Metabolic Changes After Bariatric Surgery

Study Overview
=================
Brief Summary
-----------------
Literature data clearly demonstrate that treatment of obese patients is very expensive, long and achieve weight loss may not be permanent, and regardless of whether the treatment dominated diet therapy, physical activity, or pharmacotherapy. Experience of the last decade has shown that after surgical interventional treatment of obesity occurs not only long-term (10 years and over) weight loss of 35-40%, but also an important endocrine changes. In recent years, it was discovered a number of signaling molecules produced by adipose tissue, whose physiological significance beyond the general metabolic aspects organism. The fat is therefore currently understood as an endocrine organ whose hormones modulate the function of many systems, including the skeleton. These hormones include the adipokines that modulate metabolism skeleton as at tissue level (Leptin, Adiponectin) and indirectly - by activation of neurohumoral hypothalamic centers - Leptin. Studying endocrine interactions between adipose tissue and bone is a highly topical issue. This mutual communication is a homeostatic feedback system in which adipokines and molecules secreted by osteoblasts and osteoclasts are the connecting link active axes fat - bone tissue. However, the mechanisms of this axis remain largely unknown.

Detailed Description
-----------------
Obesity is an important medical problem. The number of obese individuals is increasing continuously in response to various environmental and genetic factors. For some morbidly obese patients, surgery is the only effective type of therapy. Despite bariatric surgery having good outcomes in terms of weight loss, it is associated with some adverse effects: several studies have reported subsequent alterations in bone metabolism. Of the surgical techniques available (laparoscopic gastric banding, Roux-en-Y bypass, biliopancreatic diversion), laparoscopic sleeve gastrectomy (LSG) is currently the technique of choice. Because restrictive procedures such as LSG do not involve bypassing segments of small bowel where micronutrient absorption takes place, fewer metabolic disturbances are expected than with other surgical techniques. The observed changes in bone metabolism and status in post-bariatric surgery patients potentially involve several mechanisms, including reduced absorption of essential nutrients, diminished calcium absorption leading to secondary hyperparathyroidism, poor vitamin D absorption and restricted energy delivery. In addition, body weight protects against osteoporosis via the bone-strengthening effects of long-term weight bearing. However, long-term decreases in bone mineral density in patients who have undergone successful bariatric surgery are an unexpected, negative effect of this type of therapy. In the study, parameters of fat and bone tissue and body composition changes are assessed in groups of bariatric patients after LSG, gastric plication and intragastric balloon treatment. Other anticipated benefits of the study treatment include improving the quality of life of. lt will also lead to the introduction of new processes, materials and methods. lt is also possible to expect shortening of the hospital stay, decrease in postoperative morbidity, and the possibility to perform the procedure on an outpatient basis. The study has been designed as a prospective study, which is in conformity with the principles and guidelines of the Helsinki Declaration, good clinical practice and has been approved by the Ethical Committee of the Faculty of Medicine, University of Ostrava. The patients enrolled in the study are followed for the period of twelve months. Timetable of the study procedures and controls: Preoperative examination: Demographic data on age, sex, weight, height, smoking Assessment of body composition and sampling of blood Questionnaires for quality of Life Examination 3 months postoperatively Assessment of body composition and sampling of blood Questionnaires for quality of Life Examination 6 months after surgery Assessment of body composition and sampling of blood Questionnaires for quality of Life Examination 12 months after surgery Assessment of body composition and sampling of blood Questionnaires for quality of Life Statistical data processing for statistical evaluation descriptive statistics are used (arithmetical average, standard deflection, frequency tables), X2 test, Fisher's exact test, analysis of variance (ANOVA), calculating of the OR (odds ratio) with 95 % confidence intervals, and logistic regression. Statistical tests are evaluated at the significance level of 5%. Statistical analysis is performed in the Stata 10 programme. Program EpiData is used for data collection.

