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Alzheimer's DiseasePhase 2NCT03710642

Prazosin for Agitation in Alzheimer's Disease

A Phase 2 study testing Prazosin in people with Alzheimer's Disease and Disruptive Behavior, run by Alzheimer's Disease Cooperative Study (ADCS) at 14 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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 Read more about this study

Who is it for?
Any age
Conditions the study is for
Alzheimer's Disease, Disruptive Behavior
What is being tested?
Prazosin
Type of treatment
Pill or oral medicine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
35 participants
Where
14 sitesUnited States
Study dates
23 Oct 2018to 5 Jan 2022
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages Any age
  • All sexes
  • No healthy volunteers
  • Child, Adult, Older adult

Who may be able to join

  • Participants must meet all of the following criteria be included in the study:
  • 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.
  • Participants must either reside in an LTC that is associated with the study site or at home with full-time caregiving.
  • 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:
  • irritability,
  • physically and/or verbally aggressive behavior,
Show all 11Show fewer
  • physical resistiveness to necessary care
  • 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.
  • Psychotropic medication, if used, should be stable for at least 2 weeks prior to randomization.
  • If taking cholinesterase inhibitor and/or memantine, must be on stable dose for 3 months prior t o randomization.
  • During the week before randomization, the above-described behaviors of eligible participants must be rated as of at least moderate severity.

Who cannot join

  • Participants meeting any of the following criteria must not be included in the study:
  • 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).
  • Other neurodegenerative diseases, including Parkinsons disease and Huntingtons disease, or cerebral tumor.
  • 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.
  • Current treatment for seizure disorder (Note: anticonvulsants prescribed for disruptive agitation in the absence of seizure disorder will be allowed).
  • Abnormal laboratory values with clinical significance in the opinion of the site Principal Investigator.
Show all 24Show fewer
  • 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.
  • Bedbound; participants may be ambulatory or use a wheelchair.
  • Absence of any comprehensible language.
  • 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).
  • 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.
  • 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).
  • 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.
  • 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
  • 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.
  • P articipants whom the Site Principal Investigator deems to be otherwise unsuitable for participation.

Trial locations and contacts

14 sites in 1 country.

14 sites in 1 country

United States14 sites
  • Northern Light/Acadia Hospital Eastern Maine Medical Center

    Bangor, Maine, 04401

  • Roper St. Francis Hospital

    Charleston, South Carolina, 29401

  • University of Kentucky

    Lexington, Kentucky, 40506

  • University of Southern California

    Los Angeles, California, 90033

  • Oregon Health and Science University

    Portland, Oregon, 97239

  • University of Texas, Health Science Center San Antonio

    San Antonio, Texas, 78229

  • University of California, San Diego (UCSD)

    San Diego, California, 92093

  • University of Washington

    Seattle, Washington, 98104-2499

  • University of Washington

    Seattle, Washington, 98108

  • Alta California Medical Group

    Simi Valley, California, 93065

  • Stanford University

    Stanford, California, 94305

  • Banner Sun Health Research Institute

    Sun City, Arizona, 85351

  • SUNY Upstate Medical University

    Syracuse, New York, 13210

  • VAMC: James J Peters

    The Bronx, New York, 10468

Other trials in United States

About this study

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

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

Read the 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 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).

Being tested
Prazosin, Placebo oral capsule
Keywords
Dementia, Agitation, PEACE-AD
Medical subject headings
Alzheimer Disease, Problem Behavior, Dementia, Psychomotor Agitation

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • PrazosinDrug

    Also called Prazosin HCl, Minipress

    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 capsuleDrug

    Also called Placebo

    Placebo capsule matched to appearance of active drug.

Study groups in NCT03710642
Study groupRoleWhat they receive
Treatment (Prazosin)Active comparatorEligible 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.
Receives: Drug: Prazosin
Placebo oral capsulePlacebo comparatorPlacebo medication will be administered in a titration schedule mimicking the active comparator treatment.
Receives: Drug: Placebo oral capsule

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. ADCS-Clinical Global Impression of Change in Agitation (ADCS-CGIC-A)

    The ADCS-CGIC-A is the primary outcome measure. It will be anchored to disruptive agitation, the target behaviors in this study. It measures whether the effects of active treatment are substantial enough to be detected by a skilled and experienced clinician on the basis of a direct examination of the participant and an interview of the participant's primary caregiver and other LTC facility staff. The baseline assessment is qualitative therefore there is no score at baseline; post-baseline scores represent a change score compared to baseline.

