UNC expands national clinical trials of schizophrenia and Alzheimer's drugs

CHAPEL HILL - The University of North Carolina's Department of Psychiatry is expanding its large-scale effectiveness trials of anti-psychotic medications for schizophrenia and behavioral problems in Alzheimer's disease to include a newly-approved drug. The National Institute of Mental Health (NIMH) is providing an additional $18 million to the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) project, bringing the total contract to $60 million.

The two CATIE trials are examining which of the new generation of anti-psychotic drugs are best for patients with schizophrenia and disruptive behaviors associated with Alzheimer's disease. Completion of the trials is set for September 2004, but terms of the NIMH contract include an option for a five-year extension and expansion studies.

The study was originally designed to examine the effectiveness of the various classes of anti-psychotic drugs represented by clozapine, risperidone, olanzapine, quetiapine and perphenazine. Now ziprasidone, which received Food and Drug Administration (FDA) approval last February, will be added to the schizophrenia trial.

Once the FDA deemed ziprasidone effective in treating psychosis in schizophrenia, CATIE investigators proposed adding it to enhance the scientific value and clinical relevance of the study's results.

"The major objective of the CATIE trials is to determine the most effective treatments in real-world settings, so it's important that we examine new medications as they become available to patients," explained Dr. Jeffrey A. Lieberman, CATIE's principal investigator. Lieberman is a professor of psychiatry, pharmacology and radiology at the UNC-Chapel Hill School of Medicine.

"Unlike smaller studies of the past, the CATIE trials embrace a broader public health model of intervention," said NIMH Acting Director Richard K. Nakamura, Ph.D. "We hope to gain important information on cost effectiveness and patient adherence to the treatment." Unlike first generation anti-psychotic agents, which act primarily on the brain's dopamine system, the newer drugs being studied by the CATIE project also act on serotonin and nonrepinephrine systems. They also cost at least 10 times more than the first generation anti-psychotics. CATIE results will help determine if they are effective and whether they are worth the higher price.

"The relative effectiveness of ziprasidone and other drugs in the study is undetermined," Dr. Lieberman said. "CATIE research will provide a definitive comparison so that health-care providers can make informed choices about treatment."

CATIE is a multi-institutional effort led by UNC-Chapel Hill and managed by Quintiles Inc. of Research Triangle Park, N.C. UNC-Chapel Hill is working with other academic centers to coordinate the trials, involving faculty from Duke University, the University of Southern California, Yale University and the University of Rochester.

Dr. Lieberman and Dr. C.E. Davis, professor and chair of biostatistics at the UNC-Chapel Hill School of Public Health, are the project's co-principal investigators. Lon Schneider, M.D., professor of psychiatry, neurology, and gerontology at USC, and Pierre Tariot, M.D., professor of psychiatry and neurology at the University of Rochester direct the Alzheimer's disease trials.

Key investigators from UNC-Chapel Hill are Scott Stroup, M.D., M.P.H., and Diana Perkins, M.D., M.P.H. Other researchers involved in trial management are Joseph McEvoy, M.D., Marvin Swartz, M.D., and Richard Keefe, Ph.D. at Duke and Robert Rosenheck, M.D. at Yale. UNC-Chapel Hill was tapped for the project in 1999 and began enrolling participants in December 2000. Currently, 90 clinical sites in 38 states have enrolled more than 700 patients. Sites in North Carolina include UNC-Chapel Hill; Duke; John Umstead Hospital in Butner; Dorothea Dix Hospital in Raleigh; Wake Forest University School of Medicine in Winston-Salem; and the Behavioral Health Center in Charlotte.

CATIE TRIAL LOCATIONS Schizophrenia and Alzheimer's disease studies are being conducted at the following locations:

Alabama
Tuscaloosa VA Medical Center

California
University of Southern California/Dept of Psychiatry & Behavioral Sciences, Los Angeles
Synergy Clinical Research, Chula Vista
University of California, Los Angeles, VA Medical Center
Stanford University School of Medicine
Harbor UCLA Research & Education Institute, Torrance
University of California, Irvine
University of California-San Diego, VA Medical Center
VA-San Diego Healthcare System, La Jolla
LA County-University of Southern California Medical Center, Los Angeles

Connecticut
Yale University/Connecticut Mental Health Center, New Haven
New Britain General Hospital, New Britain

Florida
Henderson Mental Health Center, Ft. Lauderdale
University of Miami School of Medicine
VA Medical Center, Miami
University of South Florida Suncoast Gerontology Center, Tampa
Palm Beach Neurology/Premier Research Institute, West Palm Beach
Mental Health Associates, Inc., Boca Raton

Georgia
Emory University School of Medicine, Atlanta
Wesley Woods Health Center, Atlanta

Hawaii
The Queen's Medical Center, Honolulu
University of Hawaii, Honolulu

Illinois
Northwestern Medical School Department of Psychiatry/Northwestern Medical School, Chicago Northwestern University Medical School
SIU School of Medicine, Springfield
Southern Illinois School of Medicine, Springfield

Iowa
University of Iowa College of Medicine, Iowa City

Kansas
Psychiatric Research Institute, Outpatient Clinic, Wichita

Louisiana
Louisiana State University Health Services Center, Shreveport

Maryland
Clinical Insights, Inc., Glen Burnie
Johns Hopkins University, Baltimore

Massachusetts
Massachusetts General Hospital-Freedom Trial Clinic Schizophrenia Program, Boston
St. Elizabeth's Medical Center, Boston
University Of Massachusetts Health Care, Worcester
Corrigan Mental Health Center, Fall River

Mississippi
University of Mississippi, Jackson

Missouri Burrell Behavioral Health-Cox North Hospital, Springfield
University of Missouri Kansas City Medical School
Washington University School of Medicine, St. Louis
St. Louis University School of Medicine-Wohl Institute

New Hampshire
Dartmouth Hitchcock Medical Center, Lebanon
Dartmouth Hitchcock Medical Center, Manchester
Frisbie Memorial Hospital, Rochester

New Mexico
Albuquerque VA Medical Center

New York Columbia University, New York
Staten Island University Hospital
Mount Sinai Medical Center-Bronx VA Medical Center
Mount Sinai Medical Center, New York
Monroe Community Hospital, Rochester
Nathan S. Kline Institute, Orangeburg
University of Rochester Medical Center

North Carolina
University of North Carolina School of Medicine, Chapel Hill
Dorothea Dix Hospital, Raleigh
Duke University Medical Center, Durham
Duke University Medical Center-John Umstead Hospital, Butner
Wake Forest University School of Medicine, Winston Salem
Behavioral Health Center, Charlotte

Ohio
Appalachian Psychiatric Healthcare System, Athens
University Hospitals Health Systems, Willoughby

Pennsylvania
Eastern Pennsylvania Psychiatric Institute, Philadelphia
Behavioral Health Service, Philadelphia
University of Pittsburgh AD Research Center
Mental Illness Research Education and Clinical Center, Philadelphia
VA Medical Center, Coatesville

South Carolina
Medical University of South Carolina, Charleston
Veterans Affairs Medical Center, Charleston

Tennessee
Vanderbilt University Medical Center, Nashville

Texas
Tri-County MHMR Services, Conroe
University of Texas Southwestern Medical Center, Dallas
MHMRA of Harris County-Northwest Community Service Center, Houston
Life Management Center for MH/MR Services, El Paso
The Center for Health Care Services, San Antonio
University of Texas Health Sciences, San Antonio

Utah Valley Mental Health Psychopharmacology Research Center, Salt Lake City

Washington
VA Puget Sound Health Care System, Tacoma