Citalopram for Agitation in Alzheimer's Disease - Full Text View

Sponsor:	Johns Hopkins University
Collaborators:	National Institute on Aging (NIA) National Institute of Mental Health (NIMH)
Information provided by:	Johns Hopkins University
ClinicalTrials.gov Identifier:	NCT00898807

Purpose

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

Condition	Intervention	Phase
Alzheimer's Disease Agitation	Drug: citalopram Drug: placebo	Phase III

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor) Primary Purpose: Treatment
Official Title:	A Multi-Center Randomized Placebo-Controlled Clinical Trial Study of Citalopram for the Treatment of Agitation in Alzheimer's Disease

Resource links provided by NLM:

Genetics Home Reference related topics: Alzheimer disease

MedlinePlus related topics: Alzheimer's Disease Child Mental Health Dementia

Drug Information available for: Benzetimide Dexetimide Citalopram hydrobromide Citalopram Escitalopram Escitalopram oxalate

U.S. FDA Resources

Further study details as provided by Johns Hopkins University:

Primary Outcome Measures:

NeuroBehavior Rating Scale [ Time Frame: every 3 weeks over 9 weeks ] [ Designated as safety issue: No ]
CGIC [ Time Frame: Every 3 weeks over 9 weeks ] [ Designated as safety issue: No ]
Alzheimer's Disease Cooperative Study- Clinical Global Impression of Change

Secondary Outcome Measures:

Cohen-Mansfield Agitation Inventory [ Time Frame: every 3 weeks over 9 weeks ] [ Designated as safety issue: Yes ]
Rating scale for assessing the frequency with which people show certain behaviors. Total dose of lorazepam will also be recorded as well as any adverse events
Neuropsychiatric Inventory (NPI) [ Time Frame: every 3 weeks over 9 weeks ] [ Designated as safety issue: No ]

Estimated Enrollment:	200
Study Start Date:	July 2009
Estimated Study Completion Date:	September 2013
Estimated Primary Completion Date:	September 2013 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: Citalopram	Drug: citalopram target dose 30mg daily for 9 weeks Other Name: Celexa
Placebo Comparator: Placebo	Drug: placebo daily for 9 weeks

Detailed 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.

Eligibility

Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria

Probable Alzheimer's disease (NINCDS-ADRDA criteria), with MMSE 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 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 the 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 AD medication within the month preceding randomization, including starting, stopping, or dosage modifications

Exclusion criteria

Meets criteria for Major Depressive Episode by 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
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 (≥20 mg/day)
Treatment with a medication that would prohibit the safe concurrent use of citalopram, such as MAO inhibitors
Need for acute 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, ≤50 mg/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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00898807

Contacts

Contact: Anne Roche

410-550-9024

Locations

United States, California
University of Southern California Keck School of Medicine Memory and Aging Center	Recruiting
Los Angeles, California, United States, 90089
Contact: Mauricio Becerra 323-442-7594 mjbecerr@usc.edu
Contact: Liberty Teodoro, RN 323-442-7676 lteodoro@usc.edu
Principal Investigator: Lon S. Schneider, MD
Sub-Investigator: Bryan M. Spann, MD
VA Palo Alto Health Care System	Recruiting
Palo Alto, California, United States, 94304
Contact: Jeffrey Newell 650-493-5000 ext 67627 Jeffrey.Newell@va.gov
Contact: Emily Gere 650-852-3287 emilyg@stanford.edu
Principal Investigator: Jerome Yesavage, MD
Sub-Investigator: Vyjeyanthi S. Periyakoil, BS
United States, Maryland
Johns Hopkins University	Recruiting
Baltimore, Maryland, United States, 21224
Contact: Julia J Pedroso, RN, MA 410-550-9054 jpedroso@jhmi.edu
Contact: Anne E Roche, BS 410-550-9024 aroche3@jhmi.edu
Principal Investigator: Constantine Lyketsos, MD, MHS
Sub-Investigator: Paul Rosenberg, MD
Sub-Investigator: Christopher Marano, MD
United States, New York
Columbia University	Recruiting
New York, New York, United States, 10032
Contact: Karine Cunqueiro 212-543-6132 cunquei@pi.cpmc.columbia.edu
Contact: D. P. Devanand, MD 212-543-5612 dpd3@columbia.edu
Principal Investigator: D. P. Devanand, MD
Sub-Investigator: Gregory Pelton, MD
Monroe Community Hospital	Recruiting
Rochester, New York, United States, 14559
Contact: Bonnie Goldstein, MS, RN 585-760-6561 bonnies_goldstein@urcm.rochester.edu
Contact: Susan Salem-Spencer, BSN 585-760-6262 Ssalem-Spencer@urmc.rochester.edu
Principal Investigator: Anton Porsteinsson, MD
Sub-Investigator: M. Saleem Ismail, MD
United States, Pennsylvania
University of Pennsylvania, Section of Geriatric Psychiatry, Ralston House	Recruiting
Philadelphia, Pennsylvania, United States, 19104
Contact: Jamie Czerniakowski 215-349-8227 Jamie.czerniakowski@uphs.upenn.edu
Contact: Suzanne DiFilippo 215-349-8228 difilipp@mail.med.upenn.edu
Principal Investigator: Daniel Weintraub, MD
Sub-Investigator: Joel E. Streim, MD
United States, South Carolina
Medical University of South Carolina Alzheimer's Research and Clinical Programs	Recruiting
Charleston, South Carolina, United States, 29406
Contact: Caroline Mason, IMBA 843-740-1592 ext 14 masoncr@musc.edu
Principal Investigator: Jacobo E. Mintzer, MD
Sub-Investigator: Rhonda Weichsel, BS
Canada, Ontario
Centre for Addiction and Mental Health	Recruiting
Toronto, Ontario, Canada, M6J1H4
Contact: Bruce Pollock, MD 416-535-8501 ext 6595 bruce_pollock@camh.net
Contact: Dielle Miranda 416-535-8501 ext 3120 dielle_miranda@camh.net
Principal Investigator: Bruce Pollock, MD
Sub-Investigator: Benoit Mulsant, MD

