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Improving Metabolic Health in Patients With Diastolic Dysfunction (MTG)

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ClinicalTrials.gov Identifier: NCT03448185
Recruitment Status : Recruiting
First Posted : February 27, 2018
Last Update Posted : February 27, 2018
Sponsor:
Information provided by (Responsible Party):
University of Texas Southwestern Medical Center

Brief Summary:
The purpose of this study is to determine whether 1 year of supervised exercise training in obese individuals at high risk for developing HF, incorporating high intensity interval training (HIIT) two to three times per week in conjunction with daily oral administration of omega-3 poly-unsaturated fatty acids will lead to reduction in visceral adiposity, regression of myocardial triglyceride levels and improvements in cardiac diastolic and vascular function.

Condition or disease Intervention/treatment Phase
Obesity Heart Failure, Diastolic Metabolic Syndrome Behavioral: High intensity exercise Dietary Supplement: Omega-3 fish oil Behavioral: Yoga Dietary Supplement: olive oil capsules Not Applicable

Detailed Description:

The global objective of this project is to test novel strategies to prevent obesity related abnormalities in diastolic function that may progress to heart failure with preserved ejection fraction (HFpEF). These include: a) identifying high risk individuals by using population derived imaging and blood biomarkers; and b) implementing novel exercise training and "nutri-ceutical" strategies in obese middle aged individuals with high amounts of visceral fat, an important risk factor in the development of heart failure and adverse cardiac remodeling.

Prior work has demonstrated that: a) high levels of myocardial triglyceride content are associated with a smaller and less distensible left ventricle with reduced tissue relaxation rates compared to those with low levels and b) low fitness and high body mass index were the strongest predictors of elevated myocardial content. The consequences of excess visceral adiposity (intra- and retro-peritoneal adipose tissue) on cardiac remodeling suggest individuals with high visceral fat content and low fitness are at particularly high risk for heart failure.

The primary objective of this project is therefore to identify high risk, sedentary, middle aged obese individuals with high visceral fat levels, and initiate an exercise program in conjunction with omega-3 fatty acid supplementation designed to reduce visceral adiposity and regress myocardial triglyceride accumulation. Findings from this aim would have enormous public health significance and establish a novel, practical exercise training program and "nutria-ceutical" strategy to reverse obesity related cardiovascular remodeling.

Hypothesis:

High aerobic exercise training in conjunction with daily omega-3 supplementation will reduce visceral myocardial triglyceride accumulation by reducing visceral adiposity. A reduction of myocardial fat will lead to improved LV structure and diastolic function by an approach that is not necessarily predicated on weight loss.

Specific Aim:

To test our hypothesis that reduction in myocardial triglyceride content will improve markers of diastolic function, we have designed a randomized, double blind, placebo controlled trial. We will study four groups of previously sedentary obese middle aged subjects at high risk for development of HF for one year with the following interventions: A) sedentary controls taking placebo; B) sedentary subjects taking omega-3 fatty acids; C) subjects undergoing high intensity aerobic exercise training while on placebo and D) subjects undergoing high intensity aerobic exercise training while taking omega-3 fatty acids. Subjects will be categorized as high risk and enrolled on the basis of elevated serum biomarkers (cTnT) and high visceral fat content (>2.5 kg). We will perform comprehensive non-invasive assessments of cardiovascular structure and systolic/diastolic function before and after 1 year of an exercise intervention involving high intensity intervals and omega-3 administration. We anticipate the combination of high intensity aerobic exercise in conjunction with high dose omega-3 supplementation will reduce visceral adiposity, decrease myocardial triglyceride content and improve markers of diastolic and vascular function.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 80 participants
Allocation: Randomized
Intervention Model: Factorial Assignment
Intervention Model Description: 2x2 factorial design. Subjects are randomized to aerobic exercise or yoga as well as high dose omega-3 fatty acids or olive oil placebo.
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Masking Description: Subjects and investigative team (except for statistician) are blinded to omega-3 vs olive oil placebo. Subjects and investigators are aware of exercise modality. Outcomes assessors are blinded to all aspects of subject randomization.
Primary Purpose: Treatment
Official Title: Reduction of Cardiac Steatosis and Improvement of Diastolic Function by Modulating Metabolic Health in Obese Individuals
Actual Study Start Date : June 1, 2015
Estimated Primary Completion Date : June 1, 2019
Estimated Study Completion Date : June 1, 2019

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Placebo Comparator: Control
Subjects randomized to control group will receive olive oil placebo capsules and yoga intervention for 1 year.
Behavioral: Yoga
Subjects randomized to yoga will undergo yoga training as a control to those randomized to high intensity aerobic exercise.

