Antipsychotic Discontinuation in Alzheimer's Disease (ADAD)

This study has been completed.
Sponsor:
Collaborators:
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
Results First Received: February 11, 2013  
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
Conditions: Alzheimer Disease
Psychotic Disorders
Agitation
Aggression
Intervention: Drug: risperidone

  Participant Flow
  Hide Participant Flow

Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
Patients were recruited from memory clinics including Alzheimer Research Centers, geriatric psychiatry clinics, VA clinics, physician referrals and advertising.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment

180 Patients with Alzheimer's disease (AD) & psychosis or agitation-aggression received open treatment with risperidone for 16 weeks in Phase A. Of 180 patients, 112 were responders and 110 were randomized in Phase B.

Phase B: 110 responders were randomized, double-blind, to one of three arms in Phase B.


Reporting Groups
  Description
Arm 1: Risperidone-Risperidone

Phase A involved open flexible dose risperidone treatment for 16 weeks. At 16 weeks, non-responders exited the study. Responders were randomized, double-blind, to one of three arms in Phase B: (1) continuation risperidone for 32 weeks (Arm 1), (2) risperidone for 16 weeks followed by placebo for 16 weeks (Arm 2), (3) placebo for 32 weeks (Arm 3).

Phase B Arm 1: Risperidone for 16 weeks followed by risperidone for 16 weeks; Risperidone open label flexible dose was administered at a dose of 0.25 to 3 mg daily for first 16 weeks; dose at 16 weeks then fixed for the randomized trial

Phase B Arm 2: Risperidone-Placebo

Phase A involved open flexible dose risperidone treatment for 16 weeks. At 16 weeks, non-responders exited the study. Responders were randomized, double-blind, to one of three arms in Phase B: (1) continuation risperidone for 32 weeks (Arm 1), (2) risperidone for 16 weeks followed by placebo for 16 weeks (Arm 2), (3) placebo for 32 weeks (Arm 3).

Phase B Arm 2: Risperidone for 16 weeks followed by placebo for 16 weeks;

Phase B Arm 3: Placebo-Placebo

Phase A involved open flexible dose risperidone treatment for 16 weeks. At 16 weeks, non-responders exited the study. Responders were randomized, double-blind, to one of three arms in Phase B: (1) continuation risperidone for 32 weeks (Arm 1), (2) risperidone for 16 weeks followed by placebo for 16 weeks (Arm 2), (3) placebo for 32 weeks (Arm 3).

Phase B Arm 3: Patients were randomized to placebo for 32 weeks.


Participant Flow for 2 periods

Period 1:   Phase B 1st 16 Weeks
    Arm 1: Risperidone-Risperidone     Phase B Arm 2: Risperidone-Placebo     Phase B Arm 3: Placebo-Placebo  
STARTED     32 [1]   38 [1]   40 [2]
COMPLETED     13     27     13  
NOT COMPLETED     19     11     27  
Lack of Efficacy                 14                 8                 24  
Adverse Event                 2                 0                 1  
Moved, Unclear reasons                 2                 3                 2  
Death                 1                 0                 0  
[1] Risperidone 16 weeks.
[2] Placebo 16 weeks.

Period 2:   Phase B 2nd 16 Weeks
    Arm 1: Risperidone-Risperidone     Phase B Arm 2: Risperidone-Placebo     Phase B Arm 3: Placebo-Placebo  
STARTED     13 [1]   27 [2]   13 [2]
COMPLETED     10     14     10  
NOT COMPLETED     3     13     3  
Lack of Efficacy                 1                 12                 2  
Adverse Event                 0                 0                 1  
Moved; unclear reason                 1                 0                 0  
Death                 1                 1                 0  
[1] Risperidone for 16 weeks.
[2] Placebo for 16 weeks.



  Baseline Characteristics


  Outcome Measures
  Show All Outcome Measures

1.  Primary:   Relapse by Study Week 32   [ Time Frame: 0-16 weeks in Phase B (16-32 weeks in study) ]

2.  Secondary:   Relapse by Study Week 48   [ Time Frame: 16-32 weeks in Phase B (32-48 weeks in study) ]

3.  Secondary:   Mini Mental State Exam (MMSE)   [ Time Frame: Phase B, weeks 1-16 (study weeks 16-32) ]

4.  Secondary:   Treatment Emergent Symptoms Scale (TESS)   [ Time Frame: Phase B, weeks 1-16 (study weeks 16-32) ]

5.  Secondary:   Extrapyramidal Signs (EPS)   [ Time Frame: Phase B, weeks 1-16 (study weeks 16-32) ]

6.  Secondary:   AIMS   [ Time Frame: Phase B, weeks 1-16 (study weeks 16-32) ]

7.  Secondary:   Physical Self-Maintenance Scale (PSMS)   [ Time Frame: Phase B, weeks 1-16 (study weeks 16-32) ]

8.  Secondary:   Weight   [ Time Frame: Phase B, weeks 1-16 (study weeks 16-32) ]


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
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Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
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.


  More Information