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Effect of Weight Loss on Myocardial Metabolism and Cardiac Relaxation in Obese Adults

Primary Purpose

Obesity

Status
Completed
Phase
Not Applicable
Locations
United States
Study Type
Interventional
Intervention
Diet
Gastric bypass surgery
Sponsored by
Washington University School of Medicine
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional basic science trial for Obesity focused on measuring Heart Metabolism, Obesity, Weight loss, Gastric bypass surgery, Diet and exercise

Eligibility Criteria

21 Years - 50 Years (Adult)All SexesAccepts Healthy Volunteers

Inclusion Criteria:

  • Body mass index (BMI) > 30 kg/m^2
  • Sedentary lifestyle

Exclusion Criteria:

  • Body weight >159 kg
  • Insulin-requiring diabetes
  • Heart failure
  • History of coronary artery disease
  • Chest pain
  • Untreated sleep apnea
  • Being an active smoker
  • Pregnant, lactating, or postmenopausal

Sites / Locations

  • Washington University Medical School

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

Diet

Gastric bypass surgery

Arm Description

Participants who received counseling and instruction about weight loss through diet and exercise

Participants who received gastric bypass surgery

Outcomes

Primary Outcome Measures

Total Myocardial Oxygen Consumption (MVO2)
The evening before an imaging study, all participants were given a meal containing 12 kcal/kg adjusted body weight (=ideal body weight + ((actual body weight-ideal body weight) x 0.25)). Participants fasted until their imaging studies were completed. Myocardial oxygen consumption (MVO2) was measured using positron emission tomography (PET) following injection of 1-^11C-acetate. Total MVO2 was calculated by multiplying the MVO2 measure by left ventricular weight.
Total Myocardial Fatty Acid (FA) Utilization
The evening before an imaging study, all participants were given a meal containing 12 kcal/kg adjusted body weight (=ideal body weight + ((actual body weight-ideal body weight) x 0.25)). Participants fasted until their imaging studies were completed. Myocardial blood flow was measured using positron emission tomography (PET) following injection of ^30O-water. Myocardial fatty acid (FA) utilization was measured using PET after injection of 1-^11C-palmitate. The calculations that describe the relationship between the different measures of myocardial FA metabolism are: FA utilization/gram = blood flow/gram × FA uptake/gram × [average plasma free FA at the time of the 1-11C-palmitate injection]; FA utilization/gram = FA oxidation/gram + esterification/gram. Total fatty acid utilization was calculated by multiplying the fatty acid utilization rate by left ventricular weight.
Total Myocardial Fatty Acid (FA) Oxidation
The evening before an imaging study, all participants were given a meal containing 12 kcal/kg adjusted body weight (=ideal body weight + ((actual body weight-ideal body weight) x 0.25)). Participants fasted until their imaging studies were completed. Myocardial fatty acid utilization was measured using positron emission tomography (PET) after injecting 1-^11C-palmitate. Total fatty acid oxidation was calculated by multiplying the fatty acid oxidation rate by left ventricular weight.

Secondary Outcome Measures

Left Ventricular (LV) Relaxation (E')
Immediately following MVO2 measurement, complete two-dimensional, M-mode, and Doppler echocardiographic studies were performed using second harmonic imaging. Left ventricular relaxation (E') was measured at the lateral annulus. All reported measurements represent the average of three consecutive cardiac cycles. A single investigator blinded to all clinical parameters evaluated all echocardiograms.
Septal Ratio (E/E')
Immediately following MVO2 measurement, complete two-dimensional, M-mode, and Doppler echocardiographic studies were performed using second harmonic imaging. The early diastolic (E) velocity was measured, left ventricular relaxation (E') was measured at the lateral mitral annulus, and the E/E'(septal) ratio was calculated. All reported measurements represent the average of three consecutive cardiac cycles. A single investigator blinded to all clinical parameters evaluated all echocardiograms. The normal septal ratio from the lateral mitral annulus is <5, a ratio from 5 to 10 is indeterminate, and a ratio of >10 indicates elevated left atrial pressure.
Left Ventricular (LV) Mass
Immediately following MVO2 measurement, complete two-dimensional, M-mode, and Doppler echocardiographic study were performed using second harmonic imaging. Left ventricular (LV) mass was measured using the area-length method. All reported measurements represent the average of three consecutive cardiac cycles. A single investigator blinded to all clinical parameters evaluated all echocardiograms.
Mean Heart Rate
Heart rate was measured at scheduled physical examinations.
Mean Arterial Pressure
Mean arterial pressure was measured at scheduled physical examinations.
Mean Body Mass Index
Participant weight and height was measured at scheduled physical examinations. Body mass index was calculated as participant body weight in kilograms divided by their height in meters squared.
Mean Total Serum Cholesterol and Triglycerides
Blood testing was conducted at scheduled times during the study. Serum cholesterol and triglycerides were measured by the enzymatic method (Roche Diagnostics).
Mean Homeostasis Model Assessment of Insulin Resistance
The homeostasis model assessment of insulin resistance (HOMA) was used to calculate insulin resistance using the first AM, fasting glucose and insulin levels. Plasma insulin levels were measured by radioimmunoassay, and glucose levels were measured by automated hexokinase assay. A HOMA score of <3 represents normal insulin resistance, a score between 3 and 5 moderate insulin resistance, and a score of 5 or higher represents severe insulin resistance.

