Ignite Creation Date:
2024-05-05 @ 11:23 AM
Last Modification Date:
2024-10-26 @ 9:06 AM
Study NCT ID:
NCT00013650
Status:
COMPLETED
Last Update Posted:
2017-07-02
First Post:
2001-03-27
Brief Title:
Effects of an Anti-Inflammatory Drug in Alzheimers Disease
Sponsor:
National Institute of Mental Health NIMH
Organization:
National Institutes of Health Clinical Center CC
Study Overview
Official Title:
Pilot Study of Immunomodulatory Versus Antiinflammatory Therapy in Alzheimers Disease
Status:
COMPLETED
Status Verified Date:
2008-04-21
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
The purpose of this study is to evaluate the effects of the drug cyclophosphamide CY on inflammation and immune responses in individuals with Alzheimers 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
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
Detailed Description:
Objectives The protocol is focused on the immune and inflammatory reactions in Alzheimers disease AD and the possibility that blocking the inflammatory response may alter the course of the illness The specific plan is to evaluate the biologic and clinical effects of two doses of cyclophosphamide CY immunotherapy in AD patients compared to the clinically available cyclooxygenase-2 inhibitor COX-2 rofecoxib The study will test the hypotheses that CY 1 Is safe and tolerable in AD patients in meaningful clinical doses 2 Can modify central nervous system inflammation and immune responses in AD 3 Inhibits neurodegeneration in AD brains as indicated by peripheral biomarkers of AD pathology and 4 Is different quantitatively or qualitatively in its effect on immune markers than placebo or other clinically-available anti-inflammatory drugs such as the COX-2 inhibitor rofecoxib
Rationale Inflammation and immunologic responses appear to contribute significantly to neurodegeneration in AD In a pathological process termed gliosis the brains resident immune cells microglia and astroglia undergo chronic activation and possible proliferation promoting neuronal injury and death by several means Activated microglia and astroglia produce compounds that are directly 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 hastening the demise of synapses and neurons in AD Conversely the growing understanding of immune and inflammatory pathology in AD has provided new opportunities for designing disease-altering treatments for AD Preliminary clinical trials of anti-inflammatory drugs in AD patients epidemiologic studies of anti-inflammatory drug use and experimental models linking neurodegeneration with neuroimmuneneuroinflammatory processes suggest strongly 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 acts primarily by inhibiting proliferation of immune cells Moreover as immune cell proliferation appears to be an important aspect of AD pathophysiology and disease progression an exploratory dose-finding trial of a cytotoxiccytostatic drug such as CY is appropriate especially since CY is already widely used for the treatment of other immune-mediated illnesses Furthermore a preliminary European trial of CY in AD patients has already demonstrated an improvement in cognitive function that correlated highly with the degree of immunomodulation achieved
Design Study subjects will include 60 male and female patients with mild-moderate AD In a randomized placebo-controlled trial two doses of CY or rofecoxib will be compared over a 6-month period While the primary outcome measures will be safety and immunologic data cognitive and other behavioral measures will also be collected The biological outcome measures will include measures of brain volume assessed by magnetic resonance imaging and cerebrospinal fluid biomarkers of neurodegeneration neuroinflammation and neuroimmune activation In addition peripheral lymphocyte subsets and peripheral markers of inflammation will be assessed This design is meant to provide dose-finding data to help design a more definitive efficacy trial with CY if the safetytolerability parameters are acceptable in this pilot study
Rationale Inflammation and immunologic responses appear to contribute significantly to neurodegeneration in AD In a pathological process termed gliosis the brains resident immune cells microglia and astroglia undergo chronic activation and possible proliferation promoting neuronal injury and death by several means Activated microglia and astroglia produce compounds that are directly 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 hastening the demise of synapses and neurons in AD Conversely the growing understanding of immune and inflammatory pathology in AD has provided new opportunities for designing disease-altering treatments for AD Preliminary clinical trials of anti-inflammatory drugs in AD patients epidemiologic studies of anti-inflammatory drug use and experimental models linking neurodegeneration with neuroimmuneneuroinflammatory processes suggest strongly 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 acts primarily by inhibiting proliferation of immune cells Moreover as immune cell proliferation appears to be an important aspect of AD pathophysiology and disease progression an exploratory dose-finding trial of a cytotoxiccytostatic drug such as CY is appropriate especially since CY is already widely used for the treatment of other immune-mediated illnesses Furthermore a preliminary European trial of CY in AD patients has already demonstrated an improvement in cognitive function that correlated highly with the degree of immunomodulation achieved
Design Study subjects will include 60 male and female patients with mild-moderate AD In a randomized placebo-controlled trial two doses of CY or rofecoxib will be compared over a 6-month period While the primary outcome measures will be safety and immunologic data cognitive and other behavioral measures will also be collected The biological outcome measures will include measures of brain volume assessed by magnetic resonance imaging and cerebrospinal fluid biomarkers of neurodegeneration neuroinflammation and neuroimmune activation In addition peripheral lymphocyte subsets and peripheral markers of inflammation will be assessed This design is meant to provide dose-finding data to help design a more definitive efficacy trial with CY if the safetytolerability parameters are acceptable in this pilot study
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| 01-M-0128 | None | None | None |