    The ADCS-CGIC-A is a 7-point scale that is structured as the clinician's assessment of change from baseline compared to the ADCS-CGIC-A Baseline Worksheet. There is no baseline score; post-baseline scores range from 1 (improvement) to 7 (worsening). A score of 1-2 indicates clinically meaningful improvement; a score of 3-5 indicates no clinically meaningful change; a score of 6-7 indicates clinically meaningful worsening.

    Measured: From Baseline through Week 12.

Secondary outcomes (6)
  1. Neuropsychiatric Inventory (NPI)/Neuropsychiatry Inventory-Nursing Home Version (NPI-NH)

    The NPI was designed to characterize the neuropsychiatric symptoms and psychopathology of patients with AD and other dementias residing in the community about which information was obtained from family caregivers. The content of the questions and their scoring in the NPI-NH are identical to those of the NPI except for some slight rephrasing to be consistent with the LTC environment where information is gathered from professional caregivers. Assessment of the impact of behavioral disturbances on family and professional caregivers, is assessed by a caregiver distress scale in the NPI and an occupational disruptiveness scale in the NPI-NH; scoring of this component remains identical. Minimum score is 0 and highest score is 144. A higher score means a worse outcome.

    This outcome is the change from baseline to week 12.

    Measured: 12 weeks

  2. Rescue Medication: Total mg Lorazepam Administered

    Cumulative total dose of Lorazepam rescue medication administered during the trial. Information on the total mg rescue lorazepam administered will be collected as additional secondary outcome measures. If prazosin is more effective than placebo, it is predicted that participants randomized to prazosin will be prescribed lower cumulative mg of rescue lorazepam for management of persistent or worsening disruptive agitation.

    Measured: 12 weeks

  3. Study Discontinuations

    Cox proportional hazard modelling comparing the median time to drop out between treatment groups.

    Measured: 12 weeks

  4. Responder Analysis on CGIC-A

    Comparison of proportions of responders versus non responders on the ADCS-CGIC-A. Responders are defined as those with moderate or marked improvement in agitation symptoms compared to baseline assessment.

    Measured: 12 weeks

  5. ADCS-ADL-Severe

    The ADCS-ADL-Severe questionnaire is a secondary outcome measure aimed at detecting functional decline in people with severe AD. This scale is best suited for evaluating people with MMSE scores below 15/30, or equivalent. Questions are administered to a qualified caregiver informant about a set of 19 basic and instrumental ADL. Instrumental ADL are selected to be relevant to this level of severity of dementia, e.g., obtaining a beverage, turning lights on and off, turning a faucet on and off. Performance of each of these activities during the past 4 weeks, as well as the level of performance, are rated. A total score is derived by summing scores across items, and ranges from 0 (maximal impairment) to 54 (maximally independent function).

    This outcome is the change from baseline to week 12.

    Measured: 12 weeks

  6. Caregiver Distress on NPI/NPI-NH

    Comparison of effects on caregiver distress/occupational disruptiveness scores on the NPI/NPI-NH. Minimum score is 0 and maximum score is 60. A higher score is a worse outcome.

    This outcome is the change from baseline to week 12.

    Measured: 12 weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted18 Oct 2018
  2. Study start23 Oct 2018
  3. Primary completion5 Jan 2022
  4. Study completion5 Jan 2022

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
35 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03710642
Sponsor's protocol ID
ADC-042-PRAZ
Other IDs
5U19AG010483
Status last verified
Jan 2023
First submitted
9 Oct 2018
Last updated
6 Feb 2023
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: Data sharing is integral to the ADCS's mission to develop and execute innovative clinical trials focused on interventions that may prevent, delay, or treat the expression of Alzheimer's disease and related dementias. The ADCS is committed to sharing resources and tools, including data, biospecimens, trial designs, outcome and analysis measures following NIH guidelines. DATA SHARING: The ADCS Data and Sample Sharing Committee (DSSC) grants access to de-identified data to individuals who complete the request process and agree to the conditions in an ADCS/UCSD Data Use Agreement (DUA). After approval and receipt of the fully executed DUA, applicants are authorized to acquire data. Non-compliance with the DUA, including the requirement to provide requested updates will jeopardize further access to data.

Publications

  • 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.

    PubMed 7654129
  • 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.

    PubMed 3399726
  • 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.

    PubMed 8988954
  • 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.

    PubMed 10494443
  • 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.

    PubMed 17069768
  • 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.

    PubMed 23846759

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Prazosin in people with Alzheimer's Disease and Disruptive Behavior, run by Alzheimer's Disease Cooperative Study (ADCS) at 14 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 11 inclusion and 24 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 6 Feb 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 14 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 6 Feb 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

ADCS-Clinical Global Impression of Change in Agitation (ADCS-CGIC-A) (time frame: From Baseline through Week 12.). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03710642, which also lists 6 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Feb 2023.

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