Full Information

First Posted
December 12, 2007
Last Updated
May 8, 2017
Sponsor
Washington University School of Medicine
Collaborators
National Heart, Lung, and Blood Institute (NHLBI)
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1. Study Identification

Unique Protocol Identification Number
NCT00572624
Brief Title
Effect of Weight Loss on Myocardial Metabolism and Cardiac Relaxation in Obese Adults
Official Title
Effect of Weight Loss on Myocardial Oxygen Consumption and Left Ventricular Relaxation in Obese Adults
Study Type
Interventional

2. Study Status

Record Verification Date
May 2017
Overall Recruitment Status
Completed
Study Start Date
June 2003 (undefined)
Primary Completion Date
June 2014 (Actual)
Study Completion Date
June 2014 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Washington University School of Medicine
Collaborators
National Heart, Lung, and Blood Institute (NHLBI)

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief Summary
Obesity adversely affects myocardial (muscular heart tissue) metabolism, efficiency, and diastolic function. The objective of this study was to determine if weight loss could improve obesity-related myocardial metabolism and efficiency and if these improvements were directly related to improved diastolic function.
Detailed Description
This was a prospective, interventional study in obese adults ages 21 to 50 years of age to determine whether weight loss could improve obesity-related myocardial metabolism and efficiency. Two different mechanisms of weight loss were studied: diet and exercise and gastric bypass surgery. Positron emission tomography (PET) was used to quantitate myocardial oxygen consumption (MVO2) and myocardial fatty acid (FA) metabolism. Echocardiography with tissue Doppler imaging was used to quantify cardiac structure, systolic and diastolic function (left ventricular (LV) relaxation (E') and septal ratio (E/E')).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Obesity
Keywords
Heart Metabolism, Obesity, Weight loss, Gastric bypass surgery, Diet and exercise

