Severe Obesity: Bariatric Surgery vs. Life-Style-Intervention

Study Overview
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Brief Summary
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The purpose of this study is to investigate the effects of weight loss induced by gastric bypass surgery in comparison to a psychotherapy-enhanced lifestyle intervention on cardiopulmonary performance and quality of life in patients with morbid obesity.

Detailed Description
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Obesity is a rapidly emerging health problem and an established risk factor for cardiovascular diseases. Bariatric surgery profoundly reduces body weight and mitigates sequelae of obesity. Especially randomized trials comparing the effects of bariatric surgery to conservative treatment in concerns of cardiac function are still lacking. The randomized WAS trial compares the effects of Roux-en-Y gastric bypass (RYGB) versus psychotherapy-supported lifestyle modification in morbidly obese patients. The co-primary endpoint addresses 1-year changes in cardiovascular function (peak VO2 during cardiopulmonary exercise testing) and quality of life (Short-Form-36 physical functioning scale). Prior to randomization, all included patients underwent a multimodal anti-obesity treatment for 6-12 months. Thereafter, patients were randomized and followed through month 12 to collect primary endpoints. Afterwards, patients in the lifestyle group could opt for surgery, and final visit was scheduled for all patients 24 months after randomization. The study was initially designed in 2008 as part of several interdisciplinary studies for a targeted grant and received a positive vote from the responsible ethics committee. Prior the actual start of the study in July 2011, the initial study protocol and the patient informed consent were updated and further specified. This amendment was submitted to the Ethics Committee on June 9, 2011, with a positive vote on June 30, 2011 (Amendment 1). An Amendment 2 was submitted to Ethics Committee on 08.10.2014 (positive vote 16.12.2014) to adjust randomization (previously 1:1 to the two study arms) for an unequal drop-out rate in the two study arms with higher rate in the intensified lifestyle modification. In addition, few secondary endpoints were adapted and the role of the principal investigator changed from Prof. Stefan Frantz to Prof. Martin Fassnacht.

Official Title
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Severe Obesity: Bariatric Surgery vs. Life-Style-Intervention Wurzburg Adipositas Study - WAS

Conditions
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Obesity, Cardiac Function, Quality of Life

Intervention / Treatment
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* Procedure: Roux-en-Y gastric bypass
* Behavioral: Psychotherapy-enhanced lifestyle intervention


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age ≥18 years BMI >40 kg/m2 or BMI >35 kg/m2 with severe comorbidities Indication for Roux-en-Y gastric bypass surgery Ability to perform cardiopulmonary exercise testing (CPET) Written informed consent Exclusion Criteria: Pregnancy or breast feeding Unstable angina pectoris Life expectancy <12 months Endocrine or psychiatric disorder as cause of obesity Systemic glucocorticoid treatment (with exception of glucocorticoid replacement therapy) Abuse of drugs or alcohol within the last 5 years Inability to attend regular study visits for logistic reasons Participation in competing trials

