Exercise Following Bariatric Surgery for Severe/Morbid Obesity (EFIBAR)

Study Overview
=================
Brief Summary
-----------------
Severe/morbid obesity is an international public health issue that importantly increases the risk of cardiovascular events and cardiovascular and all-cause mortality. Likewise, severe/morbid obesity increases the risk of illness, reduces quality of life, and raises health-care costs. Bariatric surgery is the election method for the treatment of severe/morbid obesity, resulting in significant weight loss and remission of comorbidities. However, a relatively large proportion of bariatric patients regain weight and continue to be at high risk for cardiovascular disease and premature mortality. A healthy lifestyle following bariatric surgery is essential for optimizing and maintaining weight loss. Observational studies suggest that physical activity following bariatric surgery might be associated with additional weight loss and more effective weigh loss maintenance over time. However, very little experimental evidence exists regarding the effects of supervised exercise on obesity-related outcomes in this specific population. The aim of the EFIBAR (Ejercicio FÍsico tras cirugía BARiátrica) randomized controlled trial is to determine the effects of a 16-week supervised concurrent (aerobic and strength) exercise intervention program, on weight loss (primary outcome), body composition, cardiometabolic risk, physical fitness and quality of life (secondary outcomes) in patients with severe/morbid obesity following bariatric surgery. According to the study aims the investigators pursue the following hypothesis: Supervised exercise will result in larger weight loss than control.

Official Title
-----------------
Supervised Exercise Following Bariatric Surgery in the Treatment of Severe/Morbid Obesity: a Randomized Controlled Trial

Conditions
-----------------
Obesity, Morbid, Bariatric Surgery Candidate

Intervention / Treatment
-----------------
* Other: Exercise


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: To comply with local bariatric surgery criteria: Patients with BMI ≥ 40 kg/m2 (or 35 kg/m2 with comorbidities). Acceptable surgical risk (defined by the approval of anesthetist). Obesity maintained for over 5 years. Failure of previous treatments. To sign informed consent for surgical treatment. Not to present contraindications for supervised physical exercise. To reside in the city of Almeria (Spain) or willingness/predisposition to attend the training sessions 3 times a week during 16 weeks Exclusion Criteria: Severe psychiatric or neurological disorders such as schizophrenia, epilepsia, Alzheimer, Parkinson, personality disorders, eating behaviour disorders, untreated depression or suicidal tendencies. Adrenal or thyroid pathology that might cause obesity. Uncontrolled addiction to alcohol or drugs.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 60 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Eligible participants will be randomly assigned (1:1) sequentially, as they will be submitted to bariatric surgery, to one of the two following groups: CON - Usual care (following international guidelines) after bariatric surgery. EX - Usual care plus supervised exercise program.
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Exercise<br>Usual care PLUS concurrent (aerobic and strength) supervised exercise program of 16 weeks (3 sessions/week, 60 min/session, progressively increasing in volume and intensity). The program will be conducted by certified Exercise Science professionals. | Other: Exercise<br>* Concurrent (aerobic and strength) supervised exercise program: the program comprises 3 sessions/week (60 min/session) of aerobic and strength exercises of progressive volume and intensity. The program will follow the Consensus on Exercise Reporting Template (CERT) guidelines.<br>* Other names: Exercise training;|
| No Intervention: Control<br>Usual care routinely delivered after bariatric surgery, based on national (Spanish) and international recommendations, focused on nutritional status monitoring and diet/physical activity counseling. | |

