Now Available for Public Comment: Notice of Proposed Rulemaking (NPRM) for FDAAA 801 and NIH Draft Reporting Policy for NIH-Funded Trials

Monocyte Function and Inflammation in Type 1 Diabetes and Its Modulation

This study has been completed.
Sponsor:
Collaborators:
Juvenile Diabetes Research Foundation
Information provided by:
University of California, Davis
ClinicalTrials.gov Identifier:
NCT00441844
First received: February 27, 2007
Last updated: February 28, 2007
Last verified: February 2007
  Purpose

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.


Condition Intervention Phase
Type 1 Diabetes
Drug: Simvastatin
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double-Blind
Primary Purpose: Treatment
Official Title: Phase 2 Study Examining the Effect of Simvastatin vs Placebo on Monocyte Function and Inflammation in Patients With Type 1 Diabetes

Resource links provided by NLM:


Further study details as provided by University of California, Davis:

Primary Outcome Measures:
  • HsCRP
  • Monocyte function

Secondary Outcome Measures:
  • Plasma biomarkers

Estimated Enrollment: 50
Study Start Date: October 2002
Estimated Study Completion Date: July 2005
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

Ages Eligible for Study:   20 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00441844

Locations
United States, California
UCDavis Medical Center
Sacramento, California, United States, 95817
Sponsors and Collaborators
University of California, Davis
Juvenile Diabetes Research Foundation
Investigators
Principal Investigator: Ishwarlal Jialal`, MD, PhD UCDavis Professor
  More Information

No publications provided

ClinicalTrials.gov Identifier: NCT00441844     History of Changes
Other Study ID Numbers: JDFT1DMSIMVA, UCD IRB # 200210057
Study First Received: February 27, 2007
Last Updated: February 28, 2007
Health Authority: United States: Institutional Review Board

Keywords provided by University of California, Davis:
diabetes, statin, monocyte, crp, inflammation

Additional relevant MeSH terms:
Diabetes Mellitus
Diabetes Mellitus, Type 1
Inflammation
Autoimmune Diseases
Endocrine System Diseases
Glucose Metabolism Disorders
Immune System Diseases
Metabolic Diseases
Pathologic Processes
Simvastatin
Anticholesteremic Agents
Antimetabolites
Enzyme Inhibitors
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Hypolipidemic Agents
Lipid Regulating Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Therapeutic Uses

ClinicalTrials.gov processed this record on November 25, 2014