Clinical trial NCT00000172: Evaluation of Galantamine in the Treatment of Alzheimer's Disease
Official title: Placebo Controlled Evaluation of Galantamine in the Treatment of Alzheimer's Disease: Safety and Efficacy Under a Slow-Titration Regimen
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Alzheimer Disease
Keywords: Alzheimer's disease
Cholinergic agents
Cholinergic agonists
Cholinesterase inhibitors
Lead sponsor: National Institute on Aging (NIA)
Sponsor class: NIH
First posted: 1999-11-01
Sex: ALL
Minimum age (years): 0
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Galantamine is an experimental drug being evaluated in the United States for the treatment of Alzheimer's disease. Results from previous clinical trials suggest that galantamine may improve cognitive performance in individuals with Alzheimer's disease. It is not a cure for Alzheimer's disease. Nerve cells in the brain responsible for memory and cognitive function communicate using a chemical called acetylcholine. Research has shown that deterioration of cells that produce acetylcholine in the brain affects thought processes. Galantamine is thought to work in two ways to increase the amount of acetylcholine available in the brain. It inhibits an enzyme that breaks down acetylcholine and it also stimulates the nicotinic receptors in the brain to release more acetylcholine.

Detailed description: After a 1-month single-blind run in phase, 910 subjects will be titrated, over a period of up to 8 weeks, to target doses of either: 0 (placebo); 24 mg/day galantamine; 16 mg/day galantamine; or 8 mg/day galantamine, in a 2:2:2:1 randomization ratio. Double-blind treatment will continue for a total of 5 months. The change from baseline in ADAS-cog and CIVIC-plus scores at Month 5 will be the primary efficacy endpoints. Tolerability will be evaluated based on adverse event reports, laboratory values, ECG, and vital signs with particular focus on the adverse event rates in the slower titration schedule for 24 mg/day. Efficacy of 24 mg/day and 16 mg/day galantamine will be compared with that of placebo. Information on the dose response relationship of galantamine will be evaluated.

Eligibility criteria: Inclusion Criteria:

* Probable Alzheimer's disease
* Mini-Mental State Examination (MMSE) 10-22 and ADAS greater than or equal to 18
* Alzheimer's Disease Assessment Scale cognitive portion (ADAS-cog-11) score of at least 18
* Opportunity for Activities of Daily Living
* Caregiver
* Subjects who live with or have regular daily visits from a responsible caregiver (visit frequency: preferably daily but at least 5 days/week). This includes a friend or relative or paid personnel. The caregiver should be capable of assisting with the subject's medication, prepared to attend with the subject for assessments, and willing to provide information about the subject.

Exclusion Criteria:

* Conditions that could confound diagnosis
* Neurodegenerative disorders
* Acute cerebral trauma
* Psychiatric disease
* More than one infarct on CT/MRI scans
* History of alcohol or drug abuse
* Contradictions for a cholinominetic agent: seizures; ulcers; pulmonary conditions (including severe asthma); unstable angina; Afib; bradycardia less than 50; and AV block.

