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

Obesity Clinical Trial

Official title:

Effect of Weight Loss on Myocardial Oxygen Consumption and Left Ventricular Relaxation in Obese Adults

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00572624
• Other study ID #: 05-0523 (201105066)
• Secondary ID: P01HL013851-43
• Status: Completed
• Phase: N/A
• First received: December 12, 2007
• Last updated: May 8, 2017
• Start date: June 2003
• Est. completion date: June 2014

Study information

• Verified date: May 2017
• Source: Washington University School of Medicine
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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')).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 51
• Est. completion date: June 2014
• Est. primary completion date: June 2014
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 21 Years to 50 Years

Eligibility

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

Related Conditions & MeSH terms

• Obesity
• Weight Loss

Intervention

Behavioral:
• Diet
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.

Procedure:
• Gastric bypass surgery
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.

Locations

Country	Name	City	State
United States	Washington University Medical School	Saint Louis	Missouri

Sponsors (2)

Lead Sponsor	Collaborator
Washington University School of Medicine	National Heart, Lung, and Blood Institute (NHLBI)

Country where clinical trial is conducted

United States, 

References & Publications (5)

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. — View 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. — View 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. — View 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. — View Citation

Lin CH, Kurup S, Herrero P, Schechtman KB, Eagon JC, Klein S, Dávila-Román 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 — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	Measured at baseline, 16 months after gastric bypass surgery-induced weight loss, and 8 months after diet-induced weight loss
Primary	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.	Measured at baseline, 16 months after gastric bypass surgery-induced weight loss, and 8 months after diet-induced weight loss
Primary	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.	Measured at baseline, 16 months after gastric bypass surgery-induced weight loss, and 8 months after diet-induced weight loss
Secondary	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.	Measured at baseline, 16 months after gastric bypass surgery-induced weight loss, and 8 months after diet-induced weight loss
Secondary	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.	Measured at baseline, 16 months after gastric bypass surgery-induced weight loss, and 8 months after diet-induced weight loss
Secondary	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.	Measured at baseline, 16 months after gastric bypass surgery-induced weight loss, and 8 months after diet-induced weight loss
Secondary	Mean Heart Rate	Heart rate was measured at scheduled physical examinations.	Measured at baseline, 16 months after gastric bypass surgery-induced weight loss, and 8 months after diet-induced weight loss
Secondary	Mean Arterial Pressure	Mean arterial pressure was measured at scheduled physical examinations.	Measured at baseline, 16 months after gastric bypass surgery-induced weight loss, and 8 months after diet-induced weight loss
Secondary	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.	Measured at baseline, 16 months after gastric bypass surgery-induced weight loss, and 8 months after diet-induced weight loss
Secondary	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).	Measured at baseline, 16 months after gastric bypass surgery-induced weight loss, and 8 months after diet-induced weight loss
Secondary	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.	Measured at baseline, 16 months after gastric bypass surgery-induced weight loss, and 8 months after diet-induced weight loss