- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00441844
Monocyte Function and Inflammation in Type 1 Diabetes and Its Modulation
Phase 2 Study Examining the Effect of Simvastatin vs Placebo on Monocyte Function and Inflammation in Patients With Type 1 Diabetes
Type I diabetes (T1DM) is associated with an increased risk of vascular complications. While the precise mechanism(s) by which diabetes accelerates atherosclerosis has not been elucidated, several lines of evidence point to the role of increased inflammation in the pathogenesis of these vasculopathies. The monocyte-macrophage is a pivotal cell in atherogenesis and is readily accessible for study. However, there is scanty data on monocyte function and inflammation in T1DM. Simvastatin, a HMG-CoA reductase inhibitor, has recently been shown to reduce cardiovascular events in diabetic patients (T1DM and T2DM in the Heart Protection Study). Recent studies demonstrate that simvastatin decreased C-reactive protein and decreased pro-atherogenic activity of monocytes in non-diabetic subjects. However, there is a paucity of data on the effect of simvastatin on inflammation and monocyte function in Type 1 diabetes.
Thus, the purpose of this study is Aim 1) to assess biomarkers of inflammation in T1DM compared to matched controls (n=50/group). Aim 2) Also, we will assess the effect of simvastatin (20mg/day) therapy on inflammation and monocyte function in T1DM in a randomized, placebo-controlled, double blind trial.
Study Overview
Detailed Description
Type I diabetes (T1DM) is associated with an increased risk of vascular complications. While the precise mechanism(s) by which diabetes accelerates atherosclerosis has not been elucidated, several lines of evidence point to the role of increased inflammation in the pathogenesis of these vasculopathies. The monocyte-macrophage is a pivotal cell in atherogenesis and is readily accessible for study. However, there is scanty data on monocyte function and inflammation in T1DM. Simvastatin, a HMG-CoA reductase inhibitor, has recently been shown to reduce cardiovascular events in diabetic patients (T1DM and T2DM in the Heart Protection Study). Recent studies demonstrate that simvastatin decreased C-reactive protein and decreased pro-atherogenic activity of monocytes in non-diabetic subjects. However, there is a paucity of data on the effect of simvastatin on inflammation and monocyte function in Type 1 diabetes.
Thus, the purpose of this study is Aim 1) to assess biomarkers of inflammation in T1DM compared to matched controls (n=50/group). Aim 2) Also, we will assess the effect of simvastatin (20mg/day) therapy on inflammation and monocyte function in T1DM in a randomized, placebo-controlled, double blind trial.
At baseline and post-therapy, fasting blood will be obtained for routine laboratories (including lipid profile, glucose, glycated hemoglobin), free fatty acid levels, biomarkers of inflammation [high sensitive C-reactive protein, plasma soluble cell adhesion molecules (sVCAM,sICAM, sE-selectin and sP-selectin) , CD40 ligand, monocyte pro-atherogenic activity (superoxide anion, monocyte chemotactic protein-1, interleukin (IL)-1b, IL-6 and tumor necrosis factor-a release, adhesion to human aortic endothelium, CD40 expression)] etc., and 24-hour urine for microalbumin
Study Type
Enrollment
Phase
- Phase 2
Contacts and Locations
Study Locations
-
-
California
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Sacramento, California, United States, 95817
- UCDavis Medical Center
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Type I diabetic patients (onset < 20years and on insulin therapy since diagnosis) without clinical macrovascular complications, present age > 20 years with duration of diabetes > 1yr.
Exclusion Criteria:
- HbA1c over the last year >10%
- Patients on glucophage and/or the thiazolidenediones will be excluded, since these drugs appear to be anti-inflammatory.
- Theumatoid arthritis;
- Abnormal liver function,
- Hypo- or hyperthyroidism;
- Malabsorption;
- Steroid therapy,
- Anti-inflammatory drugs except aspirin (81mg/day)
- Pregnancy,
- Lactation,
- Smoking,
- Abnormal complete blood count; and
- Alcohol consumption > 1 oz/day
Study Plan
How is the study designed?
Design Details
- Primary Purpose: TREATMENT
- Allocation: RANDOMIZED
- Interventional Model: PARALLEL
- Masking: DOUBLE
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
---|
HsCRP
|
Monocyte function
|
Secondary Outcome Measures
Outcome Measure |
---|
Plasma biomarkers
|
Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: Ishwarlal Jialal', MD, PhD, UCDavis Professor
Study record dates
Study Major Dates
Study Start
Study Completion
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (ESTIMATE)
Study Record Updates
Last Update Posted (ESTIMATE)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Pathologic Processes
- Glucose Metabolism Disorders
- Metabolic Diseases
- Immune System Diseases
- Autoimmune Diseases
- Endocrine System Diseases
- Diabetes Mellitus
- Diabetes Mellitus, Type 1
- Inflammation
- Molecular Mechanisms of Pharmacological Action
- Enzyme Inhibitors
- Antimetabolites
- Anticholesteremic Agents
- Hypolipidemic Agents
- Lipid Regulating Agents
- Hydroxymethylglutaryl-CoA Reductase Inhibitors
- Simvastatin
Other Study ID Numbers
- JDFT1DMSIMVA
- UCD IRB # 200210057
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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