Monocyte Function and Inflammation in Type 1 Diabetes and Its Modulation

Type 1 Diabetes Clinical Trial

Official title:

Phase 2 Study Examining the Effect of Simvastatin vs Placebo on Monocyte Function and Inflammation in Patients With Type 1 Diabetes

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00441844
• Other study ID #: JDFT1DMSIMVA
• Secondary ID: UCD IRB # 200210
• Status: Completed
• Phase: Phase 2
• First received: February 27, 2007
• Last updated: February 28, 2007
• Start date: October 2002
• Est. completion date: July 2005

Study information

• Verified date: February 2007
• Source: University of California, Davis
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial 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.

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 50
• Est. completion date: July 2005
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 20 Years and older

Eligibility

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 Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double-Blind, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Diabetes Mellitus, Type 1
• Inflammation
• Type 1 Diabetes

Intervention

Drug:
• Simvastatin

Locations

Country	Name	City	State
United States	UCDavis Medical Center	Sacramento	California

Sponsors (3)

Lead Sponsor	Collaborator
University of California, Davis	Juvenile Diabetes Research Foundation, National Institutes of Health (NIH)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	HsCRP
Primary	Monocyte function
Secondary	Plasma biomarkers