7. Study Design

Primary Purpose
Basic Science
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
51 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Diet
Arm Type
Experimental
Arm Description
Participants who received counseling and instruction about weight loss through diet and exercise
Arm Title
Gastric bypass surgery
Arm Type
Experimental
Arm Description
Participants who received gastric bypass surgery
Intervention Type
Behavioral
Intervention Name(s)
Diet
Intervention Description
Participants attended 20 group behavioral modification sessions led by a behaviorist, a registered dietician, and a physical therapist. The meal plans ranged from 1200 to 1500 kilocalories per day, depending on subject sex and BMI, and were designed to achieve ≤1% body weight loss/week. Participants completed daily food records, and were taught a variety of weight management skills. The exercise component included strength, flexibility, balance, and endurance instruction, gradually increasing to 30 minutes of exercise 5 days/week.
Intervention Type
Procedure
Intervention Name(s)
Gastric bypass surgery
Intervention Description
The same surgeon performed all bypass procedures using standard techniques. A small (~20 ml) proximal gastric pouch was created by stapling the stomach, and a 75-cm Roux-en-Y limb was constructed by transecting the jejunum distal to the ligament of Treitz, and creating a jejunojejunostomy 75 cm distal to the transection.
Primary Outcome Measure Information:
Title
Total Myocardial Oxygen Consumption (MVO2)
Description
The evening before an imaging study, all participants were given a meal containing 12 kcal/kg adjusted body weight (=ideal body weight + ((actual body weight-ideal body weight) x 0.25)). Participants fasted until their imaging studies were completed. Myocardial oxygen consumption (MVO2) was measured using positron emission tomography (PET) following injection of 1-^11C-acetate. Total MVO2 was calculated by multiplying the MVO2 measure by left ventricular weight.
Time Frame
Measured at baseline, 16 months after gastric bypass surgery-induced weight loss, and 8 months after diet-induced weight loss
Title
Total Myocardial Fatty Acid (FA) Utilization
Description
The evening before an imaging study, all participants were given a meal containing 12 kcal/kg adjusted body weight (=ideal body weight + ((actual body weight-ideal body weight) x 0.25)). Participants fasted until their imaging studies were completed. Myocardial blood flow was measured using positron emission tomography (PET) following injection of ^30O-water. Myocardial fatty acid (FA) utilization was measured using PET after injection of 1-^11C-palmitate. The calculations that describe the relationship between the different measures of myocardial FA metabolism are: FA utilization/gram = blood flow/gram × FA uptake/gram × [average plasma free FA at the time of the 1-11C-palmitate injection]; FA utilization/gram = FA oxidation/gram + esterification/gram. Total fatty acid utilization was calculated by multiplying the fatty acid utilization rate by left ventricular weight.
Time Frame
Measured at baseline, 16 months after gastric bypass surgery-induced weight loss, and 8 months after diet-induced weight loss
Title
Total Myocardial Fatty Acid (FA) Oxidation
Description
The evening before an imaging study, all participants were given a meal containing 12 kcal/kg adjusted body weight (=ideal body weight + ((actual body weight-ideal body weight) x 0.25)). Participants fasted until their imaging studies were completed. Myocardial fatty acid utilization was measured using positron emission tomography (PET) after injecting 1-^11C-palmitate. Total fatty acid oxidation was calculated by multiplying the fatty acid oxidation rate by left ventricular weight.
Time Frame
Measured at baseline, 16 months after gastric bypass surgery-induced weight loss, and 8 months after diet-induced weight loss
Secondary Outcome Measure Information:
Title
Left Ventricular (LV) Relaxation (E')
Description
Immediately following MVO2 measurement, complete two-dimensional, M-mode, and Doppler echocardiographic studies were performed using second harmonic imaging. Left ventricular relaxation (E') was measured at the lateral annulus. All reported measurements represent the average of three consecutive cardiac cycles. A single investigator blinded to all clinical parameters evaluated all echocardiograms.
Time Frame
Measured at baseline, 16 months after gastric bypass surgery-induced weight loss, and 8 months after diet-induced weight loss
Title
Septal Ratio (E/E')
Description
Immediately following MVO2 measurement, complete two-dimensional, M-mode, and Doppler echocardiographic studies were performed using second harmonic imaging. The early diastolic (E) velocity was measured, left ventricular relaxation (E') was measured at the lateral mitral annulus, and the E/E'(septal) ratio was calculated. All reported measurements represent the average of three consecutive cardiac cycles. A single investigator blinded to all clinical parameters evaluated all echocardiograms. The normal septal ratio from the lateral mitral annulus is <5, a ratio from 5 to 10 is indeterminate, and a ratio of >10 indicates elevated left atrial pressure.
Time Frame
Measured at baseline, 16 months after gastric bypass surgery-induced weight loss, and 8 months after diet-induced weight loss
Title
Left Ventricular (LV) Mass
Description
Immediately following MVO2 measurement, complete two-dimensional, M-mode, and Doppler echocardiographic study were performed using second harmonic imaging. Left ventricular (LV) mass was measured using the area-length method. All reported measurements represent the average of three consecutive cardiac cycles. A single investigator blinded to all clinical parameters evaluated all echocardiograms.
Time Frame
Measured at baseline, 16 months after gastric bypass surgery-induced weight loss, and 8 months after diet-induced weight loss
Title
Mean Heart Rate
Description
Heart rate was measured at scheduled physical examinations.
Time Frame
Measured at baseline, 16 months after gastric bypass surgery-induced weight loss, and 8 months after diet-induced weight loss
Title
Mean Arterial Pressure
Description
Mean arterial pressure was measured at scheduled physical examinations.
Time Frame
Measured at baseline, 16 months after gastric bypass surgery-induced weight loss, and 8 months after diet-induced weight loss
Title
Mean Body Mass Index
Description
Participant weight and height was measured at scheduled physical examinations. Body mass index was calculated as participant body weight in kilograms divided by their height in meters squared.
Time Frame
Measured at baseline, 16 months after gastric bypass surgery-induced weight loss, and 8 months after diet-induced weight loss
Title
Mean Total Serum Cholesterol and Triglycerides
Description
Blood testing was conducted at scheduled times during the study. Serum cholesterol and triglycerides were measured by the enzymatic method (Roche Diagnostics).
Time Frame
Measured at baseline, 16 months after gastric bypass surgery-induced weight loss, and 8 months after diet-induced weight loss
Title
Mean Homeostasis Model Assessment of Insulin Resistance
Description
The homeostasis model assessment of insulin resistance (HOMA) was used to calculate insulin resistance using the first AM, fasting glucose and insulin levels. Plasma insulin levels were measured by radioimmunoassay, and glucose levels were measured by automated hexokinase assay. A HOMA score of <3 represents normal insulin resistance, a score between 3 and 5 moderate insulin resistance, and a score of 5 or higher represents severe insulin resistance.
Time Frame
Measured at baseline, 16 months after gastric bypass surgery-induced weight loss, and 8 months after diet-induced weight loss

