Effects of an Anti-Inflammatory Drug in Alzheimer's Disease
Status:
Completed
Trial end date:
2008-04-21
Target enrollment:
Participant gender:
Summary
The purpose of this study is to evaluate the effects of the drug cyclophosphamide (CY) on
inflammation and immune responses in individuals with Alzheimer's Disease (AD).
Inflammation and immunologic response appear to contribute to neurodegeneration in people
with AD. In a process called gliosis, the brain immune cells microglia and astroglia undergo
activation and possible proliferation, which promotes neuronal injury and death. Activated
microglia and astroglia produce compounds that are cytotoxic to neurons, and they express
molecules that greatly amplify immune and inflammatory processes in the brain. Excessive
glial activation and proliferation are thought to be pivotal events that hasten the demise of
synapses and neurons in AD. Fortunately, increased understanding of immune and inflammatory
pathology in AD has provided new opportunities for designing disease-altering treatments for
AD. Studies suggest that medications such as nonsteroidal anti-inflammatory drugs (NSAIDs)
and immunomodulatory agents may have an important role in altering the course of AD. CY is a
potent anti-inflammatory and immunomodulatory drug that inhibits proliferation of immune
cells. This study will evaluate the effects of CY on individuals with mild to moderate AD.
Participants in this study will be randomly assigned to receive either two different doses of
CY or placebo (an inactive pill) for 6 months. Participants who receive placebo during the 6
months will have the option of receiving CY for an additional 6 months. Participants will
undergo magnetic resonance imaging (MRI) scans of the brain. Measures of cerebral spinal
fluid biomarkers or neurodegeneration, neuroinflammation, and neuroimmune activation will be
taken. In addition, peripheral lymphocyte subsets and peripheral markers of inflammation will
be assessed.