Antipsychotic Discontinuation in Alzheimer's Disease - Clinical Trial for Alzheimer Disease | NCT00417482

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Primary Purpose

Status

Completed

Phase

Phase 4

Locations

United States

Study Type

Interventional

Intervention

risperidone

About this trial

This is an interventional treatment trial for Alzheimer Disease focused on measuring Risperidone treatment, psychosis, agitation, aggression,, discontinuation, placebo

Eligibility Criteria

50 Years - 95 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Dementia, either sex, age 50-95 years
Probable Alzheimer's disease
Intellectual impairment present for at least 6 months
Mini Mental State Exam (MMSE) score of 5-26 for outpatients and 2-26 for nursing home patients
Availability of informant who has had direct contact with the patient for an average of at least once every week during the 3 months prior to study entry
Meets Neuropsychiatric Inventory (NPI) criteria for either (1) psychosis, or (2) agitation/aggression
Able to mobilize independently (if wheelchair-bound, the patient must be able to self-propel)
Free of psychotropic medication (or able to tolerate washout) for at least 1 week prior to study entry. Low dose antidepressants and sedative/hypnotics allowed if they cannot be washed out and the dose remains stable for the study duration
Expected to complete the study (including all efficacy evaluations) and be without major sensory impairment that would prevent participation in any aspect of the study

Exclusion Criteria:

Current primary Axis I psychiatric disorder other than AD
Substance abuse or dependence currently, or within the past year
Dementia due to head trauma
History of allergy to risperidone or intolerance to risperidone
Diffuse Lewy body disease
History of seizure disorder, infectious encephalitis, Parkinson's disease, central nervous system (CNS) neoplasm, tardive dyskinesia, stroke, transient ischemic attack (TIA) or uncontrolled atrial fibrillation
Use of monoamine oxidase inhibitors (MAOIs) and unable to undergo 3-week washout; patients also may not take MAOIs for 2 weeks after completing the study
In treatment with (a) depot antipsychotic within 2 weeks of the screening visit
Untreated or incompletely treated hypothyroidism
Active, unstable medical condition that requires active medication adjustment or surgery
Need for electroconvulsive treatment (ECT)
Significant risk for harm to themselves or others as a result of randomization to placebo
History of malignant neoplasm during the last 5 years

Sites / Locations

Tuscaloosa VA Medical Center, Department of Psychiatry
WLA VA Medical Center/UCLA, Psychiatry
Research Center for Clinical Studies, Inc.
University of Iowa College of Medicine
Mount Sinai School of Medicine, Alzheimer's Disease Research Center
New York State Psychiatric Institute, Columbia University
Medical University of South Carolina

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Other

Arm Label

Risperidone-risperidone

Risperidone-Placebo

Placebo-Placebo

Arm Description

Risperidone for 16 weeks followed by risperidone for 16 weeks

Risperidone for 16 weeks followed by placebo for 16 weeks

Placebo for 16 weeks followed by placebo for 16 weeks

Outcomes

Primary Outcome Measures

Relapse by Study Week 32

A relapse occurred in Phase B (post-randomization) if both of the following criteria were met: Increase in the Neuropsychiatric Inventory (NPI) core score of 30% or more OR a 5-point increase from the baseline NPI score at the end of Phase A A score of 6 (much worse) or 7 (very much worse) on the Clinical Global Impression-Change (CGI-C) at any visit.

Secondary Outcome Measures

Relapse by Study Week 48

Same definition and criteria as the primary outcome

Mini Mental State Exam (MMSE)

The MMSE assesses cognition. Scores range from 0-30, with higher scores indicating better cognition. For each subject, the change in MMSE between week 16 and baseline (randomization) was calculated by subtraction, so that a positive value indicates an increase in MMSE over time.

Treatment Emergent Symptoms Scale (TESS)

The Treatment Emergent Symptom Scale (TESS) assesses 26 somatic symptoms. Total scores range from 0-26, with a score of 0 or 1 for each item. Higher scores indicate more somatic symptoms. For each subject, the change in TESS between week 16 and baseline (randomization) was calculated by subtraction, so that a positive value indicates an increase in TESS over time.

Extrapyramidal Signs (EPS)

Extrapyramidal signs, also known as Parkinsonian signs, refer to signs of tremor, rigidity, and bradykinesia (slowed movement) that are seen in Parkinson's disease. Assessment of extrapyramidal signs (EPS) were made with the use of the Simpson-Angus scale (which ranges from 1-40) with higher scores indicating more extrapyramidal signs. For each subject, the change in EPS between week 16 and baseline (randomization) was calculated by subtraction, so that a positive value indicates an increase in EPS over time.

AIMS

The Abnormal Involuntary Movement Scale (AIMS) assesses signs of tardive dyskinesia, a movement disorder that can occur with prolonged use of antipsychotic medication. The AIMS score ranges from 0 to 35, with higher scores indicating more severe symptoms. For each subject, the change in AIMS score between week 16 and randomization was calculated by subtraction, so that a positive value indicates an increase in AIMS over time.

