Treatment of Behavioral Symptoms in Alzheimer's Disease

May 23, 2016 updated by: New York State Psychiatric Institute

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 Overview

Status

Completed

Conditions

Intervention / Treatment

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 Type

Interventional

Enrollment (Actual)

44

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • New York
      • New York, New York, United States, 10032
        • New York State Psychiatric Institute

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

50 years to 95 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
For the primary hypothesis, the primary endpoint is time to relapse.
Time Frame: 0-24 weeks in Phase B
0-24 weeks in Phase B

Secondary Outcome Measures

Outcome Measure
Time Frame
Severity of target symptoms at the end of Phase A as a predictor of relapse
Time Frame: 0-24 weeks in Phase B
0-24 weeks in Phase B
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
0-20 weeks in Phase A and 0-24 weeks in Phase B
MMSE and Blessed Functional Activity Scale
Time Frame: 0-20 weeks in Phase A and 0-24 weeks in Phase B
0-20 weeks in Phase A and 0-24 weeks in Phase B

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

New York State Psychiatric Institute

Collaborators

National Institute of Mental Health (NIMH)

Investigators

  • Principal Investigator: Davangere Devanand, M.D., Columbia University College of Physicians and Surgeon

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

January 1, 1999

Primary Completion (Actual)

December 1, 2004

Study Completion (Actual)

December 1, 2004

Study Registration Dates

First Submitted

January 23, 2001

First Submitted That Met QC Criteria

January 23, 2001

First Posted (Estimate)

January 24, 2001

Study Record Updates

Last Update Posted (Estimate)

May 24, 2016

Last Update Submitted That Met QC Criteria

May 23, 2016

Last Verified

February 1, 2012

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • #4051R
  • R01MH055735 (U.S. NIH Grant/Contract)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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