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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 Individuals With Abdominal Obesity

Phase 3
30 Years
70 Years
Open (Enrolling)
Metabolic Syndrome X

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Trial Information

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 Individuals With Abdominal Obesity

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.

Inclusion Criteria:

- Written informed consent

- Between 30 and 70 years of age

- Abdominal obesity defined as increased waist circumference (Men >102cm (>40in), Women
>88cm (>35in)), with or without any of the following additional criteria of the
metabolic syndrome:

- Triglycerides >=1.7mmol/L (>=150 mg/dL and/or on prescribed lipid lowering medication
for > 3 months)

- HDL cholesterol

- Men <1.0 mmol/L (<40 mg/dL)

- Women <1.3 mmol/L (<50 mg/dL)

- Blood pressure >=130 and/or >=85 mmHg and/or on anti-hypertensive therapy (except

- Fasting glucose >=6.1 mmol/L (>=110 mg/dL)

- Ability and willingness to complete dietary and activity diaries and questionnaires.

Exclusion Criteria:

- Participant has taken ACE inhibitor or ARB in the last 3 months, or in the opinion of
the study physician currently has indication for either of these medications

- Concurrent antidiabetic medication

- Use of systemic glucocorticosteroids (topical and inhaled are acceptable)

- On lipid-lowering medication and NOT on stable dose for the last three months

- If the participant has any one or more of the following medical disorders:

1. diabetes mellitus and/or FBG >=7.0 mmol/L on two separate occasions within the
screening period

2. uncontrolled hypertension (SBP >=160 mmHg and/or DBP >=100 mmHg) or known
participants with secondary causes of hypertension

3. biliary obstruction

4. hepatic dysfunction as defined by SGPT (ALT) > 3 times the upper limit of normal

5. renal dysfunction as defined by serum creatinine > 130umol/L AND/OR proteinuria
1+ or greater (dipstick)

6. serum triglycerides >10 mmol/L

7. history of hypertrophic obstructive cardiomyopathy, hemodynamically relevant
stenosis of the aortic or mitral valve

8. sodium depletion or hyperkalemia.

9. uncorrected volume depletion

10. endocrine disorder (e.g. hyperthyroidism, Cushing’s syndrome, acromegaly, etc.)
Participants on thyroid-replacement therapy and TSH < 5.0 mU/L may be enrolled
in the study.

11. contraindications to study diet

12. any major surgery that is, at the time of screening, planned to take place
during the study period.

13. previously angioedema with ACE Inhibitor or ARB or known hypersensitivity to any
component of the study drug formulations (e.g. hereditary fructose intolerance)

14. history of drug or alcohol dependency within six months prior to signing the
informed consent form.

15. history of active malignancy, chronic inflammatory disorder, or chronic
infections which would interfere with protocol completion.

16. any other medical, social or geographic condition, which, in the opinion of the
investigator would not allow safe completion of the protocol and/or safe
administration of trial medication

- If the participant has any contraindications to MRI

- Pre-menopausal women (last menstruation >=1 year prior to consent) who:

1. are not surgically sterile or

2. are nursing, or pregnant, or

3. are of child-bearing potential and are NOT practicing acceptable methods of
birth control, or do NOT plan to continue practicing an acceptable method
throughout the study, AND do not agree to periodic pregnancy testing during
participation in the study.

- Intention to go on weight - reducing medications or weight-loss diets during the
study period

- Significant fluctuations in weight over past 3 months(e.g. >10%)

- Household member currently in study

- Any investigational drug therapy within one month of signing the informed consent

- Participant has knowledge that he/she will be unable to consume study foods for >2
weeks during treatment phase of study

- <70% compliant during run-in

- Unable to reduce total fat consumption to <40% and/or reduce saturated fat
consumption to <15% during run-in

Type of Study:


Study Design:

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

Outcome Measure:

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

Principal Investigator

Arya M Sharma, MD, FRCPC

Investigator Role:

Principal Investigator

Investigator Affiliation:

McMaster University


Canada: Health Canada

Study ID:




Start Date:

April 2004

Completion Date:

November 2006

Related Keywords:

  • Metabolic Syndrome X
  • insulin resistance, myocellular lipids, adipose tissue
  • Obesity, Abdominal
  • Metabolic Syndrome X