Clinical trial NCT03108846: Escitalopram for Agitation in Alzheimer's Disease
Official title: Escitalopram for Agitation in Alzheimer's Disease
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: Dementia
Keywords: Alzheimer's Disease
Agitation
Lead sponsor: JHSPH Center for Clinical Trials
Sponsor class: OTHER
Collaborators: name: National Institute on Aging (NIA)
First posted: 2017-04-11
Enrollment: 187
Sex: ALL
Minimum age (years): 18
Maximum age (years): 109
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to evaluate the safety and efficacy of escitalopram for agitation in Alzheimer's dementia.

Detailed description: This study is designed to examine the efficacy and safety of escitalopram as treatment for agitation in Alzheimer's dementia (AD) patients. Participants with clinically significant agitation, and their caregiver(s), will receive a structured psychosocial intervention. Participants not showing a response three weeks later will be randomized 1:1 to escitalopram (up to 15 mg/day) or a matching placebo. Participants will receive study drug or placebo for 12 weeks, with in-person and remote (phone/video) visits at weeks 3, 6, 9, and 12, and with telephone contacts between in-person and remote visits. Participants who do show a response to the psychosocial intervention will not be randomized to study drug but will be followed remotely.

Eligibility criteria: Inclusion criteria

1. Alzheimer's dementia diagnosed clinically by the National Institute on Aging (NIA) and the Alzheimer's Association (AA) (2011 NIA/AA criteria)
2. Mini-Mental State Examination Telephone (MMSET) score of 3-20 inclusive
3. Meets the International Psychogeriatric Association (IPA) provisional criteria for agitation in cognitive disorders
4. Clinically significant agitation/aggression as assessed by the Neuropsychiatric Inventory (NPI) for which either:

   * The frequency is 'Very frequently,' or
   * The frequency is 'Frequently' AND the severity is 'Moderate' or 'Marked'
5. Provision of informed consent for participation in the study by both caregiver and participant (or, if participant is unable to provide informed consent, with surrogate consent and participant assent)
6. Availability of a caregiver who spends at least several hours per week with the participant, supervises his/her care, is willing to accompany the participant to study visits, and is willing to participate in the study
7. Stable (for ≥ 7 days) dosing of antipsychotics for agitation or psychosis, if being used at all
8. A medication for agitation is appropriate, in the opinion of the study physician

Exclusion criteria

1. Has major depression, as indicated by major depressive episode (MDE) in the past 90 days (meeting the Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-V) criteria)
2. Presence of another brain disease that fully explains the dementia, (e.g., extensive brain vascular disease, Parkinson's disease, dementia with Lewy bodies, traumatic brain injury, or multiple sclerosis)
3. Residence in a skilled nursing or Long-Term Acute Care (LTAC) facility
4. Contraindication to treatment with escitalopram as determined by a study physician, such as recent (30 days) use of monoamine oxidase inhibitors (MAOIs) or potential participant is hypersensitive to escitalopram or citalopram or any inactive ingredients
5. Prior failed treatment attempt with citalopram or escitalopram for agitation after adequate trial, at minimally accepted dose
6. Indication for psychiatric hospitalization or acute suicidality, in the opinion of the study physician
7. Recent (\< 7 days) changes in antipsychotics, anticonvulsants, or psychosis (delusions or hallucinations) requiring a new or change in antipsychotic treatment (in the opinion of the study physician)
8. Abnormal corrected QT interval using Bazett's formula (QTcB)\*\* as determined on enrollment ECG (defined as \> 450 ms for men and \> 470 ms for women)
9. Recent (30 days) presence of severely reduced renal function (as identified by a Glomerular filtration rate (GFR) clearance \< 30 mL/min) or reduced hepatic function
10. Current treatment (within 7 days) with any of the following:

    * antidepressants (other than trazodone, ≤ 100 mg per day at bedtime)
    * benzodiazepines (other than lorazepam), or
    * psychostimulants
11. Recent (\< 14 days) changes in Dextromethorphan/quinidine, prazosin, and pimavanserin
12. Recent (\< 14 days) use of medical marijuana
13. Current participation in a clinical trial or in any study that may add a significant burden or affect neuropsychological or other study outcomes
14. Significant communicative impairments that would affect participation in a clinical trial
15. Any condition that, in the opinion of the study physician, makes it medically inappropriate or risky for the potential participant to enroll in the trial

    * if the QTcB is determined while the rhythm is paced, 50 ms is subtracted from the calculated value. The study cardiologist must confirm eligibility in this scenario.

