Clinical trial NCT00015548: CATIE-Alzheimer's Disease Trial
Official title: Comparative Effectiveness of Antipsychotic Medications in Patients With Alzheimer's Disease (CATIE Alzheimer's Disease Trial)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Alzheimer's Disease
Keywords: antipsychotic treatment
Alzheimer's disease
agitation
dementia
psychosis
behavioral symptoms
hallucinations
delusions
Lead sponsor: National Institute of Mental Health (NIMH)
Sponsor class: NIH
First posted: 2001-04-23
Enrollment: 450
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

Detailed description: 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.

Eligibility 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

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
city: Tuscaloosa
country: United States
facility: Tuscaloosa VA Medical Center
state: Alabama
city: Irvine
country: United States
facility: University of California, Irvine Medical Center
state: California
city: Los Angeles
country: United States
facility: University of Southern California Dept of Psychiatry& Behavioral Sciences
state: California
city: Los Angeles
country: United States
facility: University of California, Los Angeles, VA Medical Center
state: California
city: San Diego
country: United States
facility: University of California-San Diego, VA Medical Center
state: California
city: Stanford
country: United States
facility: Stanford University School of Medicine
state: California
city: New Haven
country: United States
facility: Yale University School of Medicine
state: Connecticut
city: Boca Raton
country: United States
facility: Mental Health Advocates, Inc.
state: Florida
city: Hialeah
country: United States
facility: Berma Research Group
state: Florida
city: Tampa
country: United States
facility: University of South Florida Suncoast Gerontology Center
state: Florida
city: West Palm Beach
country: United States
facility: Palm Beach Neurology/Premiere Research Institute
state: Florida
city: Atlanta
country: United States
facility: Emory University - Wesley Woods Health Center
state: Georgia
city: Honolulu
country: United States
facility: University of Hawaii
state: Hawaii
city: Chicago
country: United States
facility: Northwestern University Medical School
state: Illinois
city: Springfield
country: United States
facility: Southern Illinois School of Medicine
state: Illinois
city: Iowa City
country: United States
facility: University of Iowa College of Medicine
state: Iowa
city: Shreveport
country: United States
facility: Louisiana State University Health Sciences Center
state: Louisiana
city: Baltimore
country: United States
facility: Johns Hopkins University
state: Maryland
city: St. Louis
country: United States
facility: Millennium Psychiatric Associates
state: Missouri
city: Piscataway
country: United States
facility: University of Medicine and Dentistry of New Jersey
state: New Jersey
city: Stratford
country: United States
facility: University of Medicine and Dentistry of New Jersey-Stratford
state: New Jersey
city: New York
country: United States
facility: Mount Sinai School of Medicine
state: New York
city: New York
country: United States
facility: Columbia University
state: New York
city: Olean
country: United States
facility: Global Research and Consulting
state: New York
city: Rochester
country: United States
facility: Monroe Community Hospital
state: New York
city: Staten Island
country: United States
facility: Staten Island University Hospital
state: New York
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
city: Winston Salem
country: United States
facility: Wake Forest University School of Medicine
state: North Carolina
city: Willoughby
country: United States
facility: University Hospital Health Systems-Laurelwood Hospital
state: Ohio
city: Coatesville
country: United States
facility: VA Medical Center
state: Pennsylvania
city: Philadelphia
country: United States
facility: Mental Illness Research Education and Clinical Center
state: Pennsylvania
city: North Charleston
country: United States
facility: Medical University of South Carolina
state: South Carolina
city: Dallas
country: United States
