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

• ClinicalTrials.gov Identifier: NCT03108846
• Recruitment Status: Recruiting
• First Posted: April 11, 2017
• Last Update Posted: May 7, 2021
• Sponsor: JHSPH Center for Clinical Trials
• Collaborator: National Institute on Aging (NIA)
• Information provided by (Responsible Party): Dave Shade, JHSPH Center for Clinical Trials

Tracking Information

• First Submitted Date: April 6, 2017
• First Posted Date: April 11, 2017
• Last Update Posted Date: May 7, 2021
• Actual Study Start Date: January 3, 2018
• Estimated Primary Completion Date: December 2021 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: December 11, 2017)

modified- Alzheimer's Disease Cooperative Study--Clinical Global Impression of Change (mADCS-CGIC) [ Time Frame: after 12 weeks ]

Clinical Global Impression of Change

Original Primary Outcome Measures (submitted: April 6, 2017)

mADCS-CGIC [ Time Frame: after 12 weeks ]

Clinical Global Impression of Change

• Current Secondary Outcome Measures: Not Provided
• Original Secondary Outcome Measures: Not Provided
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Escitalopram for Agitation in Alzheimer's Disease
• Official Title: Escitalopram for Agitation in Alzheimer's Disease
• 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 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. Following the 12-week study treatment period, participants will be followed for another 12 weeks without receiving study drug. Participants who do show a response to the psychosocial intervention will not be randomized to study drug but will be followed remotely for the 24-week follow-up period.
• Study Type: Interventional
• Study Phase: Phase 3

Study Design

Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description:

Over-encapsulation

Primary Purpose: Treatment

• Condition: Dementia

Intervention

• Drug: Escitalopram
  5-15 mg/day (target: 15mg/day if tolerated)
  Other Name: Lexapro
• Drug: Placebo
  Masked placebo
  Other Name: non-applicable

Study Arms

• Experimental: Escitalopram
  Escitalopram up to 15mg/day taken as 1-3 capsules each containing 5mg escitalopram once per day in the morning
  Intervention: Drug: Escitalopram
• Placebo Comparator: Placebo
  1-3 capsules each containing placebo only once per day in the morning
  Intervention: Drug: Placebo

• 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.

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: April 6, 2017): 392
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: August 2022
• Estimated Primary Completion Date: December 2021 (Final data collection date for primary outcome measure)

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 109 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Dave Shade, JD; 4109558175; dshade@jhmi.edu

Contact: Stephan Ehrhardt, MD; 4109558175; sehrhar6@jhu.edu

• Listed Location Countries: Canada, United States

Administrative Information

• NCT Number: NCT03108846
• Other Study ID Numbers: S-CitAD; R01AG052510 ( U.S. NIH Grant/Contract )
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• 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

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Dave Shade, JHSPH Center for Clinical Trials
• Original Responsible Party: Same as current
• Current Study Sponsor: JHSPH Center for Clinical Trials
• Original Study Sponsor: Same as current
• Collaborators: National Institute on Aging (NIA)

Investigators

• Study Chair: Constantine Lyketsos, MD, MHS; Johns Hopkins University

• PRS Account: JHSPH Center for Clinical Trials
• Verification Date: May 2021