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama, Birmingham
state: Alabama
city: Scottsdale
country: United States
facility: James L. Frey, M.D., Ltd.
state: Arizona
city: Berkeley
country: United States
facility: East Bay Neurology
state: California
city: Los Angeles
country: United States
facility: University of Southern California
state: California
city: Oceanside
country: United States
facility: N. County Neurology Assoc.
state: California
city: Orange
country: United States
facility: University of California Irvine Medical Center
state: California
city: San Diego
country: United States
facility: Pacific Research Network (PRN)
state: California
city: San Diego
country: United States
facility: Affiliated Research Institute
state: California
city: San Diego
country: United States
facility: INC
state: California
city: Denver
country: United States
facility: The Denver Center for Medical Research
state: Colorado
city: Hamden
country: United States
facility: Geriatric and Adult Psychiatry
state: Connecticut
city: New Haven
country: United States
facility: Yale University, School of Medicine
state: Connecticut
city: Ocala
country: United States
facility: Ocala Neurodiagnostic Center
state: Florida
city: Orlando
country: United States
facility: Psychiatric Institute of Florida
state: Florida
city: Sarasota
country: United States
facility: Neurological Research Institute of Sarasota, PA
state: Florida
city: St. Petersburg
country: United States
facility: Suncoast Neuroscience Associates, Inc.
state: Florida
city: West Palm Beach
country: United States
facility: Premiere Research Institute
state: Florida
city: Chicago
country: United States
facility: Chicago Center for Clinical Research
state: Illinois
city: Peoria
country: United States
facility: OSF Center for Senior Health
state: Illinois
city: Indianapolis
country: United States
facility: Indiana Alzheimer's University Clinic
state: Indiana
city: Baltimore
country: United States
facility: The Johns Hopkins Hospital
state: Maryland
city: Boston
country: United States
facility: Brigham Behavioral Neurology Group
state: Massachusetts
city: Wellesley Hills
country: United States
facility: Boston Clinical Research Center
state: Massachusetts
city: Worcester
country: United States
facility: University of Massachusetts Worcester
state: Massachusetts
city: Dearborn
country: United States
facility: Oakwood Hospital and Medical Center
state: Michigan
city: Grand Rapids
country: United States
facility: Michigan Medical P.C.
state: Michigan
city: St. Paul
country: United States
facility: Regions Hospital
state: Minnesota
city: St. Louis
country: United States
facility: St. Louis University School of Medicine
state: Missouri
city: St. Louis
country: United States
facility: Washington University
state: Missouri
city: Omaha
country: United States
facility: University of Nebraska
state: Nebraska
city: Piscataway
country: United States
facility: University of Medicine and Dentistry of New Jersey
state: New Jersey
city: Ridgewood
country: United States
facility: Neurology Group of Bergen County
state: New Jersey
city: Summit
country: United States
facility: Overlook Hospital
state: New Jersey
city: West Long Branch
country: United States
facility: Medwise Center
state: New Jersey
city: Albany
country: United States
facility: Neurological Associates of Albany, PC
state: New York
city: Centereach
country: United States
facility: East End Neuropsychiatric Associates
state: New York
city: Far Rockaway
country: United States
facility: St. John's Episcopal Hospital
state: New York
city: New York
country: United States
facility: NYU Medical Center
state: New York
city: Rochester
country: United States
facility: University of Rochester
state: New York
city: Stony Brook
country: United States
facility: SUNY Stony Brook
state: New York
city: Columbus
country: United States
facility: Ohio State University
state: Ohio
city: Tulsa
country: United States
facility: Clinical Pharmaceutical Trials
state: Oklahoma
city: Portland
country: United States
facility: Oregon Health Sciences University
state: Oregon
city: Portland
country: United States
facility: Pacific NW Clinical Research Center
state: Oregon
city: Elkins Park
country: United States
facility: Institute for Advanced Clinical Research
state: Pennsylvania
city: Greensburg
country: United States
facility: Neuroscience Center of Westmoreland Neurology
state: Pennsylvania
city: Pawtucket
country: United States
facility: Brown University
state: Rhode Island
city: North Charleston
country: United States
facility: Alzheimer's Research and Clinical Programs
state: South Carolina
city: Dallas
country: United States
facility: University of Texas
state: Texas
city: Bennington
country: United States
facility: Southwestern Vermont Medical Center
state: Vermont
city: Colchester
country: United States
facility: Memory Disorder Center of Vermont
state: Vermont
city: Alexandria
country: United States
facility: Virginia Neuroscience Center
state: Virginia
city: Manassas
country: United States
facility: Prince William Neuroscience Center
state: Virginia
city: Seattle
country: United States
facility: Seattle Clinical Research Center
state: Washington
city: Seattle
country: United States
facility: VAPS Health Care System
state: Washington
Study officials:
References:
citation: Lilienfeld S, Parys W. Galantamine: additional benefits to patients with Alzheimer's disease. Dement Geriatr Cogn Disord. 2000 Sep;11 Suppl 1:19-27. doi: 10.1159/000051228.