Escitalopram for Agitation in Alzheimer's Disease (S-CitAD)

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

Study Overview

• Status: Active, not recruiting
• Conditions: Dementia
• Intervention / Treatment: Drug: Escitalopram; Drug: Placebo

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.

• Study Type: Interventional
• Enrollment (Actual): 187
• Phase: Phase 3

Contacts and Locations

Study Locations

• Canada
  • Alberta
    • Calgary, Alberta, Canada
      • University of Calgary and Foothills Medical Centre
  • Ontario
    • London, Ontario, Canada, N6C 0A7
      • Lawson Health Research Institute/Parkwood Institute
    • Toronto, Ontario, Canada, M6J1H4
      • Centre for Addiction and Mental Health
    • Toronto, Ontario, Canada, M5B 1W8
      • Unity Health
    • Toronto, Ontario, Canada, M4N 3M5
      • Neuropsychopharmacology Research Group, Sunnybrook
    • Toronto, Ontario, Canada
      • Centre for Memory and Aging
    • Whitby, Ontario, Canada, L1N 5S9
      • Ontario Shores
• United States
  • Arizona
    • Sun City, Arizona, United States, 85351
      • Banner Sun Health Research Institute
  • Arkansas
    • Little Rock, Arkansas, United States, 72205
      • University of Arkansas for Medical Sciences
    • Little Rock, Arkansas, United States, 72205
      • Biomedical Research Foundation
  • California
    • Los Angeles, California, United States, 90089
      • University of Southern California Keck School of Medicine Memory and Aging Center
    • Los Angeles, California, United States, 90073
      • University of California Los Angeles/VA Greater Los Angeles Healthcare System
  • Florida
    • Miami, Florida, United States, 33137
      • Miami Jewish Health Systems
  • Kansas
    • Wichita, Kansas, United States, 67214
      • Kansas School of Medicine-Wichita Center for Clinical Research
  • Maryland
    • Baltimore, Maryland, United States, 21202
      • Maryland VA Health Care System
    • Baltimore, Maryland, United States, 21224
      • Johns Hopkins University School of Medicine, Bayview Medical Center
  • Massachusetts
    • Quincy, Massachusetts, United States, 02169
      • Alzheimer Disease Center
  • New Jersey
    • Hackensack, New Jersey, United States, 07601
      • Hackensack Meridian Health
  • New York
    • New York, New York, United States, 10032
      • Columbia University
    • Rochester, New York, United States, 14620
      • University of Rochester Medical Center
  • Ohio
    • Columbus, Ohio, United States, 43221
      • Ohio State University
  • Pennsylvania
    • Abington, Pennsylvania, United States, 19001
      • Abington Neurological Associates, LTD
    • Pittsburgh, Pennsylvania, United States, 15213
      • Alzheimer Disease Research Center; University of Pittsburgh
  • South Carolina
    • Charleston, South Carolina, United States, 29401
      • Roper St. Francis Healthcare
  • Texas
    • Dallas, Texas, United States, 75231
      • Baylor AT&T Memory Center
    • San Antonio, Texas, United States, 78229
      • UT Health San Antonio
  • Virginia
    • Charlottesville, Virginia, United States, 22903
      • University of Virginia Adult Neurology
    • Norfolk, Virginia, United States, 23510
      • Eastern Virginia Medical School
  • Washington
    • Bellevue, Washington, United States, 98007
      • Northwest Clinical Research Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 105 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Escitalopram; Escitalopram up to 15mg/day taken as 1-3 capsules each containing 5mg escitalopram once per day in the morning	Drug: Escitalopram; 5-15 mg/day (target: 15mg/day if tolerated); Other Names: Lexapro
Placebo Comparator: Placebo; 1-3 capsules each containing placebo only once per day in the morning	Drug: Placebo; Masked placebo; Other Names: non-applicable

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
modified- Alzheimer's Disease Cooperative Study--Clinical Global Impression of Change (mADCS-CGIC)	Clinical Global Impression of Change	after 12 weeks

Collaborators and Investigators

• Sponsor: JHSPH Center for Clinical Trials
• Collaborators: National Institute on Aging (NIA)
• Investigators: Study Chair: Constantine Lyketsos, MD, MHS, Johns Hopkins University

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (Actual): January 3, 2018
• Primary Completion (Actual): April 5, 2024
• Study Completion (Estimated): May 1, 2025

Study Registration Dates

• First Submitted: April 6, 2017
• First Submitted That Met QC Criteria: April 6, 2017
• First Posted (Actual): April 11, 2017

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: January 30, 2025
• Last Verified: January 1, 2025

More Information

Terms related to this study

• Keywords: Alzheimer's Disease; Agitation
• Additional Relevant MeSH Terms: Aberrant Motor Behavior in Dementia; Neurologic Manifestations; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Mental Disorders; Behavioral Symptoms; Neurobehavioral Manifestations; Neurocognitive Disorders; Dementia; Tauopathies; Neurodegenerative Diseases; Dyskinesias; Psychomotor Disorders; Alzheimer Disease; Psychomotor Agitation; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Neurotransmitter Agents; Membrane Transport Modulators; Neurotransmitter Uptake Inhibitors; Serotonin Agents; Selective Serotonin Reuptake Inhibitors; Escitalopram
• Other Study ID Numbers: S-CitAD; R01AG052510 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes