Clinical trial NCT00441844: 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
Overall status: COMPLETED
Phase: PHASE2
Conditions: Type 1 Diabetes
Keywords: diabetes, statin, monocyte, crp, inflammation
Lead sponsor: University of California, Davis
Sponsor class: OTHER
Collaborators: name: Juvenile Diabetes Research Foundation
name: National Institutes of Health (NIH)
First posted: 2007-03-01
Enrollment: 50
Sex: ALL
Minimum age (years): 20
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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

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

Primary outcomes:
measure: HsCRP
measure: Monocyte function
Secondary outcomes:
measure: Plasma biomarkers
Other outcomes:
Locations:
city: Sacramento
country: United States
facility: UCDavis Medical Center
state: California
Study officials:
affiliation: UCDavis Professor
name: Ishwarlal Jialal', MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: