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.

Study Type: Interventional

Study Design: Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Study Primary Completion Date: September 2013

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.

Intervention(s) in this Clinical Trial

• Drug: citalopram
  • target dose 30mg daily for 9 weeks
• Drug: placebo
  • daily for 9 weeks

Arms, Groups and Cohorts in this Clinical Trial

• Experimental: Citalopram
• Placebo Comparator: Placebo

Primary Measures

• NeuroBehavior Rating Scale
  • Time Frame: every 3 weeks over 9 weeks
    Safety Issue?: No
• CGIC
  • Time Frame: Every 3 weeks over 9 weeks
    Safety Issue?: No

Secondary Measures

• Cohen-Mansfield Agitation Inventory
  • Time Frame: Weekly x 3 wks then every10 d to 9 wks
    Safety Issue?: Yes
• Neuropsychiatric Inventory (NPI)
  • Time Frame: every 3 weeks over 9 weeks
    Safety Issue?: No

Inclusion Criteria:

• Probable Alzheimer's disease (NINCDS-ADRDA criteria), with MMSE score of 5-26 inclusive
• Clinically significant agitation for which 1) a medication is needed;in the opinion of the study physician 2) score ≥ 4 on the Neuropsychiatric Inventory (NPI) agitation domain; 3) more than 2 agitated behaviors per week as assessed on the NPI
• Provision of informed consent for participation in the study by patient,caregiver or surrogate (if necessary).
• 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
• Sufficient fluency, of the patient and caregiver, in written and spoken English or Spanish to participate in study visits, neuropsychological testing, and other outcome assessments
• If on treatment for AD, stability of treatment (i.e. memantine or cholinesterase inhibitors), no changes to AD medications (e.g. starting or stopping treatment) in the 3 months prior to randomization, with the exception that dose adjustments within the therapeutic range (i.e., total daily dose of greater than or equal to 10mg memantine, greater than or equal to 5 mg. of donepezil, greater than or equal to 16mg per day of galantamine, or greater than or equal to 4mg per day of rivastigmine) are allowed as long as 1) the patient has received the minimum therapeutic range dose or higher for at least 3 months; 2) the last dose change was at least 1 month prior to randomization; and 3) no further dose adjustments are planned during the study's treatment phase.
• Stable treatment for AD with cholinesterase inhibitors and/or memantine

Exclusion Criteria:

• Meets criteria for Major Depressive Episode by DSM-IV(TR) criteria
• Presence of a brain disease that might otherwise fully 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
• 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 20mg/day)
• Treatment with a medication that would prohibit the safe concurrent use of citalopram, such as MAO inhibitors
• Need for psychiatric hospitalization, or acutely 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 antidepressants (other than trazodone, less than or equal to 50 mg per day at bedtime), benzodiazepines (other than lorazepam), or psychostimulants
• Any condition that makes it medically inappropriate or risky for the patient to enroll in the trial

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: N/A

Maximum Age for this Clinical Trial: N/A

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: Johns Hopkins University

Overall Clinical Trial Officials and Contacts

Constantine Lyketsos, MD, MHS Principal Investigator Johns Hopkins University  

Overall Contact: Kristine Boehmer 410-550-9024 khalter1@jhmi.edu

Information obtained from ClinicalTrials.gov on September 01, 2010

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00898807

Study ID Number: IA0155

ClinicalTrials.gov Identifier: NCT00898807

Health Authority: United States: Institutional Review Board