Trial Outcomes & Findings for Citalopram for Agitation in Alzheimer's Disease (NCT NCT00898807)

Last Updated: 2014-06-27

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

186 participants

Primary outcome timeframe

9 weeks

Results posted on

2014-06-27

Participant Flow

Recruitment activities included chart review, telephone interviews and screens, discussion with physicians, and recruitment in the clinic waiting areas and assisted living facilities affiliated with the clinics. The recruitment period lasted from August 2009 to December 2012.

Participant milestones

Participant milestones
Measure	Citalopram and Psychosocial Intervention Target dose of 30 mg per day of citalopram, oral, and psychosocial intervention citalopram : target dose 30mg daily for 9 weeks	Placebo and Psychosocial Intervention Matching placebo, oral, and psychosocial intervention placebo : daily for 9 weeks
Overall Study STARTED	94	92
Overall Study COMPLETED	86	83
Overall Study NOT COMPLETED	8	9

Reasons for withdrawal

Reasons for withdrawal
Measure	Citalopram and Psychosocial Intervention Target dose of 30 mg per day of citalopram, oral, and psychosocial intervention citalopram : target dose 30mg daily for 9 weeks	Placebo and Psychosocial Intervention Matching placebo, oral, and psychosocial intervention placebo : daily for 9 weeks
Overall Study Withdrawal by Subject	5	3
Overall Study Family pressure to discontinue	2	2
Overall Study Lost to Follow-up	1	3
Overall Study Death	0	1

Baseline Characteristics

Citalopram for Agitation in Alzheimer's Disease

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Citalopram and Psychosocial Intervention n=94 Participants Target dose of 30 mg per day of citalopram, oral, and psychosocial intervention citalopram : target dose 30mg daily for 9 weeks	Placebo and Psychosocial Intervention n=92 Participants Matching placebo, oral, and psychosocial intervention placebo : daily for 9 weeks	Total n=186 Participants Total of all reporting groups
Sex: Female, Male Male	50 Participants n=5 Participants	51 Participants n=7 Participants	101 Participants n=5 Participants
Region of Enrollment United States	82 participants n=5 Participants	79 participants n=7 Participants	161 participants n=5 Participants
Region of Enrollment Canada	12 participants n=5 Participants	13 participants n=7 Participants	25 participants n=5 Participants
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	6 Participants n=5 Participants	7 Participants n=7 Participants	13 Participants n=5 Participants
Age, Categorical >=65 years	88 Participants n=5 Participants	85 Participants n=7 Participants	173 Participants n=5 Participants
Age, Continuous	78 years STANDARD_DEVIATION 9 • n=5 Participants	79 years STANDARD_DEVIATION 8 • n=7 Participants	78 years STANDARD_DEVIATION 8 • n=5 Participants
Sex: Female, Male Female	44 Participants n=5 Participants	41 Participants n=7 Participants	85 Participants n=5 Participants

PRIMARY outcome

Timeframe: 9 weeks

Population: 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.

Outcome measures

Outcome measures
Measure	Citalopram and Psychosocial Intervention n=90 Participants Target dose of 30 mg per day of citalopram, oral, and psychosocial intervention citalopram : target dose 30mg daily for 9 weeks	Placebo and Psychosocial Intervention n=85 Participants Matching placebo, oral, and psychosocial intervention placebo : daily for 9 weeks
NeuroBehavior Rating Scale-- Agitation	4.33 units on a scale Standard Error 0.31	5.26 units on a scale Standard Error 0.31

PRIMARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Citalopram and Psychosocial Intervention n=86 Participants Target dose of 30 mg per day of citalopram, oral, and psychosocial intervention citalopram : target dose 30mg daily for 9 weeks	Placebo and Psychosocial Intervention n=81 Participants Matching placebo, oral, and psychosocial intervention placebo : daily for 9 weeks
Modified Alzheimer's Disease Cooperative Study- Clinical Global Impression of Change in Agitation(CGIC)	40 percentage moderate/marked improvement	26 percentage moderate/marked improvement

SECONDARY outcome

Timeframe: 9 weeks

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.

Outcome measures

Outcome measures
Measure	Citalopram and Psychosocial Intervention n=90 Participants Target dose of 30 mg per day of citalopram, oral, and psychosocial intervention citalopram : target dose 30mg daily for 9 weeks	Placebo and Psychosocial Intervention n=85 Participants Matching placebo, oral, and psychosocial intervention placebo : daily for 9 weeks
Cohen-Mansfield Agitation Inventory (CMAI)	27.7 units on a scale Standard Deviation 6.7	28.7 units on a scale Standard Deviation 6.7

SECONDARY outcome

Timeframe: 9 weeks

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.

Outcome measures

Outcome measures
Measure	Citalopram and Psychosocial Intervention n=90 Participants Target dose of 30 mg per day of citalopram, oral, and psychosocial intervention citalopram : target dose 30mg daily for 9 weeks	Placebo and Psychosocial Intervention n=85 Participants Matching placebo, oral, and psychosocial intervention placebo : daily for 9 weeks
Neuropsychiatric Inventory (NPI)-- Agitation Subscore	7.8 units on a scale Standard Deviation 2.2	8.0 units on a scale Standard Deviation 2.4