Dietary Supplement: olive oil capsules
Subjects randomized to receive olive oil placebo will take 1 gram total of olive oil capsule per day.

Experimental: Exercise and omega-3 fatty acids
Subjects will receive high dose omega-3 fatty acids as well as aerobic exercise intervention for 1 year.
Behavioral: High intensity exercise
Subjects will be randomized to the exercise groups will undergo 1 year aerobic exercise training comprised of high intensity exercise sessions 2-3 days per week. Sessions will be supervised remotely via heart rate monitors.

Dietary Supplement: Omega-3 fish oil
Subjects randomized to omega-3 fatty acids will take 2 grams total of omega-3 per day for 1 year.

Active Comparator: Yoga and omega-3 fatty acids
Subjects will receive high dose omega-3 fatty acids as well as yoga intervention for 1 year.
Dietary Supplement: Omega-3 fish oil
Subjects randomized to omega-3 fatty acids will take 2 grams total of omega-3 per day for 1 year.

Behavioral: Yoga
Subjects randomized to yoga will undergo yoga training as a control to those randomized to high intensity aerobic exercise.

Active Comparator: Exercise control
Subjects will receive olive oil placebo as well as aerobic exercise intervention for 1 year.
Behavioral: High intensity exercise
Subjects will be randomized to the exercise groups will undergo 1 year aerobic exercise training comprised of high intensity exercise sessions 2-3 days per week. Sessions will be supervised remotely via heart rate monitors.

Dietary Supplement: olive oil capsules
Subjects randomized to receive olive oil placebo will take 1 gram total of olive oil capsule per day.




Primary Outcome Measures :
  1. Myocardial lipid content [ Time Frame: 1 year ]
    Myocardial triglyceride (lipid) content will be measured using cardiac nuclear magnetic resonance spectroscopy.


Secondary Outcome Measures :
  1. Cardiorespiratory fitness [ Time Frame: 1 year ]
    Change in peak VO2

  2. Arterial stiffness [ Time Frame: 1 year ]
    Changes in markers of arterial stiffness

  3. Diastolic function [ Time Frame: 1 year ]
    Changes in diastolic function

  4. Left ventricular mass and volume [ Time Frame: 1 year ]
    Changes in left ventricular morphology and remodeling



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Ages Eligible for Study:   40 Years to 60 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  1. ejection fraction >0.50
  2. >2.0 kg visceral fat (intra- and retro-peritoneal adipose tissue)
  3. either a high sensitivity troponin (>1pg/ml), or NTBNP (>40 ng/ml)
  4. age range 40 -60
  5. BMI range 30 - 50 kg/m2

Exclusion Criteria:

  1. age < 40 or > 60
  2. body mass index > 50, < 30 kg/m2
  3. history of insulin dependent diabetes, heart failure, myocarditis, restrictive cardiomyopathy, permanent/persistent atrial fibrillation, severe chronic obstructive pulmonary disease, unstable coronary artery disease or recent (<12 month) acute coronary syndrome, cerebrovascular disease as evidenced by prior transient ischemic attack or stroke and active/recent tobacco use (quit < 5 years).
  4. Female patients will be excluded if they are pregnant or plan to become pregnant (expected rare occurrence in the selected age range of 40 - 60). 5. Patients will be excluded if they are taking non-statin lipid lowering agents (fibrates, niacin, or fish oils)
  5. Contra-indications to MRI

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03448185


Contacts
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Contact: Satyam Sarma, MD 214-345-7111 Satyam.Sarma@UTSouthwestern.edu

Locations
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United States, Texas
The Institute for Exercise and Environmental Medicine Recruiting
Dallas, Texas, United States, 75231
Contact: Mary B Childers    214-345-6459    MaryBChilders@texashealth.org   
Principal Investigator: Benjamin D Levine, M.D.         
Sponsors and Collaborators
University of Texas Southwestern Medical Center
Investigators
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Study Director: Benjamin D Levine, MD University of Texas Southwestern Medical Center

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Responsible Party: University of Texas Southwestern Medical Center
ClinicalTrials.gov Identifier: NCT03448185     History of Changes
Other Study ID Numbers: STU 062014-067
First Posted: February 27, 2018    Key Record Dates
Last Update Posted: February 27, 2018
Last Verified: February 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
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Heart Failure
Metabolic Syndrome
Heart Failure, Diastolic
Heart Diseases
Cardiovascular Diseases
Insulin Resistance
Hyperinsulinism
Glucose Metabolism Disorders
Metabolic Diseases