Citalopram for Agitation in Alzheimer's Disease

Alzheimer's Disease Clinical Trial

— CitAD  

Official title:

A Multi-Center Randomized Placebo-Controlled Clinical Trial Study of Citalopram for the Treatment of Agitation in Alzheimer's Disease

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00898807
• Other study ID #: IA0155
• Secondary ID: R01AG031348
• Status: Completed
• Phase: Phase 3
• First received: May 11, 2009
• Last updated: June 26, 2014
• Start date: July 2009
• Est. completion date: September 2013

Study information

• Verified date: June 2014
• Source: JHSPH Center for Clinical Trials
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial Summary

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

Description:

This study is designed to examine the efficacy and safety of citalopram as treatment for clinically significant agitation in Alzheimer's dementia (AD) patients. It will also investigate pharmacogenomic, genetic, and clinical predictors of response to citalopram therapy. The management of agitation is a major priority in treating patients with AD. Non-pharmacologic options have limited effectiveness. Several pharmacologic options have been explored, but findings for anticonvulsants, antipsychotics, and cholinesterase inhibitors are disappointing or associated with questionable risk-benefit ratio. Better pharmacologic options are needed. Selective serotonin reuptake inhibitors (SSRIs) show promise as a treatment for agitation in AD, based on evidence of a link between agitation and brain serotonin system abnormalities in AD patients, and on preliminary clinical data from a single-site, randomized controlled trial (RCT) in which citalopram was superior to perphenazine and placebo.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 186
• Est. completion date: September 2013
• Est. primary completion date: September 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: N/A and older

Eligibility

Inclusion criteria

• Probable Alzheimer's disease (National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer's Disease and Related Disorders Association criteria), with Mini-Mental score of 5-28 inclusive

• A medication for agitation is appropriate, in the opinion of the study physician

• Clinically significant agitation for which either

1. the frequency of agitation as assessed by the Neuropsychiatric Inventory (NPI) is 'Very frequently', or

2. the frequency of agitation as assessed by the NPI is 'Frequently' AND the severity of the agitation as assessed by the NPI is 'Moderate', or 'Marked'

• Provision of informed consent for participation in the study by patient or surrogate (if necessary) and caregiver

• Availability of primary caregiver, who spends several hours a week with the patient and supervises his/her care, to accompany the patient to study visits and to participate in the study

• No change to Alzheimer's disease (AD) medications within the month preceding randomization, including starting, stopping, or dosage modifications

Exclusion criteria

• Meets criteria for Major Depressive Episode by Diagnostic and Statistical Manual of Mental Disorders, 4th edition, text revision (DSM-IV (TR)) criteria

• Presence of a brain disease that might otherwise explain the presence of dementia, such as extensive brain vascular disease, Parkinson's disease, dementia with Lewy bodies, traumatic brain injury, or multiple sclerosis

• Psychosis (delusions or hallucinations) requiring antipsychotic treatment in the opinion of the study physician

• Prolonged measure of the time between the start of the Q wave and the end of the T wave in the heart's electrical cycle (QT interval)

• Treatment with citalopram is contraindicated in the opinion of the study physician

• Failure of past treatment with citalopram for agitation after adequate trial at a minimally accepted dose (greater than or equal to 20 mg/day)

• Treatment with a medication that would prohibit the safe concurrent use of citalopram, such as Monoamine oxidases (MAO) inhibitors

• Need for psychiatric hospitalization or suicidal

• Current participation in a clinical trial or in any study that may add a significant burden or affect neuropsychological or other study outcomes

• Current treatment with antipsychotics, anticonvulsants (other than dilantin), other antidepressants (other than trazodone, less than or equal to 50 mg per day at bedtime), benzodiazepines (other than lorazepam), or psychostimulants

• Any condition that, in the opinion of the study physician, makes it medically inappropriate or risky for the patient to enroll in the trial