Primary outcomes:
measure: modified- Alzheimer's Disease Cooperative Study--Clinical Global Impression of Change (mADCS-CGIC)
timeFrame: after 12 weeks
Secondary outcomes:
Other outcomes:
Locations:
city: Sun City
country: United States
facility: Banner Sun Health Research Institute
state: Arizona
city: Little Rock
country: United States
facility: Biomedical Research Foundation
state: Arkansas
city: Little Rock
country: United States
facility: University of Arkansas for Medical Sciences
state: Arkansas
city: Los Angeles
country: United States
facility: University of California Los Angeles/VA Greater Los Angeles Healthcare System
state: California
city: Los Angeles
country: United States
facility: University of Southern California Keck School of Medicine Memory and Aging Center
state: California
city: Miami
country: United States
facility: Miami Jewish Health Systems
state: Florida
city: Wichita
country: United States
facility: Kansas School of Medicine-Wichita Center for Clinical Research
state: Kansas
city: Baltimore
country: United States
facility: Maryland VA Health Care System
state: Maryland
city: Baltimore
country: United States
facility: Johns Hopkins University School of Medicine, Bayview Medical Center
state: Maryland
city: Quincy
country: United States
facility: Alzheimer Disease Center
state: Massachusetts
city: Hackensack
country: United States
facility: Hackensack Meridian Health
state: New Jersey
city: New York
country: United States
facility: Columbia University
state: New York
city: Rochester
country: United States
facility: University of Rochester Medical Center
state: New York
city: Columbus
country: United States
facility: Ohio State University
state: Ohio
city: Abington
country: United States
facility: Abington Neurological Associates, Ltd
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Alzheimer Disease Research Center; University of Pittsburgh
state: Pennsylvania
city: Charleston
country: United States
facility: Roper St. Francis Healthcare
state: South Carolina
city: Dallas
country: United States
facility: Baylor AT&T Memory Center
state: Texas
city: San Antonio
country: United States
facility: UT Health San Antonio
state: Texas
city: Charlottesville
country: United States
facility: University of Virginia Adult Neurology
state: Virginia
city: Norfolk
country: United States
facility: Eastern Virginia Medical School
state: Virginia
city: Bellevue
country: United States
facility: Northwest Clinical Research Center
state: Washington
city: Calgary
country: Canada
facility: University of Calgary and Foothills Medical Centre
state: Alberta
city: London
country: Canada
facility: Lawson Health Research Institute/Parkwood Institute
state: Ontario
city: Toronto
country: Canada
facility: Neuropsychopharmacology Research Group, Sunnybrook
state: Ontario
city: Toronto
country: Canada
facility: Unity Health
state: Ontario
city: Toronto
country: Canada
facility: Centre for Addiction and Mental Health
state: Ontario
city: Toronto
country: Canada
facility: Centre for Memory and Aging
state: Ontario
city: Whitby
country: Canada
facility: Ontario Shores
state: Ontario
Study officials:
affiliation: Johns Hopkins University
name: Constantine Lyketsos, MD, MHS
role: STUDY_CHAIR
References:
citation: Ehrhardt S, Porsteinsson AP, Munro CA, Rosenberg PB, Pollock BG, Devanand DP, Mintzer J, Rajji TK, Ismail Z, Schneider LS, Baksh SN, Drye LT, Avramopoulos D, Shade DM, Lyketsos CG; S-CitAD Research Group. Escitalopram for agitation in Alzheimer's disease (S-CitAD): Methods and design of an investigator-initiated, randomized, controlled, multicenter clinical trial. Alzheimers Dement. 2019 Nov;15(11):1427-1436. doi: 10.1016/j.jalz.2019.06.4946. Epub 2019 Oct 3.