A Study of the Effectiveness and Safety of Risperidone in the Treatment of Behavioral Disturbances in Patients With Dementia

This study has been completed.
Information provided by:
Janssen Pharmaceutica N.V., Belgium
ClinicalTrials.gov Identifier:
First received: November 4, 2005
Last updated: January 13, 2011
Last verified: January 2011
The purpose of the study is to compare the safety and efficacy of risperidone (an antipsychotic medication) to that of placebo in the treatment of behavioral disturbances associated with dementia.

Condition Intervention Phase
Alzheimer Disease
Dementia, Vascular
Drug: risperidone
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double-Blind
Primary Purpose: Treatment
Official Title: Risperidone in the Treatment of Behavioral Disturbances in Demented Patients: an International, Multicenter, Placebo-controlled, Double-blind, Parallel-group Trial Using Haloperidol as Internal Reference

Resource links provided by NLM:

Further study details as provided by Janssen Pharmaceutica N.V., Belgium:

Primary Outcome Measures:
  • Change from baseline to end of double-blind treatment on the total BEHAVE-AD score.

Secondary Outcome Measures:
  • Change from baseline to end of double-blind treatment in global rating, total BEHAVE-AD score, total CMAI score, CGI severity, FAST, and MMSE; safety evaluations conducted throughout the study

Enrollment: 349
Study Start Date: April 1995
Study Completion Date: December 1996
Detailed Description:
Dementia is a term used for a collection of symptoms that can be caused by a number of diseases or injuries that affect the brain. Individuals with dementia have a loss of function in cognition (thinking, perception, learning, verbal communication, memory, judgment), which may lead to behavioral and personality changes (for example, agitation, delusions, hallucinations). Some causes of dementia are reversible; however, irreversible dementia is caused by certain conditions, such as Alzheimer's disease. Dementia is common in elderly individuals, but it is not a normal part of aging. This is a randomized, double-blind, parallel-group, placebo-controlled study comparing the effectiveness and safety of risperidone to placebo in patients with behavioral disturbances associated with dementia. Haloperidol is included as a reference therapy to confirm that the efficacy analyses are valid. The study is composed of two periods: a 1-week run-in period in which patients are discontinued from other antipsychotic drugs and take placebo twice daily and a 12-week double-blind treatment period. At the end of the run-in period, patients are randomly assigned to one of three risperidone doses, or placebo, or haloperidol (all oral solutions). The starting dose of risperidone and haloperidol is 0.25 milligrams (mg) twice daily, which is increased gradually to a maximum dose of 2 mg/day. If the patient does not have a sufficient response, the dose can be gradually increased to a maximum of 4 mg/day. The patient receives these doses for the remainder of the double-blind period. The primary measure of effectiveness is a reduction of >= 30% from baseline to the end of double-blind treatment on the total Behavior Pathology in Alzheimer's Disease Rating Scale (BEHAVE-AD) score. The BEHAVE-AD is a rating scale used to evaluate behavior symptoms in patients with Alzheimer's disease. Additional efficacy measures include the Clinical Global Impressions (CGI), a rating system used to evaluate the overall and severity of clinical change in a patient with various diseases affecting the brain; the Cohen-Mansfield Agitation Inventory (CMAI), a questionnaire evaluating agitation; the Functional Assessment Staging (FAST), a diagnostic tool for determining the stage of dementia; and the Mini-Mental State Examination (MMSE), a clinical measure used to evaluate cognition. Safety evaluations include the incidence of adverse events; results of clinical laboratory tests (hematology, biochemistry, urinalysis); measurements of vital signs; physical and neurological examinations and electrocardiogram (ECG) findings; evaluations of the presence and severity of sedation; a computed tomography (CT) scan of the brain; and the Extrapyramidal Symptoms Rating Scale (ESRS), a scale used to measure effects of antipsychotic medications on motor functions of the patient. The study hypothesis is that risperidone is more effective than placebo, as measured by a change from baseline on the total BEHAVE-AD score, in treating behavioral disturbances in demented patients. Risperidone oral solution 1 mg/mL; haloperidol oral solution, 1 mg/mL; placebo oral solution. Starting doses of 0.25 mg twice daily and increasing to 2 mg/day. If 2 mg/day shows an insufficient response, a maximum of 4 mg/day of risperidone or haloperidol is permitted. Total treatment duration is 12 weeks.

Ages Eligible for Study:   55 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Patients with dementia of the Alzheimer's type, mixed dementia, or vascular dementia, (as classified by the Diagnostic and Statistical Manual of Mental Diseases, 4th edition [DSM-IV]) and have behavioral disturbances
  • a score >=4 on the FAST
  • a score <=23 on the MMSE
  • a BEHAVE-AD total score >=8, and a BEHAVE-AD global rating >=1
  • must be institutionalized.

Exclusion Criteria:

  • Patients with other medical or neurological conditions in which cognition (thinking, perception, learning, verbal communication, memory, judgment) is diminished (for example, drug overdosage, severe liver, heart, lung, and kidney malfunctions, Parkinson's disease)
  • other psychiatric disorders, including major depression, schizophrenia, substance abuse or dependence
  • abnormal electrocardiogram (ECG) findings
  • abnormal clinical laboratory test findings.
  Contacts and Locations
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Please refer to this study by its ClinicalTrials.gov identifier: NCT00249145

Sponsors and Collaborators
Janssen Pharmaceutica N.V., Belgium
Study Director: Janssen Pharmaceutica N.V. Clinical Trial Janssen Pharmaceutica N.V.
  More Information

ClinicalTrials.gov Identifier: NCT00249145     History of Changes
Other Study ID Numbers: CR006046 
Study First Received: November 4, 2005
Last Updated: January 13, 2011
Health Authority: Belgium: Ministry of Social Affairs, Public Health and the Environment

Keywords provided by Janssen Pharmaceutica N.V., Belgium:
Alzheimer's Disease
vascular dementia
mixed dementia, risperidone
nursing home

Additional relevant MeSH terms:
Dementia, Vascular
Alzheimer Disease
Problem Behavior
Arterial Occlusive Diseases
Behavioral Symptoms
Brain Diseases
Cardiovascular Diseases
Central Nervous System Diseases
Cerebrovascular Disorders
Intracranial Arterial Diseases
Intracranial Arteriosclerosis
Mental Disorders
Nervous System Diseases
Neurocognitive Disorders
Neurodegenerative Diseases
Vascular Diseases
Antipsychotic Agents
Central Nervous System Depressants
Dopamine Agents
Dopamine Antagonists
Molecular Mechanisms of Pharmacological Action
Neurotransmitter Agents
Physiological Effects of Drugs
Psychotropic Drugs
Serotonin Agents

ClinicalTrials.gov processed this record on May 25, 2016