Treatment of Behavioral Symptoms in Alzheimer's Disease
The optimal strategy for the treatment of behavioral complications in patients with probable Alzheimer's disease (AD) remains unclear.
The objective of this study is to evaluate the risk of relapse following discontinuation of haloperidol in patients with Alzheimer's disease (AD) with psychosis or agitation who respond to it.
In Phase A of this study, AD outpatients with behavioral complications receive 20 weeks of open haloperidol treatment with an oral dose of 1-5 mg daily, titrated individually to achieve the optimal trade-off between efficacy and side effects. Responders to Phase A participate in Phase B, a 24-week continuation trial in which patients are randomized to continuation haloperidol or placebo.
The primary outcome is the time to relapse of psychosis or behavioral disturbance.
|Study Design:||Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
|Official Title:||Treatment of Behavioral Symptoms in Alzheimer's Disease|
- For the primary hypothesis, the primary endpoint is time to relapse. [ Time Frame: 0-24 weeks in Phase B ] [ Designated as safety issue: No ]
- Severity of target symptoms at the end of Phase A as a predictor of relapse [ Time Frame: 0-24 weeks in Phase B ] [ Designated as safety issue: No ]
- Severity of Brief Psychiatric Rating Scale psychosis and hostile suspiciousness factor scores [ Time Frame: 0-20 weeks in Phase A and 0-24 weeks in Phase B ] [ Designated as safety issue: Yes ]
- MMSE and Blessed Functional Activity Scale [ Time Frame: 0-20 weeks in Phase A and 0-24 weeks in Phase B ] [ Designated as safety issue: Yes ]
|Study Start Date:||January 1999|
|Study Completion Date:||December 2004|
|Primary Completion Date:||December 2004 (Final data collection date for primary outcome measure)|
Active Comparator: Haloperidol-Haloperidol
Haloperidol for 20 weeks followed by haloperidol for 24 weeks
Haloperidol open label flexible dose 1-5 mg daily for 20 weeks followed by haloperidol double-blind 1-5 mg for 24 weeks
Other Name: Haldol
Placebo Comparator: Haloperidol-Placebo
Haloperidol for 20 weeks followed by placebo for 24 weeks
Haloperidol open-label flexible dose of 1-5 mg for 20 weeks followed by placebo double-blind for 24 weeks
Other Name: Haldol
The study involves two phases. Outpatients with AD who meet inclusion/ exclusion criteria enter Phase A, the 20 week open acute treatment phase that uses a flexible dose regimen of haloperidol 1-5 mg daily. Haloperidol is started at an oral dose of 1 mg daily, with subsequent dose titration in 1 mg increments until the optimal dose is reached, i.e., optimal trade-off between efficacy and side effects. At the end of Phase A, patients who do not meet criteria for clinical response exit the protocol and is treated openly with alternative medications.
Phase A responders enter Phase B, a 24-week random assignment, placebo-controlled, continuation trial. Randomization is stratified by the severity of dementia and by the presence of psychosis. Half the patients are randomized to haloperidol (continuing at the same dose as at the end of Phase A), and the other half are randomized to placebo. Patients who relapse during Phase B exit the protocol and receive open treatment.
In Phase A, patients are followed at 0, 2, 4 weeks and every 4 weeks thereafter until 20 weeks. In the discontinuation trial, Phase B, patients are followed at 0, 1, 2, 4, week time points and every 4 weeks thereafter until 24 weeks. If a patient shows signs of relapse, the patient is brought in for more frequent visits, regardless of the stage of the protocol.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00009217
|United States, New York|
|New York State Psychiatric Institute|
|New York, New York, United States, 10032|
|Principal Investigator:||Davangere Devanand, M.D.||Columbia University College of Physicians and Surgeon|