Alzheimer's DiseasePhase 3CitADNCT00898807

Citalopram for Agitation in Alzheimer's Disease

A Phase 3 study testing citalopram in people with Alzheimer's Disease and Agitation, run by JHSPH Center for Clinical Trials at 8 sites in 2 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

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

Who is it for?: Any age
Conditions the study is for: Alzheimer's Disease, Agitation
What is being tested?: citalopram
Type of treatment: Pill or oral medicine
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 186 participants
Where: 8 sitesin 2 countries
Study dates: Jul 2009to Sep 2013
Phase: Phase 3
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages Any age
All sexes
No healthy volunteers
Child, Adult, Older adult

Who may be able to join

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

Who cannot join

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)

Show all 11Show fewer

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

Trial locations and contacts

8 sites in 2 countries.

Country

City, postcode or hospital

8 sites in 2 countries

United States7 sites

Johns Hopkins University
Baltimore, Maryland, 21224
Medical University of South Carolina Alzheimer's Research and Clinical Programs
Charleston, South Carolina, 29406
University of Southern California Keck School of Medicine Memory and Aging Center
Los Angeles, California, 90089
Columbia University
New York, New York, 10032
VA Palo Alto Health Care System
Palo Alto, California, 94304
University of Pennsylvania, Section of Geriatric Psychiatry, Ralston House
Philadelphia, Pennsylvania, 19104
Monroe Community Hospital
Rochester, New York, 14559

Other trials in United States

Canada1 site

Centre for Addiction and Mental Health
Toronto, Ontario, M6J1H4

Other trials in Canada

About this study

Official title: 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.

Read the 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.

Conditions: Alzheimer's Disease, Agitation
Being tested: citalopram, placebo
Keywords: neuropsychiatric symptoms, aggression, mood lability
Medical subject headings: Alzheimer Disease, Psychomotor Agitation, Aggression

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

citalopramDrug
Also called Celexa
target dose 30mg daily for 9 weeks
placeboDrug
daily for 9 weeks

Study groups in NCT00898807
Study group	Role	What they receive
Citalopram and psychosocial intervention	Experimental	Target dose of 30 mg per day of citalopram, oral, and psychosocial intervention Receives: Drug: citalopram
Placebo and psychosocial intervention	Placebo comparator	Matching placebo, oral, and psychosocial intervention Receives: Drug: placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

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.
Measured: 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.
Measured: Baseline to 9 weeks

Secondary outcomes (2)

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.
Measured: 9 weeks
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.
Measured: 9 weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Jul 2009Sep 2013

First posted12 May 2009 (estimated)
Study startJul 2009
Primary completionSep 2013
Study completionSep 2013

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (3)Papers the sponsor has linked to this study.
Other trials for Alzheimer's DiseaseStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 3
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Quadruple blind
Who is masked: Participant, Care provider, Investigator, Outcomes assessor
Enrolment: 186 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT00898807
Sponsor's protocol ID: IA0155
Other IDs: R01AG031348
Acronym: CitAD
Status last verified: Jun 2014
First submitted: 11 May 2009
Last updated: 27 Jun 2014
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes

Publications

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.
PubMed 22301195
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.
PubMed 24549548
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.
PubMed 24914549

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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Study at a glance

From the registry record, last updated by the sponsor on 27 Jun 2014. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Multi-Center Randomized Placebo-Controlled Clinical Trial Study of Citalopram for the Treatment of Agitation in Alzheimer's Disease
ClinicalTrials.gov ID: NCT00898807
Acronym / sponsor ID: CitAD / IA0155
Conditions: Alzheimer's Disease, Agitation
Keywords: neuropsychiatric symptoms, aggression, mood lability
Phase: Phase 3
Study type: Interventional
Recruitment status: Completed
Enrolment: 186 participants (actual)
Lead sponsor: JHSPH Center for Clinical TrialsUniversity, hospital or other
Collaborators: National Institute on Aging (NIA), National Institute of Mental Health (NIMH)
Study start: Jul 2009
Primary completion: Sep 2013 (actual)
Study completion: Sep 2013 (actual)
First posted: 12 May 2009 (estimated)
Results: Posted 27 Jun 2014

