Effects of an Anti-Inflammatory Drug in Alzheimer's Disease

NCT00013650 | Completed Phase 1

• 2 other identifiers: 01012801-M-0128
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

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 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.

Conditions

Alzheimer's Disease

Keywords

Alzheimer's Disease; Immunomodulatory; Antiinflammatory; Cyclophosphamide; Non-steroidal; Complement; Immune Function; Immunotherapy

Interventions

Cyclophosphamate DRUG

Eligibility Criteria

• Age: 50 Years - 95 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Subjects must have a diagnosis of probable Alzheimer's disease according to DSM-IV and NINDS criteria.
• Subjects must have mild-moderate severity of dementia according to the Clinical Dementia Rating Scale at the time of study.
• They must also have the ability to assign a DPA or have already assigned a DPA and give informed consent for this medication trial and be willing to undergo repeat lumbar punctures for the assessment of cerebrospinal fluid.

You may not qualify if:

• Severe dementia (CDR score greater than 2).
• Diagnosis of probable vascular dementia.
• Inability to give assent for participation or designate a durable power of attorney.
• Medication history of cytotoxic drug therapy for more than 2 weeks during the 10 weeks prior to study entry, for more than 10 weeks at any time, or for anytime during the 30 day period prior to study entry.
• Recent use of continuous (more than 3 doses per week) nonsteroidal medication (at least one month before entry). Low dose aspirin will not be considered as continuous nonsteroidal anti-inflammatory medication.
• Known hypersensitivity to CY, aspirin or any nonsteroidal medication.
• Current use of allopurinol, rifampin, methotrexate or warfarin.
• Inflammatory conditions (such as SLE, autoimmune disease, etc.) which could respond to medications given in the medication protocol.
• Medical conditions including: active or chronic infection requiring antimicrobial therapy, serious viral infection (hepatitis, herpes zoster), a single functioning kidney, renal insufficiency (less than one third of normal GFR), significant hepatic dysfunction, pre-existent malignancy, insulin-treated diabetes mellitus, severe benign prostatic hypertrophy, immunosuppression, myelosuppression, lymphopenia, severe pulmonary dysfunction, history of gastrointestinal ulceration active within the last 5 years, history of gastrointestinal bleeding or perforation, or severe cardiac dysfunction.

Sponsors & Collaborators

• National Institute of Mental Health (NIMH): lead

Study Sites (1)

National Institutes of Health Clinical Center, 9000 Rockville Pike

Bethesda, Maryland, 20892, United States

Location

Related Publications (1)

• Aisen PS, Davis KL, Berg JD, Schafer K, Campbell K, Thomas RG, Weiner MF, Farlow MR, Sano M, Grundman M, Thal LJ. A randomized controlled trial of prednisone in Alzheimer's disease. Alzheimer's Disease Cooperative Study. Neurology. 2000 Feb 8;54(3):588-93. doi: 10.1212/wnl.54.3.588.

  PMID: 10680787 BACKGROUND

MeSH Terms

Conditions

Alzheimer Disease

Condition Hierarchy (Ancestors)

Dementia; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Tauopathies; Neurodegenerative Diseases; Neurocognitive Disorders; Mental Disorders

Study Design

• Study Type: interventional
• Phase: phase 1
• Purpose: TREATMENT
• Sponsor Type: NIH

Study Record Dates

• First Submitted: March 27, 2001
• First Posted: March 28, 2001
• Study Start: March 22, 2001
• Study Completion: April 21, 2008
• Last Updated: July 2, 2017

Record last verified: 2008-04-21

Locations

US (1)