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Agitation
• Alzheimer Disease
• Alzheimer's Disease
• Psychomotor Agitation

Intervention

Drug:
• citalopram
target dose 30mg daily for 9 weeks
• placebo
daily for 9 weeks

Locations

Country	Name	City	State
Canada	Centre for Addiction and Mental Health	Toronto	Ontario
United States	Johns Hopkins University	Baltimore	Maryland
United States	Medical University of South Carolina Alzheimer's Research and Clinical Programs	Charleston	South Carolina
United States	University of Southern California Keck School of Medicine Memory and Aging Center	Los Angeles	California
United States	Columbia University	New York	New York
United States	VA Palo Alto Health Care System	Palo Alto	California
United States	University of Pennsylvania, Section of Geriatric Psychiatry, Ralston House	Philadelphia	Pennsylvania
United States	Monroe Community Hospital	Rochester	New York

Sponsors (3)

Lead Sponsor	Collaborator
JHSPH Center for Clinical Trials	National Institute of Mental Health (NIMH), National Institute on Aging (NIA)

Countries where clinical trial is conducted

United States,  Canada, 

References & Publications (2)

Drye LT, Ismail Z, Porsteinsson AP, Rosenberg PB, Weintraub D, Marano C, Pelton G, Frangakis C, Rabins PV, Munro CA, Meinert CL, Devanand DP, Yesavage J, Mintzer JE, Schneider LS, Pollock BG, Lyketsos CG; CitAD Research Group. Citalopram for agitation in Alzheimer's disease: design and methods. Alzheimers Dement. 2012;8(2):121-30. doi: 10.1016/j.jalz.2011.01.007. Epub 2012 Feb 1. — View Citation

Porsteinsson AP, Drye LT, Pollock BG, Devanand DP, Frangakis C, Ismail Z, Marano C, Meinert CL, Mintzer JE, Munro CA, Pelton G, Rabins PV, Rosenberg PB, Schneider LS, Shade DM, Weintraub D, Yesavage J, Lyketsos CG; CitAD Research Group. Effect of citalopr — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	NeuroBehavior Rating Scale-- Agitation	NeuroBehavioral Rating Scale- Agitation(NBRS-A) assesses multiple types of psychopathology common in dementia and is based on a seven point Likert scale of increasing severity for each item(i.e., 0=not present, 1=very mild, 2-mild, 3=moderate, 4=moderately severe, 5=severe, 6=extremely severe). The NBRS agitation subscore includes NBRS 'inhibition', 'agitation', and 'hostility'. The range is 0 to 18 points. Higher scores indicate more symptoms.	9 weeks	No
Primary	Modified Alzheimer's Disease Cooperative Study- Clinical Global Impression of Change in Agitation(CGIC)	Modified Alzheimer's Disease Cooperative Study- Clinical Global Impression of Change in agitation(CGIC) accesses clinically significant change in agitation. A trained clinician, blind to treatment assignment, uses a 7-point Likert scale to rate change of each patient along a continuum from "marked improvement"(1), "no change"(4), and "marked worsening"(7). A number of aspects of the agitation is considered such as emotional agitation, mood liability/distress, psychomotor agitation, verbal aggression, and physical aggression. Range is 1-7.	Baseline to 9 weeks	No
Secondary	Cohen-Mansfield Agitation Inventory (CMAI)	CMAI examines several agitated behaviors including verbal, physical agitation, and other behaviors. Sub-items are summed. Range is 14-70. Higher scores indicate more severe symptoms.	9 weeks	No
Secondary	Neuropsychiatric Inventory (NPI)-- Agitation Subscore	NPI agitation score is based on responses from an informed caregiver involved in the patient's life. Symptom severity (1=mild, 2=moderate, 3=severe) is multiplied by frequency (1=occasionally, less than once/week; 4 = very frequently, once or more/day or continuously) to obtain the NPI agitation score.Range is 0-12. Higher scores indicate more severe symptoms.	9 weeks	No