Escitalopram for Agitation in Alzheimer's Disease

NCT03108846 | Active Not Recruiting Phase 3 DMC FDA Drug

• 2 other identifiers: S-CitADR01AG052510
• Study Type: interventional
• Target: 187
• Locations: 2 countries
• Sites: 29

Brief Summary

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

Conditions

Dementia

Keywords

Alzheimer's Disease; Agitation

Outcome Measures

Primary Outcomes (1)

• modified- Alzheimer's Disease Cooperative Study--Clinical Global Impression of Change (mADCS-CGIC)

  Clinical Global Impression of Change

  after 12 weeks

Study Arms (2)

Escitalopram

EXPERIMENTAL

Escitalopram up to 15mg/day taken as 1-3 capsules each containing 5mg escitalopram once per day in the morning

Drug: Escitalopram

Placebo

PLACEBO COMPARATOR

1-3 capsules each containing placebo only once per day in the morning

Drug: Placebo

Interventions

Escitalopram DRUG

5-15 mg/day (target: 15mg/day if tolerated)

Also known as: Lexapro

Escitalopram

Placebo DRUG

Masked placebo

Also known as: non-applicable

Placebo

Eligibility Criteria

• Age: 18 Years - 109 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Alzheimer's dementia diagnosed clinically by the National Institute on Aging (NIA) and the Alzheimer's Association (AA) (2011 NIA/AA criteria)
• Mini-Mental State Examination Telephone (MMSET) score of 3-20 inclusive
• Meets the International Psychogeriatric Association (IPA) provisional criteria for agitation in cognitive disorders
• 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'
• 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)
• 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
• Stable (for ≥ 7 days) dosing of antipsychotics for agitation or psychosis, if being used at all
• A medication for agitation is appropriate, in the opinion of the study physician

You may not qualify if:

• 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)
• 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)
• Residence in a skilled nursing or Long-Term Acute Care (LTAC) facility
• 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
• Prior failed treatment attempt with citalopram or escitalopram for agitation after adequate trial, at minimally accepted dose
• Indication for psychiatric hospitalization or acute suicidality, in the opinion of the study physician
• 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)
• 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)
• 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
• 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
• Recent (\< 14 days) changes in Dextromethorphan/quinidine, prazosin, and pimavanserin
• Recent (\< 14 days) use of medical marijuana

Sponsors & Collaborators

• JHSPH Center for Clinical Trials: lead
• National Institute on Aging (NIA): collaborator

Study Sites (29)

Banner Sun Health Research Institute

Sun City, Arizona, 85351, United States

Location

Biomedical Research Foundation

Little Rock, Arkansas, 72205, United States

Location

University of Arkansas for Medical Sciences

Little Rock, Arkansas, 72205, United States

Location

University of California Los Angeles/VA Greater Los Angeles Healthcare System

Los Angeles, California, 90073, United States

Location

University of Southern California Keck School of Medicine Memory and Aging Center

Los Angeles, California, 90089, United States

Location

Miami Jewish Health Systems

Miami, Florida, 33137, United States

Location

Kansas School of Medicine-Wichita Center for Clinical Research

Wichita, Kansas, 67214, United States

Location

Maryland VA Health Care System

Baltimore, Maryland, 21202, United States

Location

Johns Hopkins University School of Medicine, Bayview Medical Center

Baltimore, Maryland, 21224, United States

Location

Alzheimer Disease Center

Quincy, Massachusetts, 02169, United States

Location

Hackensack Meridian Health

Hackensack, New Jersey, 07601, United States

Location

Columbia University

New York, New York, 10032, United States

Location

University of Rochester Medical Center

Rochester, New York, 14620, United States

Location

Ohio State University

Columbus, Ohio, 43221, United States

Location

Abington Neurological Associates, Ltd

Abington, Pennsylvania, 19001, United States

Location

Alzheimer Disease Research Center; University of Pittsburgh

Pittsburgh, Pennsylvania, 15213, United States

Location

Roper St. Francis Healthcare

Charleston, South Carolina, 29401, United States

Location

Baylor AT&T Memory Center

Dallas, Texas, 75231, United States

Location

UT Health San Antonio

San Antonio, Texas, 78229, United States

Location

University of Virginia Adult Neurology

Charlottesville, Virginia, 22903, United States

Location

Eastern Virginia Medical School

Norfolk, Virginia, 23510, United States

Location

Northwest Clinical Research Center

Bellevue, Washington, 98007, United States

Location

University of Calgary and Foothills Medical Centre

Calgary, Alberta, Canada

Location

Lawson Health Research Institute/Parkwood Institute

London, Ontario, N6C 0A7, Canada

Location

Neuropsychopharmacology Research Group, Sunnybrook

Toronto, Ontario, M4N 3M5, Canada

Location

Unity Health

Toronto, Ontario, M5B 1W8, Canada

Location

Centre for Addiction and Mental Health

Toronto, Ontario, M6J1H4, Canada

Location

Centre for Memory and Aging

Toronto, Ontario, Canada

Location

Ontario Shores

Whitby, Ontario, L1N 5S9, Canada

Location

Related Publications (2)

• Rajji TK, Baksh SN, Shade DM, Ismail Z, Burhan AM, Okhravi HR, Padala PR, Rosenberg PB, Schneider LS, Porsteinsson AP, Lyketsos CG; S-CitAD Research Group. Escitalopram for agitation in Alzheimer's dementia: a randomized controlled phase 3 trial. Nat Med. 2025 May;31(5):1586-1591. doi: 10.1038/s41591-025-03569-y. Epub 2025 Mar 25.

  PMID: 40133524 DERIVED

• 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.

  PMID: 31587995 DERIVED

MeSH Terms

Conditions

Dementia; Alzheimer Disease; Psychomotor Agitation

Interventions

Escitalopram

Condition Hierarchy (Ancestors)

Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurocognitive Disorders; Mental Disorders; Tauopathies; Neurodegenerative Diseases; Dyskinesias; Neurologic Manifestations; Psychomotor Disorders; Neurobehavioral Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Aberrant Motor Behavior in Dementia; Behavioral Symptoms; Behavior

Intervention Hierarchy (Ancestors)

Propylamines; Amines; Organic Chemicals; Nitriles; Benzofurans; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Constantine Lyketsos, MD, MHS

  Johns Hopkins University

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Over-encapsulation
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director, S-CitAD Coordinating Center

Study Record Dates

• First Submitted: April 6, 2017
• First Posted: April 11, 2017
• Study Start: January 3, 2018
• Primary Completion: April 5, 2024
• Study Completion: May 1, 2025
• Last Updated: January 31, 2025

Record last verified: 2025-01

Data Sharing

• IPD Sharing: Will not share

Locations

CA (7); US (22)