10. Eligibility

Sex
All
Minimum Age & Unit of Time
21 Years
Maximum Age & Unit of Time
50 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria: Body mass index (BMI) > 30 kg/m^2 Sedentary lifestyle Exclusion Criteria: Body weight >159 kg Insulin-requiring diabetes Heart failure History of coronary artery disease Chest pain Untreated sleep apnea Being an active smoker Pregnant, lactating, or postmenopausal
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Robert Gropler, MD
Organizational Affiliation
Washington University Medical School
Official's Role
Principal Investigator
Facility Information:
Facility Name
Washington University Medical School
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63110
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
PubMed Identifier
10546692
Citation
Allison DB, Fontaine KR, Manson JE, Stevens J, VanItallie TB. Annual deaths attributable to obesity in the United States. JAMA. 1999 Oct 27;282(16):1530-8. doi: 10.1001/jama.282.16.1530.
Results Reference
background
PubMed Identifier
10954760
Citation
Hu FB, Stampfer MJ, Manson JE, Grodstein F, Colditz GA, Speizer FE, Willett WC. Trends in the incidence of coronary heart disease and changes in diet and lifestyle in women. N Engl J Med. 2000 Aug 24;343(8):530-7. doi: 10.1056/NEJM200008243430802.
Results Reference
background
PubMed Identifier
2339449
Citation
Folsom AR, Prineas RJ, Kaye SA, Munger RG. Incidence of hypertension and stroke in relation to body fat distribution and other risk factors in older women. Stroke. 1990 May;21(5):701-6. doi: 10.1161/01.str.21.5.701.
Results Reference
background
PubMed Identifier
9098178
Citation
Carey VJ, Walters EE, Colditz GA, Solomon CG, Willett WC, Rosner BA, Speizer FE, Manson JE. Body fat distribution and risk of non-insulin-dependent diabetes mellitus in women. The Nurses' Health Study. Am J Epidemiol. 1997 Apr 1;145(7):614-9. doi: 10.1093/oxfordjournals.aje.a009158.
Results Reference
background
PubMed Identifier
21738241
Citation
Lin CH, Kurup S, Herrero P, Schechtman KB, Eagon JC, Klein S, Davila-Roman VG, Stein RI, Dorn GW 2nd, Gropler RJ, Waggoner AD, Peterson LR. Myocardial oxygen consumption change predicts left ventricular relaxation improvement in obese humans after weight loss. Obesity (Silver Spring). 2011 Sep;19(9):1804-12. doi: 10.1038/oby.2011.186. Epub 2011 Jul 7.
Results Reference
result
PubMed Identifier
21818149
Citation
Peterson LR, Saeed IM, McGill JB, Herrero P, Schechtman KB, Gunawardena R, Recklein CL, Coggan AR, DeMoss AJ, Dence CS, Gropler RJ. Sex and type 2 diabetes: obesity-independent effects on left ventricular substrate metabolism and relaxation in humans. Obesity (Silver Spring). 2012 Apr;20(4):802-10. doi: 10.1038/oby.2011.208. Epub 2011 Aug 4.
Results Reference
derived

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Effect of Weight Loss on Myocardial Metabolism and Cardiac Relaxation in Obese Adults

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