCT01126099
• Other Study ID Numbers: 1R01AG033133-01A1 ( U.S. NIH Grant/Contract ); 5R01AG033133 ( U.S. NIH Grant/Contract )
• First Posted: May 19, 2010
• Results First Posted: May 21, 2015
• Last Update Posted: May 21, 2015
• Last Verified: May 2015

Keywords provided by Seattle Institute for Biomedical and Clinical Research:

double-blind; treatment; prazosin; Disruptive behaviors in Alzheimer's Disease

Additional relevant MeSH terms:

Alzheimer Disease; Dementia; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Tauopathies; Neurodegenerative Diseases; Neurocognitive Disorders; Mental Disorders; Prazosin; 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