Official Title
-----------------
Metabolic Changes of Fat and Bone Tissue After Radical Bariatric Surgery

Conditions
-----------------
Grade III Obesity, Type 2 Diabetes Mellitus

Intervention / Treatment
-----------------
* Procedure: Laparoscopic sleeve gastrectomy
* Procedure: Laparoscopic gastric plication
* Procedure: Intragastric balloon
* Device: Intragastric balloon implantation


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: History of conservative obesity treatments selected according to criteria IFSO (BMI greater than 40 or greater than 35 with comorbidities) Exclusion Criteria: Thyroid disease Diseases of the digestive system associated with disorders of intestinal absorption History of corticosteroid therapy in the past 12 months

Ages Eligible for Study
-----------------
Minimum Age: 20 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: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Laparoscopic sleeve gastrectomy<br>Patients undergoing bariatric surgery procedure of laparoscopic sleeve gastrectomy. | Procedure: Laparoscopic sleeve gastrectomy<br>* Sleeve gastrectomy involves removing most of the stomach, limiting the amount of food the patient can eat.<br>|
| Active Comparator: Laparoscopic gastric plication<br>Patients undergoing bariatric surgery procedure of laparoscopic gastric plication. | Procedure: Laparoscopic gastric plication<br>* Laparoscopic gastric plication involves sewing one or more large folds in the stomach. During the laparoscopic gastric plication, the stomach volume is reduced about 70%, which makes the stomach able to hold less and helps the patient eat less.<br>|
| Active Comparator: Intragastric balloon<br>Patients undergoing bariatric surgery procedure with intragastric balloon implantation. | Procedure: Intragastric balloon<br>* The introduction of the balloon is non-invasive as it is inserted endoscopically (down the oesophagus). The balloon is then filled inside the stomach with a dyed physiological solution, which reduces the volume of the stomach.<br>Device: Intragastric balloon implantation<br>* Intragastric balloons (End-Ball, Medsil) will be implanted in the patients with morbid obesity.<br>|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in serum levels of adipose tissue hormones | To analyze the dynamics of changes in serum levels of adipose tissue hormones (Leptin, Adiponectin) in adults after bariatric treatment of malignant obesity (BMI> 35). Points of measurements: before the planned intervention and then in intervals of 3, 6, 12, and 18 months after procedure. | 18 months | 
| Changes in serum levels of lipids | To analyze the dynamics of changes in serum levels of lipids in adults after bariatric treatment of malignant obesity (BMI> 35). In the study, serum concentrations of the following lipids will be measured: tricylglycerols, total cholesterol, high-density lipoprotein, low-density lipoprotein cholesterol, Apo D and Apo E. The measurements will be performed before the planned intervention and then in intervals at 3, 6, 12, and 18 months after the procedure. The results will be presented in respective units (mmol/L, mg/dL, etc.). | 18 months | 
| Changes in serum levels of osteomarkers | To analyze the dynamics of changes in serum levels of usual panel of osteomarkers in adults after bariatric treatment of malignant obesity (BMI> 35). The following serum levels markers of bone resorption and formation will be assessed: CTx, P1NP, ALP, RANKL, FGF 23, Osteocalcin, Osteopontin and vitamin D2 and D3. The measurements will be performed before the planned intervention and then in intervals at 3, 6, 12, and 18 months after the procedure. The results will be presented in respective units (mmol/L, mg/dL, etc.). | 18 months | 
| IWQOL Questionnaire evaluation | Evaluation of effects of different types of bariatric interventions on quality of life will be performed by using the IWQOL questionnaire. Improvement from baseline quality of life as measured by standardized IWQOL patient questionnaire (http://www.qualityoflifeconsulting.com/iwqol-lite.html) intended to measure the patient health status. | 18 months | 
| SF-36 Questionnaire evaluation | Evaluation of effects of different types of bariatric interventions on quality of life will be performed using the SF-36 questionnaire. Improvement from baseline quality of life as measured by standardized SF-36 patient questionnaire intended to measure the patient health status. | 18 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Long-term weight reduction assessment in kgs | Evaluation of the success of treatment in terms of long-term weight reduction (difference in body weight in kilograms at the beginning vs. the end of the observation period of 18 months), expressed as TBL (total body weight loss), EWL (excess weight loss), and EBL (excess BMI loss). | 18 months | 
| Effectiveness evaluation | Evaluation of the effectiveness of the specified bariatric procedures, including new intragastric balloons. The following parameters will be assessed at 3, 6, and 12 months: 1) Per cent total body weight loss and excess weight loss at 12 months, 2) Changes in fasting glycaemia, insulin and hemoglobin A1C at 12 months; 3) Reduction in diabetes medication requirements (for diabetic cohort) at 12 months, and 4) Occurrence rate of serious adverse events judged to be probably or definitely related to the study device. | 18 months | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Obesity, Bariatric medicine, Sleeve gastric resection, Gastric plication, Intragastric ballon, Body composition, Adipokines, Ghrelin, Bone mineral density, Quality of life