Monocyte Function and Inflammation in Type 1 Diabetes and Its Modulation
Primary Purpose
Type 1 Diabetes
Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Simvastatin
Sponsored by
About this trial
This is an interventional treatment trial for Type 1 Diabetes focused on measuring diabetes, statin, monocyte, crp, inflammation
Eligibility Criteria
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
Sites / Locations
- UCDavis Medical Center
Outcomes
Primary Outcome Measures
HsCRP
Monocyte function
Secondary Outcome Measures
Plasma biomarkers
Full Information
NCT ID
NCT00441844
First Posted
February 27, 2007
Last Updated
February 28, 2007
Sponsor
University of California, Davis
Collaborators
Juvenile Diabetes Research Foundation, National Institutes of Health (NIH)
1. Study Identification
Unique Protocol Identification Number
NCT00441844
Brief Title
Monocyte Function and Inflammation in Type 1 Diabetes and Its Modulation
Official Title
Phase 2 Study Examining the Effect of Simvastatin vs Placebo on Monocyte Function and Inflammation in Patients With Type 1 Diabetes
Study Type
Interventional
2. Study Status
Record Verification Date
February 2007
Overall Recruitment Status
Completed
Study Start Date
October 2002 (undefined)
Primary Completion Date
undefined (undefined)
Study Completion Date
July 2005 (undefined)
3. Sponsor/Collaborators
Name of the Sponsor
University of California, Davis
Collaborators
Juvenile Diabetes Research Foundation, National Institutes of Health (NIH)
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
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.
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
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Type 1 Diabetes
Keywords
diabetes, statin, monocyte, crp, inflammation
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
Double
Allocation
Randomized
Enrollment
50 (false)
8. Arms, Groups, and Interventions
Intervention Type
Drug
Intervention Name(s)
Simvastatin
Primary Outcome Measure Information:
Title
HsCRP
Title
Monocyte function
Secondary Outcome Measure Information:
Title
Plasma biomarkers
10. Eligibility
Sex
All
Minimum Age & Unit of Time
20 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Ishwarlal Jialal', MD, PhD
Organizational Affiliation
UCDavis Professor
Official's Role
Principal Investigator
Facility Information:
Facility Name
UCDavis Medical Center
City
Sacramento
State/Province
California
ZIP/Postal Code
95817
Country
United States
12. IPD Sharing Statement
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Monocyte Function and Inflammation in Type 1 Diabetes and Its Modulation
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