The CATIE Alzheimer's Disease Trial is part of the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) Project. The study is for people with Alzheimer's disease who are having trouble with their thinking or behavior. In particular, this study is trying to find out the best treatment for people who have hallucinations (seeing or hearing things that aren't there), delusions (false beliefs), or agitation. The design of the trial helps to increase the chance that participants in the study receive a medication that helps them. The study uses three medications known as atypical antipsychotics (olanzapine, quetiapine, risperidone), which are the newest medications that are currently available for treating these problems. Participants may also receive an antidepressant (citalopram). The trial lasts for 36 weeks. Participants are given a thorough evaluation at no cost to ensure that this study is appropriate. In addition, the caregiver, family member, or friend who comes with the participant will be offered an educational program about Alzheimer's disease.

Condition	Treatment or Intervention
Alzheimer's Disease	Drug: Olanzapine  Drug: Quetiapine  Drug: Risperidone  Drug: Citalopram

Further Study Details: 

Expected Total Enrollment:  450

There are four phases.

Phase I: In the initial treatment phase (Phase 1), patients will be randomized to one of the three atypical antipsychotics or placebo in the ratio 100:100:100:150 respectively. After two weeks, the investigator can move the patient to the next phase because of lack of efficacy or tolerability. At week 12, the investigator can decide whether the current medication is sufficiently optimal or it would be more beneficial to try another randomized medication.

Phase 2: Phase 2 starts when the patient is randomized to a second medication, i.e., olanzapine, quetiapine, risperidone, or citalopram. Patients will be randomized from an antipsychotic treatment to another antipsychotic treatment or citalopram in the ratio 3:3:2, or from placebo to an antipsychotic treatment or citalopram in the ratio 1:1:1:3 respectively. Therefore, 50% of patients who took placebo in Phase 1 will be randomized to an antipsychotic in Phase 2, and 50% will be randomized to citalopram in Phase 2. After the initial two weeks in Phase 2, the investigator can move the patient to the next phase, due to lack of efficacy or tolerability. After the patient has been on the Phase 2 study drug for approximately 12 weeks, the investigator can decide whether the current medication is sufficiently optimal or whether it would be more beneficial to try another randomized medication.

Phase 3: Phase 3 is randomized open-label treatment of one of the medications not previously received, i.e., olanzapine, quetiapine, risperidone, or citalopram. Treatment failures to the second treatment can be switched to a third open-label treatment. During Phase 3 patients will be maintained on their treatments openly and managed clinically until week 36.

If the investigator determines that the patient's response is not sufficiently optimal to the randomized open-label medication, then after the first two weeks of Phase 3, the investigator can prescribe another medication (of the investigator's choice) to the patient. If this occurs then patients are classed as being in the Open-Choice Phase.

Open-Choice Phase: The Open-Choice Phase can be entered at anytime during the 36-week study and directly from any of the three phases. There are four reasons a patient can enter the open choice phase: -Withdrawal from Phase 1 or Phase 2 with the patient or surrogate decision-maker refusing to proceed to the next randomized phase; -Withdrawal from Phase 3; -Withdrawal from current study drug from any of the three previous phases due to antipsychotic medication no longer being required in the opinion of the investigator; or -Withdrawal due to concomitant treatment with an exclusionary medication.

The Open-Choice Phase is designed to keep patients monitored in the trial for the 36-week duration.

