CClinicalTrials.gg
CompletedNCT03448185MTGUpdated Jan 5, 2023Results posted

Improving Metabolic Health in Patients With Diastolic Dysfunction

An interventional study of High intensity exercise and Omega-3 fish oil in Obesity, Heart Failure, Diastolic and Metabolic Syndrome, sponsored by University of Texas Southwestern Medical Center. Completed at 1 site in United States. Open to participants aged 40 Years to 60 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2023-01-05.

Sponsored by University of Texas Southwestern Medical Center · Not applicable, Interventional, and Treatment

Phase
Not applicable
Study type
Interventional
Enrollment
80
Allocation
Randomized
Ages
40 Years to 60 Years
Sex
All
01

Study 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.

Read the 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.

02

Conditions studied

  • Obesity
  • Heart Failure, Diastolic
  • Metabolic Syndrome
03

Who can participate

Ages eligible
40 Years to 60 Years
Sexes eligible
All
Accepts healthy volunteers
Yes

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 (>0.6pg/ml), or NTBNP (>40 ng/ml)
  4. age range 40 -60
  5. BMI range 30 - 50 kg/m2

Exclusion criteria

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
04

Study design

Phase
Not applicable
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Factorial assignment
Masking
Triple (Participant, Investigator, Outcomes assessor)
Enrollment
80 participants (actual)

Study arms

  • Placebo comparator
    Control

    Subjects randomized to control group will receive olive oil placebo capsules and yoga intervention for 1 year.

    Behavioral: Yoga · Dietary Supplement: olive oil capsules

  • 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 · Dietary Supplement: Omega-3 fish oil

  • 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 · Behavioral: Yoga

  • Active comparator
    Exercise control

    Subjects will receive olive oil placebo as well as aerobic exercise intervention for 1 year.

    Behavioral: High intensity exercise · Dietary Supplement: olive oil capsules

Interventions

  • BehavioralHigh 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 supplementOmega-3 fish oil

    Subjects randomized to omega-3 fatty acids will take 2 grams total of omega-3 per day for 1 year.

  • BehavioralYoga

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

  • Dietary supplementolive oil capsules

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

05

What researchers measure

Primary outcomes

  1. Change From Baseline at 1 Year in Myocardial Lipid Content

    Myocardial triglyceride (lipid) content will be measured using cardiac nuclear magnetic resonance spectroscopy. We quantified the total myocardial triglyceride (TG) resonance from water-suppressed spectra. Myocardial TG content relative to water (%) as well as relative amounts of myocardial TG was calculated from the available data.

    Time frame: Baseline, 1 year

Secondary outcomes

  1. Change From Baseline at 1 Year in Peak Volume of Oxygen (VO2)

    Change in peak VO2 (normalized for body weight those who completed the study). Peak VO2 is a measure how well the heart and lungs are working during exercise.

    Time frame: Baseline,1 year

  2. Change From Baseline at 1 Year in Markers of Arterial Stiffness

    Changes in arterial stiffness is measured using pulse-wave velocity (PWV) to look at intervention effects from baseline to 1 year in the control and treatment groups.

    Time frame: Baseline, 1 year

  3. Change From Baseline at 1 Year in Left Ventricular Mass

    Change in left ventricular mass is measured by cardiac MRI to look at intervention effects from baseline to 1 year in the control and treatment groups.

    Time frame: Baseline, 1 year

06

Results

Posted Jan 5, 2023

Participant flow

Participant flow — Overall Study
MilestoneControlExercise and Omega-3 Fatty AcidsYoga and Omega-3 Fatty AcidsExercise Control
Started16241822
Completed13131416
Not completed31146

Outcome measures

PrimaryChange From Baseline at 1 Year in Myocardial Lipid Content

Myocardial triglyceride (lipid) content will be measured using cardiac nuclear magnetic resonance spectroscopy. We quantified the total myocardial triglyceride (TG) resonance from water-suppressed spectra. Myocardial TG content relative to water (%) as well as relative amounts of myocardial TG was calculated from the available data.

Time frame:
Baseline, 1 year
Reported as:
Mean · %fat/water
Change From Baseline at 1 Year in Myocardial Lipid Content
%fat/waterControlExercise and Omega-3 Fatty AcidsYoga and Omega-3 Fatty AcidsExercise Control
Change From Baseline at 1 Year in Myocardial Lipid Content-0.16 ± 1.1-0.18 ± 0.59-0.53 ± 0.66-0.19 ± 0.42
SecondaryChange From Baseline at 1 Year in Peak Volume of Oxygen (VO2)

Change in peak VO2 (normalized for body weight those who completed the study). Peak VO2 is a measure how well the heart and lungs are working during exercise.