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent total weight loss (%TWL) [Biospace Co., InBody 270, USA] | %TWL = [(pre-surgery weight - post-surgery weight) / (pre-surgery weight)] x 100 | Changes from baseline to 4-month and 1-year follow-up | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Body composition: body fat | Percent body fat (%) assessed by bioimpedance analysis (InBody 270, Biospace Co., USA) | Changes from baseline to 4-month and 1-year follow-up | 
| Body composition: fat-free mass | Fat-free mass (kg) assessed by bioimpedance analysis (InBody 270, Biospace Co., USA) | Changes from baseline to 4-month and 1-year follow-up | 
| Body composition: fat-free mass index | Fat-free mass index (kg/m2) assessed by bioimpedance analysis (InBody 270, Biospace Co., USA) | Changes from baseline to 4-month and 1-year follow-up | 
| Body composition: central body fat | Waist and hip circumferences (measured in cm with an anthropometric tape), waist / height ratio | Changes from baseline to 4-month and 1-year follow-up | 
| Lipid profile assessed from blood sample | Total cholesterol (mg/dl), HDL-cholesterol (mg/dl), LDL-cholesterol (mg/dl) and triglycerides (mg/dl) | Changes from baseline to 4-month and 1-year follow-up | 
| Blood markers of glucose metabolism: glucose | Glucose (mg/dL) | Changes from baseline to 4-month and 1-year follow-up | 
| Blood markers of glucose metabolism: insulin | Insulin (μUI/mL) | Changes from baseline to 4-month and 1-year follow-up | 
| Blood markers of glucose metabolism: HOMA-IR | Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) | Changes from baseline to 4-month and 1-year follow-up | 
| Blood markers of glucose metabolism: glycated hemoglobin HbA1c | Glycated hemoglobin HbA1c (%) | Changes from baseline to 4-month and 1-year follow-up | 
| Brachial and central blood pressures (mmHg) | Systolic and diastolic blood pressures assessed by Mobil-O-Graph | Changes from baseline to 4-month and 1-year follow-up | 
| Arterial stiffness | Pulse wave velocity (PWV, m/s) by Mobil-O-Graph | Changes from baseline to 4-month and 1-year follow-up | 
| Plasma concentrations of inflammatory markers | High-sensitivity C-reactive protein (hs-CRP) | Changes from baseline to 4-month and 1-year follow-up | 
| Plasma concentrations of inflammatory markers | Tumor necrosis factor (TNF-alpha) | Changes from baseline to 4-month and 1-year follow-up | 
| Plasma concentrations of inflammatory markers | Interleukin 6 (IL-6) | Changes from baseline to 4-month and 1-year follow-up | 
| Plasma concentrations of liver metabolism enzymes | GGT (gamma-glutamyltransferase) | Changes from baseline to 4-month and 1-year follow-up | 
| Plasma concentrations of liver metabolism enzymes | GPT (glutamate-pyruvate transaminase) | Changes from baseline to 4-month and 1-year follow-up | 
| Plasma concentrations of liver metabolism enzymes | GOT (glutamate-oxalacetate transaminase) | Changes from baseline to 4-month and 1-year follow-up | 
| Plasma levels of Vitamin D | Concentrations of 25-hydroxyvitamin D (ng/mL) | Changes from baseline to 4-month and 1-year follow-up | 
| Heart rate variability (HRV) | Assessed by heart rate monitor (Polar V800) | Changes from baseline to 4-month and 1-year follow-up | 
| Health-related physical fitness: cardiorespiratory fitness | Cardiorespiratory fitness, assessed using a maximal treadmill test | Changes from baseline to 4-month and and 1-year follow-up | 
| Health-related physical fitness: upper body muscular strength | Upper body muscular strength, assessed using handgrip dynamometry (kg) | Changes from baseline to 4-month and and 1-year follow-up | 
| Health-related physical fitness: lower body muscular strength | Lower body muscular strength, assessed using the 30-seconds chair-stand test (number of repetitions) | Changes from baseline to 4-month and and 1-year follow-up | 
| Health-related physical fitness: upper body flexibility | Upper body flexibility, assessed using the back scratch test (cm) | Changes from baseline to 4-month and and 1-year follow-up | 
| Objectively-measured physical activity | Assessed by accelerometry (ActiGraph, software ActiLife) | Changes from baseline to 4-month and 1-year follow-up | 