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Psychotherapy-enhanced lifestyle intervention (PELI)<br>Intensive lifestyle intervention over 12 months including medically supervised dietary counseling and physical activity enhanced by a psychotherapeutic intervention | Behavioral: Psychotherapy-enhanced lifestyle intervention<br> <br> |
| Other: Roux-en-Y-gastric bypass (RYGB)<br>Laparoscopic Roux-en-Y gastric bypass surgery | Procedure: Roux-en-Y gastric bypass<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change of peak VO2 to assess cardiorespiratory performance | Change of peak V O2 (measured in ml/min/kg bw) in cardiopulmonary exercise testing (CPET) | 12 months after surgery / lifestyle intervention | 
| Change in physical functioning scale (PFS) of the SF-36 to assess quality of life | Change of quality of life measured with physical functioning scale (PFS) of the SF-36 questionnaire (Short Form health survery 36). The score ranges from 0-100 and higher values correspond to better quality of life. | 12 months after surgery / lifestyle intervention | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in health related quality of life (other domains than physical functioning scale) | Change in quality of life (using Short Form (SF-36) health survey 36). The score ranges from 0-100 and higher values correspond to better quality of life. | 12 and 24 months after bariatric surgery / lifestyle intervention | 
| Change in left ventricular mass (index) | Assessment with echocardiography (g and g/m^2 body surface area) | 12 and 24 months after bariatric surgery / lifestyle intervention | 
| Changes in left atrial dimensions | Assessment with echocardiography (left atrial enddiastolic volume (mm^3), left atrial enddiastolic diameter (mm)) | 12 and 24 months after bariatric surgery / lifestyle intervention | 
| Changes in left ventricular dimensions | Assessment with echocardiography (left ventricular enddiastolic volume (mm^3), left ventricular enddiastolic diameter (mm)) | 12 and 24 months after bariatric surgery / lifestyle intervention | 
| Change in left ventricular systolic function | Assessment with echocardiography (left ventricular ejection fraction (%), longitudinal strain) | 12 and 24 months after bariatric surgery / lifestyle intervention | 
| Change in prevalence of left ventricular diastolic dysfunction | Assessment with echocardiography (Defined as reduced LVEF, LV hypertrophy, or LV dilation, as well as if three out of the following four criteria were fulfilled 77: LA dilation, average E/e' >14, lateral e' <0.1 m/s or septal e' <0.07 m/s, tricuspid regurgitation maximal flow velocity >2.8 m/s) | 12 and 24 months after bariatric surgery / lifestyle intervention | 
| Change in physical performance | Distance (m) achieved in the 6 minute walk test | 12 and 24 months after bariatric surgery / lifestyle intervention | 
| Change in brain morphology | Structural MRI of the brain to assess change in grey matter volume of the cerebellum (compared to normal weight controls) | 12 and 24 months after bariatric surgery / lifestyle intervention | 
| Change in brain activity | Functional MRI of the brain to assess activation to high caloric food stimuli in obese patients in insula and anterior cingulate gyrus (compared to normal weight controls) | 12 and 24 months after bariatric surgery / lifestyle intervention | 
| Change in brain oxygenation | Functional near-infrared spectroscopy (fNIRS) with assessment of frontal cortical oxygenation during Verbal Fluency Test and Trail Making Test and assessment of low frequency oscillations in resting state (in comparison to normal weight controls) | 12 and 24 months after bariatric surgery / lifestyle intervention | 
| Change in left ventricular function | Cardiac MR imaging with analysis of left ventricular function (left ventricular ejection fraction, %) | 12 and 24 months after bariatric surgery / lifestyle intervention | 
| Change in cardiac lipid content | Cardiac MR imaging with spectroscopy to measure cardiac lipid content (% fat content) | 12 and 24 months after bariatric surgery / lifestyle intervention | 
| Change in depressed mood | Assessment of depressed mood using Patient Health Questionnaire 9 (PHQ-9). The score ranges from 0-27, higher values correspond to more pronounced depressive symptoms. | 12 and 24 months after bariatric surgery / lifestyle intervention | 
| Change in depression | Assessment of depressed mood using Beck's Depression Inventory (BDI-II). The score ranges from 0-63, higher values correspond to more pronounced depressive symptoms. | 12 and 24 months after bariatric surgery / lifestyle intervention | 
| Change in liver stiffness | Assessment of liver stiffness using transient elastography (kPa) | 12 and 24 months after bariatric surgery / lifestyle intervention | 
| Change in liver triglyceride content | Assessment of liver triglyceride content with MR spectroscopy (% liver fat) | 12 and 24 months after bariatric surgery / lifestyle intervention | 
| Change in burden of comorbidities (type 2 diabetes mellitus) | Assessment of type 2 diabetes by predefined criteria. If the patient fulfils one of the following criteria, he/she would count as diabetic patient: fasting blood sugar level >= 126mg/dl, A1c => 6.5%, glucose of >=200 mg/dl 2hours in oral glucose tolerance test, or use of at least one antidiabetic medication. | 12 and 24 months after bariatric surgery / lifestyle intervention | 
| Change in burden of comorbidities (arterial hypertension) | Assessment of arterial hypertension according to predefined criteria. If the patient fulfils one of the following criteria, he/she would count as antihypertensive: systolic blood pressure >= 140mmHg, diastolic blood pressure >= 90mmHg, or use of at least one antihypertensive drug. | 12 and 24 months after bariatric surgery / lifestyle intervention | 
| Change in burden of comorbidities (dyslipidemia) | Assessment of dyslipidemia according to predefined criteria (depending on values for fasting triglycerides and ldl-cholesterol, lipid lowering medication) | 12 and 24 months after bariatric surgery / lifestyle intervention | 
| Change in NYHA functional class | Assessment of NYHA functional class (NYHA I-IV, a higher class meaning more dyspnea) | 12 and 24 months after bariatric surgery / lifestyle intervention | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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obesity, bariatric surgery, gastric bypass, life style intervention, cardiac function