Genders Eligible for Study:  Both

Criteria

Inclusion Criteria:

• Diagnosis of Dementia of the Alzheimer's Type
• Ambulatory, Outpatients who have an informant living/visiting at least 8 hours/week over 3-4 days.
• Presence of delusions, hallucinations, agitation impacting functioning and requiring medication treatment
• Agitation or psychotic symptoms began after signs or symptoms of dementia

Exclusion (prospective participants must not:)

• Be benefiting from psychotropic medication, antidepressants or anticonvulsants
• Be diagnosed with schizophrenia, schizoaffective disorder, delusional disorder or mood disorder with psychotic features.
• Have severe or unstable medical illness requiring active treatment
• Have hypersensitivity or intolerance of any of the study medications

Alabama
      Tuscaloosa VA Medical Center, Tuscaloosa,  Alabama,  35404,  United States
California
      University of California, Los Angeles, VA Medical Center, Los Angeles,  California,  90073,  United States
      University of California-San Diego, VA Medical Center, San Diego,  California,  92161,  United States
      University of Southern California Dept of Psychiatry& Behavioral Sciences, Los Angeles,  California,  90033,  United States
      Stanford University School of Medicine, Stanford,  California,  94305,  United States
      University of California, Irvine Medical Center, Irvine,  California,  92697,  United States
Connecticut
      Yale University School of Medicine, New Haven,  Connecticut,  06510,  United States
Florida
      University of South Florida Suncoast Gerontology Center, Tampa,  Florida,  33617,  United States
      Palm Beach Neurology/Premiere Research Institute, West Palm Beach,  Florida,  33407,  United States
      Mental Health Advocates, Inc., Boca Raton,  Florida,  33432,  United States
      Berma Research Group, Hialeah,  Florida,  33016,  United States
Georgia
      Emory University - Wesley Woods Health Center, Atlanta,  Georgia,  30329,  United States
Hawaii
      University of Hawaii, Honolulu,  Hawaii,  96813,  United States
Illinois
      Southern Illinois School of Medicine, Springfield,  Illinois,  62702,  United States
      Northwestern University Medical School, Chicago,  Illinois,  60611,  United States
Iowa
      University of Iowa College of Medicine, Iowa City,  Iowa,  52242,  United States
Louisiana
      Louisiana State University Health Sciences Center, Shreveport,  Louisiana,  71103,  United States
Maryland
      Johns Hopkins University, Baltimore,  Maryland,  21287,  United States
Missouri
      Millennium Psychiatric Associates, St. Louis,  Missouri,  63044,  United States
New Jersey
      University of Medicine and Dentistry of New Jersey, Piscataway,  New Jersey,  08855-1382,  United States
      University of Medicine and Dentistry of New Jersey-Stratford, Stratford,  New Jersey,  08084,  United States
New York
      Staten Island University Hospital, Staten Island,  New York,  10305,  United States
      Monroe Community Hospital, Rochester,  New York,  14620,  United States
      Columbia University, New York,  New York,  10032,  United States
      Mount Sinai School of Medicine, New York,  New York,  10029,  United States
      Global Research and Consulting, Olean,  New York,  14760,  United States
North Carolina
      Duke University Medical Center, Durham,  North Carolina,  27710,  United States
      Wake Forest University School of Medicine, Winston Salem,  North Carolina,  27157,  United States
Ohio
      University Hospital Health Systems-Laurelwood Hospital, Willoughby,  Ohio,  44904,  United States
Pennsylvania
      Mental Illness Research Education and Clinical Center, Philadelphia,  Pennsylvania,  19104,  United States
      VA Medical Center, Coatesville,  Pennsylvania,  19320,  United States
South Carolina
      Medical University of South Carolina, North Charleston,  South Carolina,  29406,  United States
Texas
      University of Texas Southwestern Medical Center, Dallas,  Texas,  75235-9070,  United States
Vermont
      Southwestern Vermont Medical Center- The Memory Clinic, Bennington,  Vermont,  05201,  United States

Study chairs or principal investigators

Lon Schneider, MD,  Principal Investigator,  University of Southern California   
Pierre Tariot, MD,  Principal Investigator,  University of Rochester   

Study ID Numbers:  N01MH90001-AD
Record last reviewed:  November 2004
Last Updated:  November 9, 2004
Record first received:  April 20, 2001
ClinicalTrials.gov Identifier:  NCT00015548
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08