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Citalopram for Agitation in Alzheimer's Disease (CitAD)

Primary Purpose

Alzheimer's Disease, Agitation

Status
Completed
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
citalopram
placebo
Sponsored by
JHSPH Center for Clinical Trials
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Alzheimer's Disease focused on measuring neuropsychiatric symptoms, aggression, mood lability

Eligibility Criteria

undefined - undefined (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • University of Southern California Keck School of Medicine Memory and Aging Center
  • VA Palo Alto Health Care System
  • Johns Hopkins University
  • Columbia University
  • Monroe Community Hospital
  • University of Pennsylvania, Section of Geriatric Psychiatry, Ralston House
  • Medical University of South Carolina Alzheimer's Research and Clinical Programs
  • Centre for Addiction and Mental Health

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Citalopram and psychosocial intervention

Placebo and psychosocial intervention

Arm Description

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

Matching placebo, oral, and psychosocial intervention

Outcomes

Primary Outcome Measures

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.
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.

Secondary Outcome Measures

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.
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.

Full Information

First Posted
May 11, 2009
Last Updated
June 26, 2014
Sponsor
JHSPH Center for Clinical Trials
Collaborators
National Institute on Aging (NIA), National Institute of Mental Health (NIMH)
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1. Study Identification

Unique Protocol Identification Number
NCT00898807
Brief Title
Citalopram for Agitation in Alzheimer's Disease
Acronym
CitAD
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

2. Study Status

Record Verification Date
June 2014
Overall Recruitment Status
Completed
Study Start Date
July 2009 (undefined)
Primary Completion Date
September 2013 (Actual)
Study Completion Date
September 2013 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
JHSPH Center for Clinical Trials
Collaborators
National Institute on Aging (NIA), National Institute of Mental Health (NIMH)

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Alzheimer's Disease, Agitation
Keywords
neuropsychiatric symptoms, aggression, mood lability

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
186 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Citalopram and psychosocial intervention
Arm Type
Experimental
Arm Description
Target dose of 30 mg per day of citalopram, oral, and psychosocial intervention
Arm Title
Placebo and psychosocial intervention
Arm Type
Placebo Comparator
Arm Description
Matching placebo, oral, and psychosocial intervention
Intervention Type
Drug
Intervention Name(s)
citalopram
Other Intervention Name(s)
Celexa
Intervention Description
target dose 30mg daily for 9 weeks
Intervention Type
Drug
Intervention Name(s)
placebo
Intervention Description
daily for 9 weeks
Primary Outcome Measure Information:
Title
NeuroBehavior Rating Scale-- Agitation
Description
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.
Time Frame
9 weeks
Title
Modified Alzheimer's Disease Cooperative Study- Clinical Global Impression of Change in Agitation(CGIC)
Description
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.
Time Frame
Baseline to 9 weeks
Secondary Outcome Measure Information:
Title
Cohen-Mansfield Agitation Inventory (CMAI)
Description
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.
Time Frame
9 weeks
Title
Neuropsychiatric Inventory (NPI)-- Agitation Subscore
Description
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.
Time Frame
9 weeks

10. Eligibility

Sex
All
Accepts Healthy Volunteers
No
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 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 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Constantine Lyketsos, MD, MHS
Organizational Affiliation
Johns Hopkins University
Official's Role
Study Chair
First Name & Middle Initial & Last Name & Degree
Lon Schneider, MD
Organizational Affiliation
University of Southern California Keck School of Medicine Memory and Aging Center
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Bruce Pollock, MD
Organizational Affiliation
Centre for Addiction and Mental Health
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Jacobo Mintzer, MD
Organizational Affiliation
Medical University of South Carolina Alzheimer's Research and Clinical Programs
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
David Shade, Esq
Organizational Affiliation
Johns Hopkins University
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Davengere Devanand, MD
Organizational Affiliation
Columbia University
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Paul Rosenberg, MD
Organizational Affiliation
Johns Hopkins University
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Daniel Weintraub, MD
Organizational Affiliation
University of Pennsylvania
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Anton Porsteinsson, MD
Organizational Affiliation
University of Rochester
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Jerome Yesavage, MD
Organizational Affiliation
Stanford University
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Southern California Keck School of Medicine Memory and Aging Center
City
Los Angeles
State/Province
California
ZIP/Postal Code
90089
Country
United States
Facility Name
VA Palo Alto Health Care System
City
Palo Alto
State/Province
California
ZIP/Postal Code
94304
Country
United States
Facility Name
Johns Hopkins University
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21224
Country
United States
Facility Name
Columbia University
City
New York
State/Province
New York
ZIP/Postal Code
10032
Country
United States
Facility Name
Monroe Community Hospital
City
Rochester
State/Province
New York
ZIP/Postal Code
14559
Country
United States
Facility Name
University of Pennsylvania, Section of Geriatric Psychiatry, Ralston House
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19104
Country
United States
Facility Name
Medical University of South Carolina Alzheimer's Research and Clinical Programs
City
Charleston
State/Province
South Carolina
ZIP/Postal Code
29406
Country
United States
Facility Name
Centre for Addiction and Mental Health
City
Toronto
State/Province
Ontario
ZIP/Postal Code
M6J1H4
Country
Canada

12. IPD Sharing Statement

Citations:
PubMed Identifier
22301195
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.
Results Reference
background
PubMed Identifier
24549548
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.
Results Reference
result
PubMed Identifier
24914549
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.
Results Reference
derived

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Citalopram for Agitation in Alzheimer's Disease

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