Antipsychotic Discontinuation in Alzheimer's Disease
ADAD
2 other identifiers
interventional
180
1 country
7
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_4 alzheimer-disease
Started Aug 2004
Longer than P75 for phase_4 alzheimer-disease
7 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
Study Start
First participant enrolled
August 1, 2004
CompletedFirst Submitted
Initial submission to the registry
December 28, 2006
CompletedFirst Posted
Study publicly available on registry
January 1, 2007
CompletedPrimary Completion
Last participant's last visit for primary outcome
April 1, 2011
CompletedStudy Completion
Last participant's last visit for all outcomes
April 1, 2011
CompletedResults Posted
Study results publicly available
April 24, 2013
CompletedApril 24, 2013
March 1, 2013
6.7 years
December 28, 2006
February 11, 2013
March 14, 2013
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Relapse by Study Week 32
A relapse occurred in Phase B (post-randomization) if both of the following criteria were met: 1. 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 2. A score of 6 (much worse) or 7 (very much worse) on the Clinical Global Impression-Change (CGI-C) at any visit.
0-16 weeks in Phase B (16-32 weeks in study)
Secondary Outcomes (7)
Relapse by Study Week 48
16-32 weeks in Phase B (32-48 weeks in study)
Mini Mental State Exam (MMSE)
Phase B, weeks 1-16 (study weeks 16-32)
Treatment Emergent Symptoms Scale (TESS)
Phase B, weeks 1-16 (study weeks 16-32)
Extrapyramidal Signs (EPS)
Phase B, weeks 1-16 (study weeks 16-32)
AIMS
Phase B, weeks 1-16 (study weeks 16-32)
- +2 more secondary outcomes
Study Arms (3)
Risperidone-risperidone
OTHERRisperidone for 16 weeks followed by risperidone for 16 weeks
Risperidone-Placebo
OTHERRisperidone for 16 weeks followed by placebo for 16 weeks
Placebo-Placebo
OTHERPlacebo for 16 weeks followed by placebo for 16 weeks
Interventions
Risperidone open label flexible dose 0.25 to 3 mg daily for first 16 weeks; dose at 16 weeks then fixed for randomized trial
Eligibility Criteria
You may qualify if:
- 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
You may not qualify if:
- 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
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- New York State Psychiatric Institutelead
- National Institute on Aging (NIA)collaborator
- Columbia Universitycollaborator
Study Sites (7)
Tuscaloosa VA Medical Center, Department of Psychiatry
Tuscaloosa, Alabama, 35404, United States
WLA VA Medical Center/UCLA, Psychiatry
Los Angeles, California, 90073, United States
Research Center for Clinical Studies, Inc.
Norwalk, Connecticut, 06851, United States
University of Iowa College of Medicine
Iowa City, Iowa, 52242, United States
Mount Sinai School of Medicine, Alzheimer's Disease Research Center
New York, New York, 10029, United States
New York State Psychiatric Institute, Columbia University
New York, New York, 10032, United States
Medical University of South Carolina
North Charleston, South Carolina, 29406, United States
Related Publications (2)
Devanand DP, Mintzer J, Schultz SK, Andrews HF, Sultzer DL, de la Pena D, Gupta S, Colon S, Schimming C, Pelton GH, Levin B. Relapse risk after discontinuation of risperidone in Alzheimer's disease. N Engl J Med. 2012 Oct 18;367(16):1497-507. doi: 10.1056/NEJMoa1114058.
PMID: 23075176RESULTPatel AN, Lee S, Andrews HF, Pelton GH, Schultz SK, Sultzer DL, Mintzer J, de la Pena D, Gupta S, Colon S, Schimming C, Levin B, Devanand DP. Prediction of Relapse After Discontinuation of Antipsychotic Treatment in Alzheimer's Disease: The Role of Hallucinations. Am J Psychiatry. 2017 Apr 1;174(4):362-369. doi: 10.1176/appi.ajp.2016.16020226. Epub 2016 Nov 18.
PMID: 27855483DERIVED
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Limitations and Caveats
Comparisons of adverse events in Phase B were limited by the small sample \& the truncated observation period for relapsed subjects. Identification of predictors of relapse after discontinuation of treatment was limited by the small sample.
Results Point of Contact
- Title
- Davangere P. Devanand, MD
- Organization
- New York State Psychiatric Institute
Study Officials
- PRINCIPAL INVESTIGATOR
Davangere P. Devanand, MD
NYSPI/Columbia University
Publication Agreements
- PI is Sponsor Employee
- No
- Restrictive Agreement
- No
Study Design
- Study Type
- interventional
- Phase
- phase 4
- Allocation
- RANDOMIZED
- Masking
- QUADRUPLE
- Who Masked
- PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
December 28, 2006
First Posted
January 1, 2007
Study Start
August 1, 2004
Primary Completion
April 1, 2011
Study Completion
April 1, 2011
Last Updated
April 24, 2013
Results First Posted
April 24, 2013
Record last verified: 2013-03