Physical Self-Maintenance Scale (PSMS)

Physical Self-Maintenance Scale, which ranges from 1 to 30, with higher scores indicating WORSE functioning. For each subject, the change in PSMS between week 16 and randomization was calculated by subtraction, so that a positive value indicates an increase in PSMS (worse functioning) over time.

Weight

For each subject, the change in weight in pounds between week 16 and randomization was calculated by subtraction, so that a positive value indicates an increase in weight over time.

Full Information

NCT ID

NCT00417482

First Posted

December 28, 2006

Last Updated

March 14, 2013

Sponsor

New York State Psychiatric Institute

Collaborators

National Institute on Aging (NIA), Columbia University

1. Study Identification

Unique Protocol Identification Number

NCT00417482

Brief Title

Antipsychotic Discontinuation in Alzheimer's Disease

Acronym

ADAD

Official Title

Antipsychotic Discontinuation in Alzheimer's Disease

Study Type

Interventional

2. Study Status

Record Verification Date

March 2013

Overall Recruitment Status

Completed

Study Start Date

August 2004 (undefined)

Primary Completion Date

April 2011 (Actual)

Study Completion Date

April 2011 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

New York State Psychiatric Institute

Collaborators

National Institute on Aging (NIA), Columbia University

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

In patients with Alzheimer's disease (AD) who respond to antipsychotic treatment of psychosis and/or agitation/aggression, the relapse risk after discontinuation is not established. AD patients with psychosis and/or agitation/aggression receive 16 weeks of open risperidone treatment (Phase A). Responders are then randomized, double-blind, to one of three arms in Phase B: (1) continuation risperidone for 32 weeks, (2) risperidone for 16 weeks followed by placebo for 16 weeks, (3) placebo for 32 weeks. The primary outcome is time to relapse of psychosis/agitation.

Detailed Description

This multicenter study (6 academic sites and 2 non-academic sites) involves treating AD patients (assisted living or nursing home patients, and outpatients) using an atypical antipsychotic, risperidone. In Phase A, 180 AD patients with psychosis and/or agitation/aggression receive open treatment with risperidone for 16 weeks. Responders are randomized, double-blind, to one of three arms in Phase B: (1) continuation risperidone for the next 32 weeks, (2) risperidone for the next 16 weeks followed by placebo for 16 weeks, or (3) placebo for the next 32 weeks. The primary hypothesis is that in the first 16 weeks of Phase B, relapse risk will be lower with continuation risperidone (Arms 1 + 2) compared to discontinuation on placebo (Arm 3). The secondary hypothesis is that in the second 16 weeks of Phase B, relapse risk will be lower with continuation risperidone (Arm 1) compared to discontinuation on placebo (Arm 2). For both randomized time periods, the proportions who relapse will be compared for interpretive support. This design provides useful data on the efficacy and side effects of longer term treatment with risperidone, and, in particular, critical information about the time to relapse and likelihood of relapse in patients switched from risperidone to placebo. This information is essential to guide the clinician toward optimal use of such medications in one of the most challenging types of patients: the AD patient with psychosis and/or agitation/aggression. The results of this study will also help to address Federal regulations urging early antipsychotic discontinuation in nursing homes.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Alzheimer Disease, Psychotic Disorders, Agitation, Aggression

Keywords

Risperidone treatment, psychosis, agitation, aggression,, discontinuation, placebo

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 4

Interventional Study Model

Parallel Assignment

Masking

ParticipantCare ProviderInvestigatorOutcomes Assessor

Allocation

Randomized

Enrollment

180 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Risperidone-risperidone

Arm Type

Other

Arm Description

Risperidone for 16 weeks followed by risperidone for 16 weeks

Arm Title

Risperidone-Placebo

Arm Type

Other

Arm Description

Risperidone for 16 weeks followed by placebo for 16 weeks

Arm Title

Placebo-Placebo

Arm Type

Other

Arm Description

Placebo for 16 weeks followed by placebo for 16 weeks

Intervention Type

Drug

Intervention Name(s)

risperidone

Other Intervention Name(s)

Risperdal

Intervention Description

Risperidone open label flexible dose 0.25 to 3 mg daily for first 16 weeks; dose at 16 weeks then fixed for randomized trial

Primary Outcome Measure Information:

Title

Relapse by Study Week 32

Description

A relapse occurred in Phase B (post-randomization) if both of the following criteria were met: Increase in the Neuropsychiatric Inventory (NPI) core score of 30% or more OR a 5-point increase from the baseline NPI score at the end of Phase A A score of 6 (much worse) or 7 (very much worse) on the Clinical Global Impression-Change (CGI-C) at any visit.

Time Frame

0-16 weeks in Phase B (16-32 weeks in study)

Secondary Outcome Measure Information:

Title

Relapse by Study Week 48

Description

Same definition and criteria as the primary outcome

Time Frame

16-32 weeks in Phase B (32-48 weeks in study)

Title

Mini Mental State Exam (MMSE)

Description

The MMSE assesses cognition. Scores range from 0-30, with higher scores indicating better cognition. For each subject, the change in MMSE between week 16 and baseline (randomization) was calculated by subtraction, so that a positive value indicates an increase in MMSE over time.

Time Frame