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

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

Detailed description

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Quadruple blind (participant, care provider, investigator, outcomes assessor)
Number of arms: 2

Arm	Type	Receives
Citalopram and psychosocial intervention	Experimental	Drug: citalopramTarget dose of 30 mg per day of citalopram, oral, and psychosocial intervention
Placebo and psychosocial intervention	Placebo comparator	Drug: placeboMatching placebo, oral, and psychosocial intervention

Who may qualify

Sex: All
Healthy volunteers: Not accepted
Age groups: Child, Adult, Older adult

Key inclusion criteria (8 listed)

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
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

Key exclusion criteria (11 listed)

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

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
citalopramAlso: Celexatarget dose 30mg daily for 9 weeks	Drug	Citalopram and psychosocial intervention
placebodaily for 9 weeks	Drug	Placebo and psychosocial intervention

Primary outcome

NeuroBehavior Rating Scale-- Agitation
Time frame: 9 weeks
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
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.

2 secondary outcomes

Cohen-Mansfield Agitation Inventory (CMAI)
Time frame: 9 weeks
Neuropsychiatric Inventory (NPI)-- Agitation Subscore
Time frame: 9 weeks

Results and safety

Results posted to the registry on 27 Jun 2014, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Citalopram and Psychosocial Intervention	94	86
Placebo and Psychosocial Intervention	92	83

Primary outcome: NeuroBehavior Rating Scale-- Agitation

Time frame: 9 weeks. Mean (Standard Error). Unit: units on a scale

Measure	Citalopram and Psychosocial Intervention n = 90	Placebo and Psychosocial Intervention n = 85
Value	4.33 (0.31)	5.26 (0.31)

Citalopram and Psychosocial Intervention vs Placebo and Psychosocial Intervention: Mean Difference (Net): -0.93 (95% CI -1.80 to -0.06), p = 0.036, Mixed Models Analysis

Population analysed: The primary analysis was an intention-to-treat analysis; analysis was conducted "as randomized". Data from the 186 randomized participants were used in the analytic model. 167 of the 186 patients had week 9 data on the NBRS.

Primary outcome: Modified Alzheimer's Disease Cooperative Study- Clinical Global Impression of Change in Agitation(CGIC)

Time frame: Baseline to 9 weeks. Number. Unit: percentage moderate/marked improvement

Measure	Citalopram and Psychosocial Intervention n = 86	Placebo and Psychosocial Intervention n = 81
Value	40	26

Citalopram and Psychosocial Intervention vs Placebo and Psychosocial Intervention: Odds Ratio (OR): 2.13 (95% CI 1.23 to 3.69), p = 0.007, Proportional odds

2 secondary outcomes are reported in the full results.

Adverse events

Other adverse events reported at 1% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Citalopram and Psychosocial Intervention	8 of 94 (8.5%)	90 of 90 (100%)	Not reported
Placebo and Psychosocial Intervention	7 of 92 (7.6%)	86 of 86 (100%)	Not reported

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 27 Jun 2014.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Background: PubMed 22301195Drye 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 publication: PubMed 24549548Porsteinsson 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.
Derived from this study: PubMed 24914549Drye 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.

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Constantine Lyketsos, MD, MHS study chair

Johns Hopkins University

Lon Schneider, MD principal investigator

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

Bruce Pollock, MD principal investigator

Centre for Addiction and Mental Health

8 sites in 2 countries: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing citalopram in people with Alzheimer's Disease and Agitation, run by JHSPH Center for Clinical Trials at 8 sites in 2 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 8 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 27 Jun 2014. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 8 sites in United States, Canada. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 27 Jun 2014). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

NeuroBehavior Rating Scale-- Agitation (time frame: 9 weeks). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00898807, which also lists 3 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Jun 2014.