Treatment of Behavioral Symptoms in Alzheimer's Disease

Sponsor

New York State Psychiatric Institute (Other)

Overall Status

Completed

CT.gov ID

NCT00009217

Collaborator

National Institute of Mental Health (NIMH) (NIH)

Enrollment

Location

Arms

Duration (Months)

0.6

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Alzheimer's Disease Psychosis Agitation	Drug: Haloperidol-Haloperidol Drug: Haloperidol-Placebo	Phase 4

Detailed Description

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

44 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

Treatment of Behavioral Symptoms in Alzheimer's Disease

Study Start Date :

Jan 1, 1999

Actual Primary Completion Date :

Dec 1, 2004

Actual Study Completion Date :

Dec 1, 2004

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Haloperidol-Haloperidol Haloperidol for 20 weeks followed by haloperidol for 24 weeks	Drug: Haloperidol-Haloperidol Haloperidol open label flexible dose 1-5 mg daily for 20 weeks followed by haloperidol double-blind 1-5 mg for 24 weeks Other Names: Haldol
Placebo Comparator: Haloperidol-Placebo Haloperidol for 20 weeks followed by placebo for 24 weeks	Drug: Haloperidol-Placebo Haloperidol open-label flexible dose of 1-5 mg for 20 weeks followed by placebo double-blind for 24 weeks Other Names: Haldol

Arm

Intervention/Treatment

Active Comparator: Haloperidol-Haloperidol

Haloperidol for 20 weeks followed by haloperidol for 24 weeks

Drug: Haloperidol-Haloperidol

Haloperidol open label flexible dose 1-5 mg daily for 20 weeks followed by haloperidol double-blind 1-5 mg for 24 weeks

Other Names:

Haldol

Placebo Comparator: Haloperidol-Placebo

Haloperidol for 20 weeks followed by placebo for 24 weeks

Drug: Haloperidol-Placebo

Haloperidol open-label flexible dose of 1-5 mg for 20 weeks followed by placebo double-blind for 24 weeks

Other Names:

Haldol

Outcome Measures

Primary Outcome Measures

For the primary hypothesis, the primary endpoint is time to relapse. [0-24 weeks in Phase B]

Secondary Outcome Measures

Severity of target symptoms at the end of Phase A as a predictor of relapse [0-24 weeks in Phase B]
Severity of Brief Psychiatric Rating Scale psychosis and hostile suspiciousness factor scores [0-20 weeks in Phase A and 0-24 weeks in Phase B]
MMSE and Blessed Functional Activity Scale [0-20 weeks in Phase A and 0-24 weeks in Phase B]

Eligibility Criteria

Criteria

Ages Eligible for Study:

50 Years to 95 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Meets DSM-IV criteria for dementia either sex, age 50-95 years
Meets NINCDS-ADRDA criteria for probable Alzheimer's disease
Meets Folstein Mini-Mental State Exam score of 5-26, inclusive
Intellectual impairment reported for at least six months
Availability of family member who has had direct contact with the patient for an average of at least once every week during the three months prior to study entry
Has current symptoms of psychosis or agitation. Criteria for "psychosis" requires the presence of delusions and/or hallucinations identified by the Columbia University Scale for Psychopathology in Alzheimer's Disease (CUSPAD) and a minimum Brief Psychiatric Rating Scale (BPRS) psychosis factor score of at least 4 (moderate severity) on one of the following two items: These two items comprise the psychosis factor, excluding the item for conceptual disorganization. Agitation is defined as a score of greater than 3 (present at least 10 days per month) on one or more of the CERAD Behavioral Rating Scale for Dementia items for agitation, purposeless wandering, verbal aggression or physical aggression.
Free of psychotropic medication for at least two weeks prior to study entry, or able to tolerate medication washout for this period.
Informed consent by patient and family member, as per IRB procedures at New York State Psychiatric Institute.

Exclusion Criteria:

Acute unstable medical condition, delirium, alcohol or substance abuse or dependence within the past 1 year
Clinical evidence of stroke, other dementias including vascular or Lewy body or frontotemporal dementia, multiple sclerosis, Parkinson's disease, Huntington's disease, tardive dyskinesia
Diagnosis of a psychotic disorder antedating the onset of dementia
Antipsychotic medication usage during 4 weeks prior to study entry
Contraindication to the use of haloperidol