Sponsors and Collaborators

Johns Hopkins University

National Institute on Aging (NIA)

National Institute of Mental Health (NIMH)

Investigators

Principal Investigator:	Constantine Lyketsos, MD, MHS	Johns Hopkins University
Study Director:	Lon Schneider, MD	University of Southern California Keck School of Medicine Memory and Aging Center
Study Director:	Bruce Pollock, MD	Centre for Addiction and Mental Health
Study Director:	Jacobo Mintzer, MD	Medical University of South Carolina Alzheimer's Research and Clinical Programs
Study Director:	Curtis Meinert, PhD	Johns Hopkins University

More Information

Publications:

Schneider LS, Tariot PN, Dagerman KS, Davis SM, Hsiao JK, Ismail MS, Lebowitz BD, Lyketsos CG, Ryan JM, Stroup TS, Sultzer DL, Weintraub D, Lieberman JA; CATIE-AD Study Group. Effectiveness of atypical antipsychotic drugs in patients with Alzheimer's disease. N Engl J Med. 2006 Oct 12;355(15):1525-38.

Steinberg M, Shao H, Zandi P, Lyketsos CG, Welsh-Bohmer KA, Norton MC, Breitner JC, Steffens DC, Tschanz JT; Cache County Investigators. Point and 5-year period prevalence of neuropsychiatric symptoms in dementia: the Cache County Study. Int J Geriatr Psychiatry. 2008 Feb;23(2):170-7.

Pollock BG, Mulsant BH, Rosen J, Sweet RA, Mazumdar S, Bharucha A, Marin R, Jacob NJ, Huber KA, Kastango KB, Chew ML. Comparison of citalopram, perphenazine, and placebo for the acute treatment of psychosis and behavioral disturbances in hospitalized, demented patients. Am J Psychiatry. 2002 Mar;159(3):460-5.

Responsible Party:	Constantine Lyketsos, MD, MHS, Johns Hopkins University
ClinicalTrials.gov Identifier:	NCT00898807 History of Changes
Other Study ID Numbers:	IA0155, R01AG031348
Study First Received:	May 11, 2009
Last Updated:	June 17, 2011
Health Authority:	United States: Institutional Review Board

Keywords provided by Johns Hopkins University:

BPSD
neuropsychiatric symptoms
aggression
mood lability

Additional relevant MeSH terms:

Alzheimer Disease
Psychomotor Agitation
Dementia
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Tauopathies
Neurodegenerative Diseases
Delirium, Dementia, Amnestic, Cognitive Disorders
Mental Disorders
Dyskinesias
Neurologic Manifestations
Psychomotor Disorders
Neurobehavioral Manifestations
Signs and Symptoms

Citalopram
Dexetimide
Antidepressive Agents, Second-Generation
Antidepressive Agents
Psychotropic Drugs
Central Nervous System Agents
Therapeutic Uses
Pharmacologic Actions
Serotonin Uptake Inhibitors
Neurotransmitter Uptake Inhibitors
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Serotonin Agents
Physiological Effects of Drugs
Antiparkinson Agents

ClinicalTrials.gov processed this record on February 09, 2012