Clinical Trial: Telmisartan-Induced Reduction in Intra-Myocellular Lipids Trial

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

Official Title: A Randomized, Double Blind, 2X2 Factorial Design Study to Evaluate the Effects of Telmisartan vs Placebo, and of a Low-Glycemic Diet vs Control Diet, in Reducing Intra-Myocellular Lipids In Individual

Brief Summary: The purpose of this study is to determine whether telmisartan and/or a low-glycemic index diet are effective in reducing intra-myocellular lipid (muscle fat) content.

Detailed Summary: The metabolic syndrome currently affects over 20% of the adult population in Canada. Patients with abdominal obesity are at markedly increased risk for diabetes and heart disease. Recent studies have shown that decreased sensitivity to insulin (insulin resistance), a hallmark of the metabolic syndrome, is related to increased storage of fat in muscle cells (muscle fat). Several recent studies indicate that blocking the renin-angiotensin system (RAS) may improve insulin sensitivity and prevent the development of type 2 diabetes. Other data suggests that this effect may be due to the effect of RAS blockade on the recruitment and growth of adipose tissue. The primary aim of this study is therefore to explore the role of angiotensin II in the development of insulin resistance. Specifically, we will examine the mechanisms underlying the putative anti-diabetic effect of RAS blockade by examining the effect of angiotensin receptor blockade on muscle fat content in individuals with the abdominal obesity. This study will therefore test the hypothesis that treatment with the angiotensin receptor blocker telmisartan (Micardis®) will reduce muscle fat, thereby improving insulin sensitivity in people with abdominal obesity, with or without additional features of the metabolic syndrome. A number of dietary factors can also affect insulin sensitivity and may influence muscle fat. Recent studies suggest that increasing the content of low-glycemic foods (carbohydrates which are less easily digested), can improve insulin sensitivity and lipid profile in patients with insulin resistance. A second aim of this study is therefore to test the hypothesis that a low-glycemic diet will reduce muscle fat, thereby improving insulin sensitivity in this population.
Sponsor: McMaster University

Current Primary Outcome: (for both interventions): change in IMCL content in the soleus muscle as assessed by 1H-MRI Spectroscopy at baseline and 6 months

Original Primary Outcome: Same as current

Current Secondary Outcome:

  • Change in intra-hepatocellular lipid storage as assessed by 1H-MRI Spectroscopy
  • Change in insulin sensitivity as determined by HOMA index
  • Reversal of IFG to normal fasting glucose in participants with IFG
  • Change in 72-hour subcutaneous glucose profile
  • Change in fasting lipid profile (free fatty acids, triglyceride, total cholesterol, low-density lipoprotein (LDL) and high-density lipoprotein (HDL) cholesterol)
  • Change in serum/plasma levels of inflammatory markers (C-reactive protein, adiponectin, tumor necrosis factor a, interleukin 6, leptin, adhesion molecules, plasminogen-activation inhibitor-1, t-PA, global test of fibrinolysis, fibrinogen, homocysteine,
  • Change in beta-cell function as assessed by the Insulin Secretion Index
  • Other efficacy parameters of the AT1 blockade and LGI diet are:
  • Change in waist circumference
  • Change in body composition as assessed by bioelectrical impedance analysis
  • Change in abdominal (visceral) adipose tissue as assessed by MRI
  • Change in resting blood pressure
  • Change in adipocytic cell size determined by grouped diameter distribution in subcutaneous abdominal adipose tissue biopsies
  • Changes in mRNA expression of genes in adipose tissue for genes involved in adipose tissue differentiation, growth, metabolism, cardiovascular function and inflammation.
  • Change in muscle triglyceride content (histochemical examination of muscle biopsies)
  • Change in molecular markers of endoplasmic reticular stress in circulating blood cells
  • Endothelial function as assessed by Doppler ultrasound of the forearm blood flow.
  • Systolic and diastolic cardiac function as assessed by echocardiography


Original Secondary Outcome:

  • · Change in intra-hepatocellular lipid storage as assessed by 1H-MRI Spectroscopy
  • · Change in insulin sensitivity as determined by HOMA index
  • · Reversal of IFG to normal fasting glucose in participants with IFG
  • · Change in 72-hour subcutaneous glucose profile
  • · Change in fasting lipid profile (free fatty acids, triglyceride, total cholesterol, low-density lipoprotein (LDL) and high-density lipoprotein (HDL) cholesterol)
  • · Change in serum/plasma levels of inflammatory markers (C-reactive protein, adiponectin, tumor necrosis factor a, interleukin 6, leptin, adhesion molecules, plasminogen-activation inhibitor-1, t-PA, global test of fibrinolysis, fibrinogen, homocysteine,
  • · Change in beta-cell function as assessed by the Insulin Secretion Index
  • Other efficacy parameters of the AT1 blockade and LGI diet are:
  • · Change in waist circumference
  • · Change in body composition as assessed by bioelectrical impedance analysis
  • · Change in abdominal (visceral) adipose tissue as assessed by MRI
  • · Change in resting blood pressure
  • · Change in adipocytic cell size determined by grouped diameter distribution in subcutaneous abdominal adipose tissue biopsies
  • · Changes in mRNA expression of genes in adipose tissue for genes involved in adipose tissue differentiation, growth, metabolism, cardiovascular function and inflammation.
  • · Change in muscle triglyceride content (histochemical examination of muscle biopsies)
  • · Change in molecular markers of endoplasmic reticular stress in circulating blood cells
  • · Endothelial function as assessed by Doppler ultrasound of the forearm blood flow.
  • · Systolic and diastolic cardiac function as assessed by echocardiography


Information By: McMaster University

Dates:
Date Received: September 2, 2005
Date Started: April 2004
Date Completion:
Last Updated: December 13, 2016
Last Verified: December 2016