Clinical trial NCT00898807: Citalopram for Agitation in Alzheimer's Disease
Official title: A Multi-Center Randomized Placebo-Controlled Clinical Trial Study of Citalopram for the Treatment of Agitation in Alzheimer's Disease
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Alzheimer's Disease
Agitation
Keywords: neuropsychiatric symptoms
aggression
mood lability
Lead sponsor: JHSPH Center for Clinical Trials
Sponsor class: OTHER
Collaborators: name: National Institute on Aging (NIA)
name: National Institute of Mental Health (NIMH)
First posted: 2009-05-12
Enrollment: 186
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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

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 criteria: 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

Primary outcomes:
measure: NeuroBehavior Rating Scale-- Agitation
timeFrame: 9 weeks
measure: Modified Alzheimer's Disease Cooperative Study- Clinical Global Impression of Change in Agitation(CGIC)
timeFrame: Baseline to 9 weeks
Secondary outcomes:
measure: Cohen-Mansfield Agitation Inventory (CMAI)
timeFrame: 9 weeks
measure: Neuropsychiatric Inventory (NPI)-- Agitation Subscore
timeFrame: 9 weeks
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: University of Southern California Keck School of Medicine Memory and Aging Center
state: California
city: Palo Alto
country: United States
facility: VA Palo Alto Health Care System
state: California
city: Baltimore
country: United States
facility: Johns Hopkins University
state: Maryland
city: New York
country: United States
facility: Columbia University
state: New York
city: Rochester
country: United States
facility: Monroe Community Hospital
state: New York
city: Philadelphia
country: United States
facility: University of Pennsylvania, Section of Geriatric Psychiatry, Ralston House
state: Pennsylvania
city: Charleston
country: United States
facility: Medical University of South Carolina Alzheimer's Research and Clinical Programs
state: South Carolina
city: Toronto
country: Canada
facility: Centre for Addiction and Mental Health
state: Ontario
Study officials:
affiliation: Johns Hopkins University
name: Constantine Lyketsos, MD, MHS
role: STUDY_CHAIR
affiliation: University of Southern California Keck School of Medicine Memory and Aging Center
name: Lon Schneider, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Centre for Addiction and Mental Health
name: Bruce Pollock, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Medical University of South Carolina Alzheimer's Research and Clinical Programs
name: Jacobo Mintzer, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Johns Hopkins University
name: David Shade, Esq
role: PRINCIPAL_INVESTIGATOR
affiliation: Columbia University
name: Davengere Devanand, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Johns Hopkins University
name: Paul Rosenberg, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Pennsylvania
name: Daniel Weintraub, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Rochester
name: Anton Porsteinsson, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Stanford University
name: Jerome Yesavage, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
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 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.
citation: 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.