Effect of Gastric Bypass-induced Weight Loss on Myocardial Structure, Function and Metabolism

May 3, 2016 updated by: Washington University School of Medicine

Obesity affects more than 43 million Americans and is associated with an increased incidence of heart failure, sudden death, and cardiovascular death. We have shown that increasing obesity is independently associated with potentially detrimental LV structural and functional, and metabolic changes. Thus in order to increase our understanding of the effect of obesity on the heart, we wish to study the effect of significant weight loss on these parameters.

Study Overview

Status

Completed

Conditions

Detailed Description

Thirty obese patients who weigh <350#, the weight limit of the PET table, who are to undergo gastric bypass will be enrolled in this study. Written, informed consent approved by the Institutional Review Board of Washington University School of Medicine will be obtained from each subject before his/her participation in this study. Subjects will be compensated for their time. Subjects will undergo Medical Screening (Visit 1) consisting of a comprehensive medical evaluation: a history (questionnaire), physical examination, EKG, blood chemistries, kidney function, complete blood count, lipid profiles and pregnancy tests for women of childbearing age. Subjects who weigh < 300# will have fat-free mass (body composition) determined by using a machine called DEXA. Measurement of Insulin Resistance (Visit 2): Subjects will undergo a hyperinsulinemic/euglycemic clamp and nonradiolabeled glucose infusion in order to define their level of insulin resistance and total body glucose turnover. This study will be performed in the GCRC.

Measurement of Myocardial Metabolism, Efficiency, Structure, and Function Measures and Total Body Fatty Acid Metabolism (Visit 3): Subjects will be admitted to the GCRC the evening before the PET imaging and at 6 pm will receive a standard meal. The next morning an 18-gauge intravenous catheter will be inserted into your arm vein. A catheter (small tube) will also be placed in the radial artery for the total body fat metabolism measurements & for blood pressure monitoring. If the subject wishes it, they may have a Foley placed for urination during the PET scan studies. Myocardial PET imaging. Studies will be performed during fasting conditions at 8 am and ending at 1:00 pm. Each subject will be positioned within the scanner, and a 2-min data collection will be acquired to verify proper positioning before a 5-min. scan will be performed for generation of attenuation correction factors. Heart blood flow, oxygen consumption, and measures of fat metabolism will be obtained using PET imaging after the sequential injections of radiolabeled tracers as reported previously by our group. Blood pressure and heart rate will be monitored continuously and recorded throughout the image acquisition. During the scans, 5 blood samples (0, 2, 10, 20,& 30 min) will be obtained for measurement of hormones, heart fuels (e.g. fats, lactate) and carbon dioxide levels.

Anonymous Genetic Tissue and Data Sampling: Draw and store 1 tablespoon of subject's blood, for a period of up to 10 years, to be used in future studies for screening for differences in genes related to heart membrane proteins or heart energy metabolism (including but not limited to genes known as KV1.5, KV2.1, PPAR, FATP, ACS, PGC-1). Echocardiography: Immediately following the PET imaging for oxygen consumption determination, subjects will undergo a complete 2D-, 3D-, and Doppler echocardiographic examination. Optison or Definity, depending on availability, clinically used intravenous contrast agents may be administered to aid with the acquisition of the ultrasound images. Total body fatty acid metabolism measurements: Simultaneous with the PET imaging, the subjects will undergo an infusion of a tracer amount of nonradioactive fat for measurement of total body fat metabolism. Blood samples will be drawn at predetermined times for this measurement.

3 Months s/p Gastric Bypass Surgery (Visit 4). Blood sampling

1 Year s/p Gastric bypass Measurement of Body Composition, Blood Chemistries, Lipid Levels, and Insulin Resistance (Visits 5 and 6). After the subjects have undergone gastric bypass for clinical reasons and are weight stable for 2 weeks (after approximately 1 year post-gastric bypass).

Study Type

Observational

Enrollment (Actual)

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

United States
- Missouri
  - St. Louis, Missouri, United States, 63110
    - Washington University in St. Louis

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

Ages Eligible for Study

18 years to 55 years (Adult)

Accepts Healthy Volunteers

Genders Eligible for Study

All

Sampling Method

Non-Probability Sample

Study Population

Patients who are to undergo gastric bypass surgery

Description

Inclusion Criteria:

Subjects that will undergo gastric bypass surgery will be included in the study.

Exclusion Criteria:

Subjects who have a history of insulin-requiring diabetes, ≥Class II hypertension, cardiac disease, major systemic disease, of smoking cigarettes with in the last 12 months, who are pregnant or taking vasoactive or lipid-lowering medications will be excluded because these conditions may affect our cardiac endpoints. Subjects unable to give informed consent will be excluded. Subjects > 350# (the weight limit of the PET table) will be excluded.

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

Observational Models: Case-Crossover
Time Perspectives: Prospective

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
measure the effect of marked weight loss induced by gastric bypass surgery on myocardial metabolism, efficiency, structure, and function in morbidly obese men and women Time Frame: measure at year 5	measure at year 5

Secondary Outcome Measures

Outcome Measure	Time Frame
evaluate the relationship between changes in myocardial lipid metabolism with changes in whole-body lipid metabolism caused by weight loss Time Frame: measure at year 5	measure at year 5

Collaborators and Investigators

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

Sponsor

Washington University School of Medicine

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

July 1, 2005

Primary Completion (Actual)

May 1, 2012

Study Completion (Actual)

June 1, 2014

Study Registration Dates

First Submitted

February 10, 2009

First Submitted That Met QC Criteria