Adverse Events

Citalopram and Psychosocial Intervention

Serious events: 8 serious events

Other events: 90 other events

Deaths: 0 deaths

Placebo and Psychosocial Intervention

Serious events: 7 serious events

Other events: 86 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Citalopram and Psychosocial Intervention n=90 participants at risk；n=94 participants at risk Target dose of 30 mg per day of citalopram, oral, and psychosocial intervention citalopram : target dose 30mg daily for 9 weeks	Placebo and Psychosocial Intervention n=86 participants at risk；n=92 participants at risk Matching placebo, oral, and psychosocial intervention placebo : daily for 9 weeks
Psychiatric disorders Mental status change	1.1% 1/94 Adverse events (AEs) are collected systematically on the follow-up visit form; therefore, numbers of participants at risk for AEs reflect at least on follow-up visit form completed. Serious adverse events are often self-reported and can be collected any time throughout the study.	2.2% 2/92 Adverse events (AEs) are collected systematically on the follow-up visit form; therefore, numbers of participants at risk for AEs reflect at least on follow-up visit form completed. Serious adverse events are often self-reported and can be collected any time throughout the study.
Infections and infestations Sepsis	1.1% 1/94 Adverse events (AEs) are collected systematically on the follow-up visit form; therefore, numbers of participants at risk for AEs reflect at least on follow-up visit form completed. Serious adverse events are often self-reported and can be collected any time throughout the study.	0.00% 0/92 Adverse events (AEs) are collected systematically on the follow-up visit form; therefore, numbers of participants at risk for AEs reflect at least on follow-up visit form completed. Serious adverse events are often self-reported and can be collected any time throughout the study.
Respiratory, thoracic and mediastinal disorders Pneumonia	1.1% 1/94 Adverse events (AEs) are collected systematically on the follow-up visit form; therefore, numbers of participants at risk for AEs reflect at least on follow-up visit form completed. Serious adverse events are often self-reported and can be collected any time throughout the study.	0.00% 0/92 Adverse events (AEs) are collected systematically on the follow-up visit form; therefore, numbers of participants at risk for AEs reflect at least on follow-up visit form completed. Serious adverse events are often self-reported and can be collected any time throughout the study.
Psychiatric disorders Increased agitation	1.1% 1/94 Adverse events (AEs) are collected systematically on the follow-up visit form; therefore, numbers of participants at risk for AEs reflect at least on follow-up visit form completed. Serious adverse events are often self-reported and can be collected any time throughout the study.	2.2% 2/92 Adverse events (AEs) are collected systematically on the follow-up visit form; therefore, numbers of participants at risk for AEs reflect at least on follow-up visit form completed. Serious adverse events are often self-reported and can be collected any time throughout the study.
Nervous system disorders Fall	1.1% 1/94 Adverse events (AEs) are collected systematically on the follow-up visit form; therefore, numbers of participants at risk for AEs reflect at least on follow-up visit form completed. Serious adverse events are often self-reported and can be collected any time throughout the study.	1.1% 1/92 Adverse events (AEs) are collected systematically on the follow-up visit form; therefore, numbers of participants at risk for AEs reflect at least on follow-up visit form completed. Serious adverse events are often self-reported and can be collected any time throughout the study.
Cardiac disorders Hypotension	1.1% 1/94 Adverse events (AEs) are collected systematically on the follow-up visit form; therefore, numbers of participants at risk for AEs reflect at least on follow-up visit form completed. Serious adverse events are often self-reported and can be collected any time throughout the study.	0.00% 0/92 Adverse events (AEs) are collected systematically on the follow-up visit form; therefore, numbers of participants at risk for AEs reflect at least on follow-up visit form completed. Serious adverse events are often self-reported and can be collected any time throughout the study.
Cardiac disorders Chest pain	1.1% 1/94 Adverse events (AEs) are collected systematically on the follow-up visit form; therefore, numbers of participants at risk for AEs reflect at least on follow-up visit form completed. Serious adverse events are often self-reported and can be collected any time throughout the study.	0.00% 0/92 Adverse events (AEs) are collected systematically on the follow-up visit form; therefore, numbers of participants at risk for AEs reflect at least on follow-up visit form completed. Serious adverse events are often self-reported and can be collected any time throughout the study.
Infections and infestations Surgical removal of infected plate in wrist	1.1% 1/94 Adverse events (AEs) are collected systematically on the follow-up visit form; therefore, numbers of participants at risk for AEs reflect at least on follow-up visit form completed. Serious adverse events are often self-reported and can be collected any time throughout the study.	0.00% 0/92 Adverse events (AEs) are collected systematically on the follow-up visit form; therefore, numbers of participants at risk for AEs reflect at least on follow-up visit form completed. Serious adverse events are often self-reported and can be collected any time throughout the study.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Lung cancer	0.00% 0/94 Adverse events (AEs) are collected systematically on the follow-up visit form; therefore, numbers of participants at risk for AEs reflect at least on follow-up visit form completed. Serious adverse events are often self-reported and can be collected any time throughout the study.	1.1% 1/92 Adverse events (AEs) are collected systematically on the follow-up visit form; therefore, numbers of participants at risk for AEs reflect at least on follow-up visit form completed. Serious adverse events are often self-reported and can be collected any time throughout the study.
Musculoskeletal and connective tissue disorders Abdominal pain	0.00% 0/94 Adverse events (AEs) are collected systematically on the follow-up visit form; therefore, numbers of participants at risk for AEs reflect at least on follow-up visit form completed. Serious adverse events are often self-reported and can be collected any time throughout the study.	1.1% 1/92 Adverse events (AEs) are collected systematically on the follow-up visit form; therefore, numbers of participants at risk for AEs reflect at least on follow-up visit form completed. Serious adverse events are often self-reported and can be collected any time throughout the study.

Other adverse events

Additional Information

Anne Casper

Johns Hopkins

Phone: 410-955-8183

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place