| Health-Related Quality of Life (HRQoL): SF-36 | Measured by the 36-item Short Form Health Survey (SF-36) | Changes from baseline to 4-month and 1-year follow-up | 
| Health-Related Quality of Life (HRQoL): EQ-5D-3L | Measured by European Quality of Life - 5 Dimensions-3Levels (EQ-5D-3L) | Changes from baseline to 4-month and 1-year follow-up | 
| Symptomatology and function of hip / knee osteoarthritis: Pain | Measured by the WOMAC (Western Ontario and McMaster Universities) Osteoarthritis Index. The PAIN scale within the WOMAC questionnaire contains 5 items, each one scoring from 0 (Nothing) to 4 (Very much), what makes a total score ranging from 0 (better) to 20 (worse). | Changes from baseline to 4-month and 1-year follow-up | 
| Symptomatology and function of hip / knee osteoarthritis: Function | Measured by the WOMAC (Western Ontario and McMaster Universities) Osteoarthritis Index. The FUNCTION scale within the WOMAC questionnaire contains 17 items, each one scoring from 0 (No trouble) to 4 (Very much difficult), what makes a total score ranging from 0 (better) to 68 (worse). | Changes from baseline to 4-month and 1-year follow-up | 
| Symptomatology and function of hip / knee osteoarthritis: Stiffness | Measured by the WOMAC (Western Ontario and McMaster Universities) Osteoarthritis Index. The STIFFNESS scale within the WOMAC questionnaire contains 2 items, each one scoring from 0 (Nothing) to 4 (Very much), what makes a total score ranging from 0 (better) to 8 (worse). | Changes from baseline to 4-month and 1-year follow-up | 
| Depression, anxiety and stress | Measured by the Depression, Anxiety and Stress Scale short form (DASS-21). The DASS-21 comprises three sub-scales assessing specific psychiatric symptoms (i.e., depression, anxiety, and stress). Each of these symptoms is assessed using seven items rated on a 4-point Likert-type scale (i.e., 0 = ''Did not apply to me at all''; 3 = ''Applied to me very much, or most of the time''). Summed score for each psychiatric symptom ranges from 0 to 21. Higher scores in each sub-scale indicate higher levels of depressive, anxiety or stress symptomatology. According to the specific nature of the three psychiatric symptoms assessed by the DASS-21, these are treated independently so that no total score is available. | Changes from baseline to 4-month and 1-year follow-up | 
| Emotional, psychological and social well-being | Measured by the Mental Health Continuum-Short Form (MHC-SF) | Changes from baseline to 4-month and 1-year follow-up | 
| Cost-effectiveness analysis (CEA) | The costs will consider those related to the surgery, the exercise program, prescription medication, sick leave, post-surgery complications and readmission rates, time and effort requiring each treatment, as well as possible dietary and informal care costs. Effectiveness will be considered as changes observed in the main clinical outcomes: weight loss and cardiometabolic risk (remission/relapse of hypertension, dyslipidemia and type 2 diabetes). | From baseline to 1-year follow-up | 
| Cost-utility analysis (CUA) | The costs will consider those related to the surgery, the exercise program, prescription medication, sick leave, post-surgery complications and readmission rates, time and effort requiring each treatment, as well as possible dietary and informal care costs. Utility will evaluate variation in quality of life experienced by participants, computed as changes in quality-adjusted life years (QALY) using SF-36 questionnaire. | From baseline to 1-year follow-up | 
| Cost-utility analysis (CUA) | The costs will consider those related to the surgery, the exercise program, prescription medication, sick leave, post-surgery complications and readmission rates, time and effort requiring each treatment, as well as possible dietary and informal care costs. Utility will evaluate variation in quality of life experienced by participants, computed as changes in quality-adjusted life years (QALY) using EQ-5D-3L questionnaire. | From baseline to 1-year follow-up | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Morbid obesity, Exercise, Weight loss, Cardiometabolic risk, Bariatric surgery