Alzheimer's Disease, Dementia
Conditions
Keywords
Dementia, Glutamate, Clinical Trial, Neurotransmitter, Alzheimer's Disease
Brief summary
Glutamate is an amino acid released by brain cells that acts to excite other cells. Glutamate attaches to special sites on cells called AMPA (alpha-amino-2,3-dihydro-5 methyl 3-oxo-4-isoxazolepropanoic acid) receptors. The brain cells responsible for releasing glutamate are damaged in Alzheimer's disease and other conditions affecting thinking and reasoning. Researchers would like to see if giving patients a drug that attaches to AMPA receptors improves the symptoms of Alzheimer's disease. CX516 (Ampalex) is a test drug that affects the AMPA receptors. This study will investigate the effectiveness and safety of CX516 on patients with Alzheimer's disease. Patients will be given capsules of CX516 or placebo (sugar pill that neither harms nor helps) for up to 16 weeks in different amounts. The effectiveness of the drug will be measured by neurological tests. Safety will be monitored by frequent check-ups and lab examinations.
Detailed description
Stimulation of neuronal excitatory amino acid receptors is an important step in the formation of memory. It is unknown whether stimulation of these receptors in patients with Alzheimer's disease and dementing disorders will improve cognitive function. To determine whether positive modulation of AMPA receptors, active in animal models of dementia, can improve cognitive function in demented patients, CX516, at a dose of 900mg TID, will be administered orally for 12 weeks in patients with dementia. In this randomized, controlled proof-of-principle study, drug-induced alterations in intellectual function will be measured by standardized neuropsychological tests. Safety will be monitored by frequent clinical assessments and laboratory tests.
Interventions
DRUGCX516 (Ampalex)
Sponsors
National Institute of Neurological Disorders and Stroke (NINDS)
Study design
Primary purpose
TREATMENT
Eligibility
Sex/Gender
ALL
Healthy volunteers
No
Inclusion criteria
- ALZHEIMER'S DISEASE: Study subjects will satisfy NINCDS-ADRDA criteria for probable Alzheimer's disease. Dementia severity will be mild to moderate range with Mini-Mental Status Examination total score between 12 and 26, inclusive. The modified Hachinski Ischemia Score must be less than 4, and brain MRI performed within 15 months of enrollment must be compatible with the diagnosis of Alzheimer's disease. Dementia must be present historically for at least one year. Baseline electroencephalogram must not show significant epileptiform features. INCLUSION CRITERIA - RELATED DEMENTING DISORDERS: Study subjects will show deficits in at least two cognitive spheres, including memory. Modified Hachinski Ischemia Score must be less than 4, and Folstein mini-mental status examination total score must be between 12 and 26. Cognitive difficulties must e present historically for at least one year. Brain MRI performed with 15 months of enrollment must be normal or show atrophy. Baseline electroencephalogram must not show epileptiform features. In addition, all patients must have acceptable nutritional status. Patients must be between ages 40 and 85. Patients must be sterile, post-menopausal, or using an acceptable forms of birth control. Chest x-ray within 15 months before enrollment must be acceptable for the trial. Participants in this study will reflect the diversity of those suffering from dementia. No one will be excluded or discriminated against based on the grounds of race, creed, or gender. Every attempt will be made to include women and minorities in the study population.
Exclusion criteria
- NEUROLOGIC: Hemispheric stroke, hydrocephalus, subdural hematoma, or mass lesion on neuroimaging study; epileptiform baseline EEG or known seizure disorder; head trauma with loss of consciousness concurrent with onset of dementia; chronic CNS infection (positive MHA-TP or FTA-ABS acceptable if luetic brain disease excluded by documented studies or treatment).
Countries
United States
Outcome results
None listed