facility: University of Texas Southwestern Medical Center
state: Texas
city: Bennington
country: United States
facility: Southwestern Vermont Medical Center- The Memory Clinic
state: Vermont
Study officials:
affiliation: University of Southern California
name: Lon Schneider, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Rochester
name: Pierre Tariot, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Schneider LS, Tariot PN, Lyketsos CG, Dagerman KS, Davis KL, Davis S, Hsiao JK, Jeste DV, Katz IR, Olin JT, Pollock BG, Rabins PV, Rosenheck RA, Small GW, Lebowitz B, Lieberman JA. National Institute of Mental Health Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE): Alzheimer disease trial methodology. Am J Geriatr Psychiatry. 2001 Fall;9(4):346-60.
citation: Schneider LS, Ismail MS, Dagerman K, Davis S, Olin J, McManus D, Pfeiffer E, Ryan JM, Sultzer DL, Tariot PN. Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE): Alzheimer's disease trial. Schizophr Bull. 2003;29(1):57-72. doi: 10.1093/oxfordjournals.schbul.a006991.
citation: Schneider LS, Tariot PN, Dagerman KS, Davis SM, Hsiao JK, Ismail MS, Lebowitz BD, Lyketsos CG, Ryan JM, Stroup TS, Sultzer DL, Weintraub D, Lieberman JA; CATIE-AD Study Group. Effectiveness of atypical antipsychotic drugs in patients with Alzheimer's disease. N Engl J Med. 2006 Oct 12;355(15):1525-38. doi: 10.1056/NEJMoa061240.
citation: Reeves S, Bertrand J, Uchida H, Yoshida K, Otani Y, Ozer M, Liu KY, Bramon E, Bies R, Pollock BG, Howard R. Towards safer risperidone prescribing in Alzheimer's disease. Br J Psychiatry. 2021 May;218(5):268-275. doi: 10.1192/bjp.2020.225.
citation: Nagata T, Shinagawa S, Yoshida K, Noda Y, Shigeta M, Mimura M, Nakajima S. Early Improvements of Individual Symptoms With Antipsychotics Predict Subsequent Treatment Response of Neuropsychiatric Symptoms in Alzheimer's Disease: A Re-Analysis of the CATIE-AD Study. J Clin Psychiatry. 2020 Feb 11;81(2):19m12961. doi: 10.4088/JCP.19m12961.
citation: Ozawa C, Roberts R, Yoshida K, Suzuki T, Lebowitz B, Reeves S, Howard R, Abe T, Mimura M, Uchida H. Placebo Effects in the Treatment of Noncognitive Symptoms of Alzheimer's Disease: Analysis of the CATIE-AD Data. J Clin Psychiatry. 2017 Nov/Dec;78(9):e1204-e1210. doi: 10.4088/JCP.17m11461.
citation: Yoshida K, Roberts R, Suzuki T, Lebowitz B, Reeves S, Howard R, Abe T, Mimura M, Uchida H. Lack of Early Improvement with Antipsychotics is a Marker for Subsequent Nonresponse in Behavioral and Psychological Symptoms of Dementia: Analysis of CATIE-AD Data. Am J Geriatr Psychiatry. 2017 Jul;25(7):708-716. doi: 10.1016/j.jagp.2017.01.016. Epub 2017 Jan 30.
citation: Miller EA, Schneider LS, Rosenheck RA. Predictors of nursing home admission among Alzheimer's disease patients with psychosis and/or agitation. Int Psychogeriatr. 2011 Feb;23(1):44-53. doi: 10.1017/S1041610210000244. Epub 2010 Mar 10.
citation: Zheng L, Mack WJ, Dagerman KS, Hsiao JK, Lebowitz BD, Lyketsos CG, Stroup TS, Sultzer DL, Tariot PN, Vigen C, Schneider LS. Metabolic changes associated with second-generation antipsychotic use in Alzheimer's disease patients: the CATIE-AD study. Am J Psychiatry. 2009 May;166(5):583-90. doi: 10.1176/appi.ajp.2008.08081218. Epub 2009 Apr 15.
citation: Sultzer DL, Davis SM, Tariot PN, Dagerman KS, Lebowitz BD, Lyketsos CG, Rosenheck RA, Hsiao JK, Lieberman JA, Schneider LS; CATIE-AD Study Group. Clinical symptom responses to atypical antipsychotic medications in Alzheimer's disease: phase 1 outcomes from the CATIE-AD effectiveness trial. Am J Psychiatry. 2008 Jul;165(7):844-54. doi: 10.1176/appi.ajp.2008.07111779. Epub 2008 Jun 2.
citation: Rosenheck RA, Leslie DL, Sindelar JL, Miller EA, Tariot PN, Dagerman KS, Davis SM, Lebowitz BD, Rabins P, Hsiao JK, Lieberman JA, Schneider LS; Clinical Antipsychotic Trial of Intervention Effectiveness-Alzheimer's Disease (CATIE-AD) investigators. Cost-benefit analysis of second-generation antipsychotics and placebo in a randomized trial of the treatment of psychosis and aggression in Alzheimer disease. Arch Gen Psychiatry. 2007 Nov;64(11):1259-68. doi: 10.1001/archpsyc.64.11.1259.