Time frame:
Baseline,1 year
Reported as:
Mean · ml/kg/min
Change From Baseline at 1 Year in Peak Volume of Oxygen (VO2)
ml/kg/minControlExercise and Omega-3 Fatty AcidsYoga and Omega-3 Fatty AcidsExercise Control
Change From Baseline at 1 Year in Peak Volume of Oxygen (VO2)0.21 ± 1.594.39 ± 2.48-0.03 ± 1.844.53 ± 2.65
SecondaryChange From Baseline at 1 Year in Markers of Arterial Stiffness

Changes in arterial stiffness is measured using pulse-wave velocity (PWV) to look at intervention effects from baseline to 1 year in the control and treatment groups.

Time frame:
Baseline, 1 year
Reported as:
Mean · cm/s
Change From Baseline at 1 Year in Markers of Arterial Stiffness
cm/sControlExercise and Omega-3 Fatty AcidsYoga and Omega-3 Fatty AcidsExercise Control
Change From Baseline at 1 Year in Markers of Arterial Stiffness-15 ± 107-16 ± 8032 ± 141-7 ± 104
SecondaryChange From Baseline at 1 Year in Left Ventricular Mass

Change in left ventricular mass is measured by cardiac MRI to look at intervention effects from baseline to 1 year in the control and treatment groups.

Time frame:
Baseline, 1 year
Reported as:
Mean · grams
Change From Baseline at 1 Year in Left Ventricular Mass
gramsControlExercise and Omega-3 Fatty AcidsYoga and Omega-3 Fatty AcidsExercise Control
Change From Baseline at 1 Year in Left Ventricular Mass0.2 ± 7.77.2 ± 6.6-5.8 ± 10.46.0 ± 10

Adverse events

Collected over 1 year, during study period. Non-serious events are listed at a 0% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Control0/13 (0%)0/13 (0%)0/13 (0%)
Exercise and Omega-3 Fatty Acids0/13 (0%)0/13 (0%)0/13 (0%)
Yoga and Omega-3 Fatty Acids0/14 (0%)0/14 (0%)0/14 (0%)
Exercise Control0/16 (0%)0/16 (0%)0/16 (0%)

Baseline characteristics

Age, Continuous
Age, Continuous(years)ControlExercise and Omega-3 Fatty AcidsYoga and Omega-3 Fatty AcidsExercise ControlTotal
Mean49 ± 650 ± 647 ± 950 ± 649 ± 6
Sex: Female, Male
Sex: Female, Male(Participants)ControlExercise and Omega-3 Fatty AcidsYoga and Omega-3 Fatty AcidsExercise ControlTotal
Female1115101248
Male5981032
Race (NIH/OMB)
Race (NIH/OMB)(Participants)ControlExercise and Omega-3 Fatty AcidsYoga and Omega-3 Fatty AcidsExercise ControlTotal
American Indian or Alaska Native11002
Asian00112
Native Hawaiian or Other Pacific Islander00000
Black or African American356317
White1218111859
More than one race00000
Unknown or Not Reported00000
BMI
BMI(kg/m^2)ControlExercise and Omega-3 Fatty AcidsYoga and Omega-3 Fatty AcidsExercise ControlTotal
Mean36.7 ± 5.236.7 ± 5.340.5 ± 6.536.7 ± 5.038.9 ± 5.7
07

Study locations

1 site
  • The Institute for Exercise and Environmental Medicine
    Dallas, Texas 75231, United States
08

References and documents

Publications

  • Hearon CM Jr, Dias KA, MacNamara JP, Hieda M, Mantha Y, Harada R, Samels M, Morris M, Szczepaniak LS, Levine BD, Sarma S. 1 Year HIIT and Omega-3 Fatty Acids to Improve Cardiometabolic Risk in Stage-A Heart Failure. JACC Heart Fail. 2022 Apr;10(4):238-249. doi: 10.1016/j.jchf.2022.01.004. Epub 2022 Mar 9. PubMed 35361442 ↗

Study documents

  • Study protocol · Apr 8, 2016
  • Statistical analysis plan · Jan 6, 2014
  • Informed consent form · Jul 6, 2017

Documents are hosted by the registry — open the source record to download them.

Individual participant data

Plan to share: No

09

Registry details

Key details

Study ID
NCT03448185
Lead sponsor
University of Texas Southwestern Medical Center
Responsible party
Satyam Sarma (ASSISTANT PROFESSOR, University of Texas Southwestern Medical Center) — Principal investigator
First posted
Feb 27, 2018
Start date
Jun 1, 2015
Primary completion
Jul 1, 2019
Completion
Jul 1, 2019
Results posted
Jan 5, 2023
Last update
Jan 5, 2023

Study contacts

Benjamin D Levine, MD
study director · University of Texas Southwestern Medical Center

Oversight

Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

Not currently enrolling

This study is completed, as verified in Apr 2022. You cannot join it, but the record below documents what was studied.

Follow this study

Get an email when the registry record changes — status, dates, results — or when someone posts here.

Sign in to follow

Discussion

Questions and observations about this study, from anyone following it. Not medical advice, and not a channel to the study team — their contact details are on the registry record.

Sign in to join the discussion. Reading takes no account; posting does. You choose a display name, and a pseudonym is the default.

Nothing here yet. If you are running this trial, taking part in it, or weighing whether to, this is the place to say so.

Start the discussion