Antipsychotic Discontinuation in Alzheimer's Disease (ADAD)
This study has been completed.
Sponsor:
New York State Psychiatric Institute
Collaborators:
National Institute on Aging (NIA)
Columbia University
Information provided by (Responsible Party):
New York State Psychiatric Institute
ClinicalTrials.gov Identifier:
NCT00417482
First received: December 28, 2006
Last updated: March 14, 2013
Last verified: March 2013
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Purpose
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.
| Condition | Intervention | Phase |
|---|---|---|
|
Alzheimer Disease Psychotic Disorders Agitation Aggression |
Drug: risperidone |
Phase 4 |
| Study Type: | Interventional |
| 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: | Antipsychotic Discontinuation in Alzheimer's Disease |
Resource links provided by NLM:
Further study details as provided by New York State Psychiatric Institute:
Primary Outcome Measures:
- Relapse by Study Week 32 [ Time Frame: 0-16 weeks in Phase B (16-32 weeks in study) ] [ Designated as safety issue: No ]
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 [ Time Frame: 16-32 weeks in Phase B (32-48 weeks in study) ] [ Designated as safety issue: No ]Same definition and criteria as the primary outcome
- Mini Mental State Exam (MMSE) [ Time Frame: Phase B, weeks 1-16 (study weeks 16-32) ] [ Designated as safety issue: Yes ]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) [ Time Frame: Phase B, weeks 1-16 (study weeks 16-32) ] [ Designated as safety issue: Yes ]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) [ Time Frame: Phase B, weeks 1-16 (study weeks 16-32) ] [ Designated as safety issue: Yes ]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 [ Time Frame: Phase B, weeks 1-16 (study weeks 16-32) ] [ Designated as safety issue: Yes ]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) [ Time Frame: Phase B, weeks 1-16 (study weeks 16-32) ] [ Designated as safety issue: Yes ]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 [ Time Frame: Phase B, weeks 1-16 (study weeks 16-32) ] [ Designated as safety issue: Yes ]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.
| Enrollment: | 180 |
| Study Start Date: | August 2004 |
| Study Completion Date: | April 2011 |
| Primary Completion Date: | April 2011 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
|
Risperidone-risperidone
Risperidone for 16 weeks followed by risperidone for 16 weeks
|
Drug: risperidone
Risperidone open label flexible dose 0.25 to 3 mg daily for first 16 weeks; dose at 16 weeks then fixed for randomized trial
Other Name: Risperdal
|
|
Risperidone-Placebo
Risperidone for 16 weeks followed by placebo for 16 weeks
|
Drug: risperidone
Risperidone open label flexible dose 0.25 to 3 mg daily for first 16 weeks; dose at 16 weeks then fixed for randomized trial
Other Name: Risperdal
|
|
Placebo-Placebo
Placebo for 16 weeks followed by placebo for 16 weeks
|
Drug: risperidone
Risperidone open label flexible dose 0.25 to 3 mg daily for first 16 weeks; dose at 16 weeks then fixed for randomized trial
Other Name: Risperdal
|
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.
Eligibility| Ages Eligible for Study: | 50 Years to 95 Years (Adult, Senior) |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
Criteria
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
Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study.
To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below.
For general information, see Learn About Clinical Studies.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00417482
Please refer to this study by its ClinicalTrials.gov identifier: NCT00417482
Locations
| United States, Alabama | |
| Tuscaloosa VA Medical Center, Department of Psychiatry | |
| Tuscaloosa, Alabama, United States, 35404 | |
| United States, California | |
| WLA VA Medical Center/UCLA, Psychiatry | |
| Los Angeles, California, United States, 90073 | |
| United States, Connecticut | |
| Research Center for Clinical Studies, Inc. | |
| Norwalk, Connecticut, United States, 06851 | |
| United States, Iowa | |
| University of Iowa College of Medicine | |
| Iowa City, Iowa, United States, 52242 | |
| United States, New York | |
| Mount Sinai School of Medicine, Alzheimer's Disease Research Center | |
| New York, New York, United States, 10029 | |
| New York State Psychiatric Institute, Columbia University | |
| New York, New York, United States, 10032 | |
| United States, South Carolina | |
| Medical University of South Carolina | |
| North Charleston, South Carolina, United States, 29406 | |
Sponsors and Collaborators
New York State Psychiatric Institute
National Institute on Aging (NIA)
Columbia University
Investigators
| Principal Investigator: | Davangere P. Devanand, MD | NYSPI/Columbia University |
More Information
Additional Information:
Publications:
| Responsible Party: | New York State Psychiatric Institute |
| ClinicalTrials.gov Identifier: | NCT00417482 History of Changes |
| Other Study ID Numbers: | #5598R 5R01AG021488 |
| Study First Received: | December 28, 2006 |
| Results First Received: | February 11, 2013 |
| Last Updated: | March 14, 2013 |
| Health Authority: | United States: Institutional Review Board |
Keywords provided by New York State Psychiatric Institute:
|
Risperidone treatment, psychosis, agitation, aggression, discontinuation, placebo |
Additional relevant MeSH terms:
|
Alzheimer Disease Psychomotor Agitation Psychotic Disorders Mental Disorders Aggression Dementia Brain Diseases Central Nervous System Diseases Nervous System Diseases Tauopathies Neurodegenerative Diseases Neurocognitive Disorders Dyskinesias Neurologic Manifestations Psychomotor Disorders |
Neurobehavioral Manifestations Signs and Symptoms Schizophrenia Spectrum and Other Psychotic Disorders Behavioral Symptoms Risperidone Antipsychotic Agents Serotonin Antagonists Serotonin Agents Neurotransmitter Agents Molecular Mechanisms of Pharmacological Action Physiological Effects of Drugs Tranquilizing Agents Central Nervous System Depressants Psychotropic Drugs Dopamine Antagonists |
ClinicalTrials.gov processed this record on September 29, 2016