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Citalopram for Agitation in Alzheimer's Disease (CitAD)

This study has been completed.
Sponsor:
Collaborators:
Information provided by (Responsible Party):
Dave Shade, Johns Hopkins University
ClinicalTrials.gov Identifier:
NCT00898807
First received: May 11, 2009
Last updated: June 26, 2014
Last verified: June 2014

May 11, 2009
June 26, 2014
July 2009
September 2013   (final data collection date for primary outcome measure)
  • NeuroBehavior Rating Scale-- Agitation [ Time Frame: 9 weeks ] [ Designated as safety issue: No ]
    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.
  • Modified Alzheimer's Disease Cooperative Study- Clinical Global Impression of Change in Agitation(CGIC) [ Time Frame: Baseline to 9 weeks ] [ Designated as safety issue: No ]
    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.
NeuroBehavior Rating Scale [ Time Frame: every 3 weeks over 9 weeks ] [ Designated as safety issue: No ]
Complete list of historical versions of study NCT00898807 on ClinicalTrials.gov Archive Site
  • Cohen-Mansfield Agitation Inventory (CMAI) [ Time Frame: 9 weeks ] [ Designated as safety issue: No ]
    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.
  • Neuropsychiatric Inventory (NPI)-- Agitation Subscore [ Time Frame: 9 weeks ] [ Designated as safety issue: No ]
    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.
  • Alzheimer's Disease Cooperative Study-Clinical Global Impression Of Change (ADCS-CGIC), modified [ Time Frame: every 3 weeks over 9 weeks ] [ Designated as safety issue: No ]
  • Neuropsychiatric Inventory (NPI) [ Time Frame: every 3 weeks over 9 weeks ] [ Designated as safety issue: No ]
  • Udvalg for Kliniske Undersogelser (UKU) side effects rating scale [ Time Frame: every 3 weeks over 9 weeks ] [ Designated as safety issue: No ]
Not Provided
Not Provided
 
Citalopram for Agitation in Alzheimer's Disease
A Multi-Center Randomized Placebo-Controlled Clinical Trial Study of Citalopram for the Treatment of Agitation in Alzheimer's Disease

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

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.

Interventional
Phase 3
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
  • Alzheimer's Disease
  • Agitation
  • Drug: citalopram
    target dose 30mg daily for 9 weeks
    Other Name: Celexa
  • Drug: placebo
    daily for 9 weeks
  • Experimental: Citalopram and psychosocial intervention
    Target dose of 30 mg per day of citalopram, oral, and psychosocial intervention
    Intervention: Drug: citalopram
  • Placebo Comparator: Placebo and psychosocial intervention
    Matching placebo, oral, and psychosocial intervention
    Intervention: Drug: placebo

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
186
September 2013
September 2013   (final data collection date for primary outcome measure)

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
Both
Not Provided
No
Contact information is only displayed when the study is recruiting subjects
United States,   Canada
 
NCT00898807
IA0155, R01AG031348
Yes
Dave Shade, Johns Hopkins University
JHSPH Center for Clinical Trials
  • National Institute on Aging (NIA)
  • National Institute of Mental Health (NIMH)
Study Chair: Constantine Lyketsos, MD, MHS Johns Hopkins University
Principal Investigator: 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
JHSPH Center for Clinical Trials
June 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP