Antipsychotic Discontinuation in Alzheimer's Disease (ADAD)
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ClinicalTrials.gov Identifier: NCT00417482 |
Recruitment Status
:
Completed
First Posted
: January 1, 2007
Results First Posted
: April 24, 2013
Last Update Posted
: April 24, 2013
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Condition or disease | Intervention/treatment | Phase |
---|---|---|
Alzheimer Disease Psychotic Disorders Agitation Aggression | Drug: risperidone | Phase 4 |
Study Type : | Interventional (Clinical Trial) |
Actual Enrollment : | 180 participants |
Allocation: | Randomized |
Intervention Model: | Parallel Assignment |
Masking: | Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor) |
Primary Purpose: | Treatment |
Official Title: | Antipsychotic Discontinuation in Alzheimer's Disease |
Study Start Date : | August 2004 |
Actual Primary Completion Date : | April 2011 |
Actual Study Completion Date : | April 2011 |

Arm | Intervention/treatment |
---|---|
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
|
- Relapse by Study Week 32 [ Time Frame: 0-16 weeks in Phase B (16-32 weeks in study) ]
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.
- Relapse by Study Week 48 [ Time Frame: 16-32 weeks in Phase B (32-48 weeks in study) ]Same definition and criteria as the primary outcome
- Mini Mental State Exam (MMSE) [ Time Frame: Phase B, weeks 1-16 (study weeks 16-32) ]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) ]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) ]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) ]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) ]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) ]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.

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Ages Eligible for Study: | 50 Years to 95 Years (Adult, Senior) |
Sexes Eligible for Study: | All |
Accepts Healthy Volunteers: | No |
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

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00417482
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 |
Principal Investigator: | Davangere P. Devanand, MD | NYSPI/Columbia University |
Additional Information:
Publications of Results:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: | New York State Psychiatric Institute |
ClinicalTrials.gov Identifier: | NCT00417482 History of Changes |
Other Study ID Numbers: |
#5598R 5R01AG021488 ( U.S. NIH Grant/Contract ) |
First Posted: | January 1, 2007 Key Record Dates |
Results First Posted: | April 24, 2013 |
Last Update Posted: | April 24, 2013 |
Last Verified: | March 2013 |
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 |