Telmisartan-Induced Reduction in Intra-Myocellular Lipids Trial

December 13, 2016 updated by: McMaster University

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 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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

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.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
120

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Canada
    • Ontario
      • Hamilton, Ontario, Canada, L8L 2X2
        • Hamilton Health Sciences - Cardiovascular Obesity Research and Management Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

30 years to 70 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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 ACE-I or ARB)
  • 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 range
    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 form.
  • 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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Factorial Assignment
  • Masking: Double

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
(for both interventions): change in IMCL content in the soleus muscle as assessed by 1H-MRI Spectroscopy at baseline and 6 months

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
McMaster University

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Canadian Institutes of Health Research (CIHR)
Boehringer Ingelheim
Medtronic
Heart and Stroke Foundation of Canada

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Arya M Sharma, MD, FRCPC, McMaster University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
April 1, 2004

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
January 1, 2006

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
November 1, 2006

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
September 2, 2005

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
September 2, 2005

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
September 7, 2005

Study Record Updates

Last Update Posted (Estimate)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
December 14, 2016

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
December 13, 2016

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
December 1, 2016

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 502.433
  • BI Pharmaceuticals - 502.433
  • CIHR - 116099

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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