Citalopram for Agitation in Alzheimer's Disease

NCT00898807 | Completed Phase 3 Results DMC

• 2 other identifiers: IA0155R01AG031348
• Study Type: interventional
• Target: 186
• Locations: 2 countries
• Sites: 8

Brief Summary

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

Conditions

Alzheimer's Disease; Agitation

Keywords

neuropsychiatric symptoms; aggression; mood lability

Outcome Measures

Primary Outcomes (2)

• 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

• 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

Secondary Outcomes (2)

• Cohen-Mansfield Agitation Inventory (CMAI)

  9 weeks

• Neuropsychiatric Inventory (NPI)-- Agitation Subscore

  9 weeks

Study Arms (2)

Citalopram and psychosocial intervention

EXPERIMENTAL

Target dose of 30 mg per day of citalopram, oral, and psychosocial intervention

Drug: citalopram

Placebo and psychosocial intervention

PLACEBO COMPARATOR

Matching placebo, oral, and psychosocial intervention

Drug: placebo

Interventions

citalopram DRUG

target dose 30mg daily for 9 weeks

Also known as: Celexa

Citalopram and psychosocial intervention

placebo DRUG

daily for 9 weeks

Placebo and psychosocial intervention

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• 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

Sponsors & Collaborators

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

Study Sites (8)

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

Los Angeles, California, 90089, United States

Location

VA Palo Alto Health Care System

Palo Alto, California, 94304, United States

Location

Johns Hopkins University

Baltimore, Maryland, 21224, United States

Location

Columbia University

New York, New York, 10032, United States

Location

Monroe Community Hospital

Rochester, New York, 14559, United States

Location

University of Pennsylvania, Section of Geriatric Psychiatry, Ralston House

Philadelphia, Pennsylvania, 19104, United States

Location

Medical University of South Carolina Alzheimer's Research and Clinical Programs

Charleston, South Carolina, 29406, United States

Location

Centre for Addiction and Mental Health

Toronto, Ontario, M6J1H4, Canada

Location

Related Publications (3)

• 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.

  PMID: 22301195 BACKGROUND

• 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 citalopram on agitation in Alzheimer disease: the CitAD randomized clinical trial. JAMA. 2014 Feb 19;311(7):682-91. doi: 10.1001/jama.2014.93.

  PMID: 24549548 RESULT

• Drye LT, Spragg D, Devanand DP, Frangakis C, Marano C, Meinert CL, Mintzer JE, Munro CA, Pelton G, Pollock BG, Porsteinsson AP, Rabins PV, Rosenberg PB, Schneider LS, Shade DM, Weintraub D, Yesavage J, Lyketsos CG; CitAD Research Group. Changes in QTc interval in the citalopram for agitation in Alzheimer's disease (CitAD) randomized trial. PLoS One. 2014 Jun 10;9(6):e98426. doi: 10.1371/journal.pone.0098426. eCollection 2014.

  PMID: 24914549 DERIVED

MeSH Terms

Conditions

Alzheimer Disease; Psychomotor Agitation; Aggression

Interventions

Citalopram

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

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

Results Point of Contact

• Title: Anne Casper
• Organization: Johns Hopkins

ashankl1@jhu.edu

410-955-8183

Study Officials

• Constantine Lyketsos, MD, MHS

  Johns Hopkins University

  STUDY CHAIR

• Lon Schneider, MD

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

  PRINCIPAL INVESTIGATOR

• Bruce Pollock, MD

  Centre for Addiction and Mental Health

  PRINCIPAL INVESTIGATOR

• Jacobo Mintzer, MD

  Medical University of South Carolina Alzheimer's Research and Clinical Programs

  PRINCIPAL INVESTIGATOR

• David Shade, Esq

  Johns Hopkins University

  PRINCIPAL INVESTIGATOR

• Davengere Devanand, MD

  Columbia University

  PRINCIPAL INVESTIGATOR

• Paul Rosenberg, MD

  Johns Hopkins University

  PRINCIPAL INVESTIGATOR

• Daniel Weintraub, MD

  University of Pennsylvania

  PRINCIPAL INVESTIGATOR

• Anton Porsteinsson, MD

  University of Rochester

  PRINCIPAL INVESTIGATOR

• Jerome Yesavage, MD

  Stanford University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

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

Study Record Dates

• First Submitted: May 11, 2009
• First Posted: May 12, 2009
• Study Start: July 1, 2009
• Primary Completion: September 1, 2013
• Study Completion: September 1, 2013
• Last Updated: June 27, 2014
• Results First Posted: June 27, 2014

Record last verified: 2014-06

Locations

CA (1); US (7)