Biological Sample Repository for Gastrointestinal Disorders

Study Overview
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Brief Summary
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The goal of this observational study has the purpose of collecting biological samples from obese patients undergoing evaluation for weight loss by means of medical or endoscopic therapies; and of post bariatric surgery patients presenting with short- and long-term surgical complications. The aim is to enhance the overall understanding of the mechanisms leading to obesity, weight loss, failure to lose weight, and weight regain following treatment. Additional goals are to determine the efficacy of endoscopic and surgical procedures, to identify potential therapeutic targets and disease biomarkers that predict response to therapy.

Detailed Description
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The prevalence of obesity in the U.S. has reached unacceptably high numbers over the past three decades. Approximately 68% of the American population over the age of 20 is overweight, while 35.7% meet criteria for obesity (CDC). Obesity has become a leading cause of morbidity, mortality and reduced quality of life; and places patients at high risk for several chronic conditions, including: diabetes (DM), hypertension (HTN), hyperlipidemia (HL), sleep apnea, GERD, musculoskeletal disorders and cancer. In addition, obesity imposes a major burden in the American healthcare system, with an estimated annual cost of 147 billion U.S. dollars. Treatment of obesity is challenging. Preventive measures and medical therapy have not been effective in fighting this epidemic. Diet and exercise, though logical, are hindered by high recidivism and a propensity to regain weight to pre-weight loss levels. Anti-obesity drugs are largely ineffective and limited by safety and side-effects profile. Even bariatric surgery, which provides significant and rapid weight loss, is still followed by substantial weight regain over time. In addition, surgery is associated with a 1% mortality risk, 5-25% 1-year morbidity, and is not readily accessible. Fewer than 1% of eligible obese patients undergo surgery each year. In face of all these challenges, there is an urgent need to better understand the pathophysiology of obesity and the effects of current weight loss interventions. This knowledge will provide a new framework for the development of more effective preventive measures and therapies. The pathophysiology of obesity is complex. Weight gain results from an energy imbalance; that is, when energy intake is higher than expenditure. In this context, obesity has been attributed to a shift in diet toward increased consumption of energy-dense foods, and to sedentary lifestyle. However, little is known about the physiological mechanisms underlying this trend, which are thought to be regulated by genetic, metabolic and neurobehavioral factors. Even less is understood on how increased adiposity leads to the development of many metabolic disorders, including DM. Surprisingly, these mechanisms can be reversed by bariatric procedures, which in addition to weight loss, have dramatic beneficial effects on metabolic disorders such as DM, HTN, and HL. Therefore, surgery has become an important study tool to enhance our understanding of the pathophysiology of obesity. The collection of biological samples from patients before and after weight loss therapies, including endoscopic and surgical procedures, will provide the basis for a series of studies that will focus on investigating: the mechanisms that lead to obesity, particularly appetite and gut regulatory peptides; the clinical, physiological, hormonal and metabolic changes imposed by medical, surgical and endoscopic procedures to treat obesity; the mechanisms of weight regain following bariatric surgery; the mechanism of failure to lose weight following endoscopic or surgical procedures; the effects of endoscopic procedures on weight regain following bariatric surgery; biomarkers that predict response to medical, endoscopic and surgical therapies; biomarkers that predict weight regain or therapeutic failures; novel therapeutic targets for the treatment of obesity. Medical therapies include weight loss diets or anti-obesity medications. Bariatric endoscopic procedures include ablation techniques, intragastric balloons, submucosal tunneling procedures (PSAM, GEM, G-POEM), tissue plication platforms (POSE, ROSE), endoluminal sleeves and endoscopic suturing devices (ESG). Bariatric surgical procedures include laparoscopic adjustable gastric banding (LAGB), laparoscopic sleeve gastrectomy (LSG), Roux-en-Y gastric bypass (RYGB), bilio-pancreatic diversion (BPD) with or without duodenal switch (BPD-DS).

Official Title
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Biological Sample Repository for Gastrointestinal Disorders

Conditions
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Obesity, Obesity, Morbid, Obesity, Primary, Gastro-Intestinal Disorder, Overweight and Obesity, Overweight, Overweight or Obesity, Diabetes Type 2, Diabetes Mellitus, Diabetes Mellitus, Type 2, Hypertension, Hyperlipidemias, Sleep Apnea, GERD, Gastroesophageal Reflux, Musculoskeletal Pain Disorder, Cancer

Intervention / Treatment
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* Diagnostic Test: Blood Collection
* Diagnostic Test: Urine Collection
* Diagnostic Test: Tissue Sample Collection


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Be older than 18 years of age, Suffer from obesity, defined by BMI≥30 kg/m2 (body mass index: weight in kilograms divided by the square of the height in meters). Exclusion Criteria: Positive laboratory tests for any of the following pathogens: Hepatitis B virus (HBV); Hepatitis C virus (HCV); Human Immunodeficiency Virus Types 1 and 2 (HIV); Human T-Lymphotropic virus Types I and II (HTLV); Treponema pallidum (syphilis); Clostridium Difficile (C. Diff) History of gastrointestinal malabsorptive disorders including a known history of celiac disease, and/or chronic pancreatitis, History of any inflammatory disease of the gastrointestinal tract, Patient is of childbearing age and not practicing effective birth control method, pregnant or lactating History of a myocardial infarction or cerebro-vascular accident in the last year, or history of unstable cardiovascular disease, History of cancer or life expectancy of < 2 yrs, Use of any medications (prescription or OTC), including herbal or other supplements for treatment of obesity, History of known hormonal or genetic cause for obesity, History of any psychiatric disorders including dementia, active psychosis, severe depression requiring > 2 medications, history of suicide attempts, alcohol or drug abuse within the previous 12 months, Any condition or major illness that, in the investigator's judgment, places the subject at undue risk of participating in the repository, Unable to understand the risks, realistic benefits and requirements of the repository, Use of investigational therapy or participation in any other clinical trial within 12 weeks prior to signing the ICF.

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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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Bariatric Surgery Patients<br>Subjects who have had bariatric surgery for obesity - primary and revision. Bariatric surgical procedures include laparoscopic adjustable gastric banding (LAGB), laparoscopic sleeve gastrectomy (LSG), Roux-en-Y gastric bypass (RYGB), bilio-pancreatic diversion (BPD) with or without duodenal switch (BPD-DS). | Diagnostic Test: Blood Collection<br>* Blood collection via venipuncture<br>Diagnostic Test: Urine Collection<br>* Free catch urine sample collection<br>Diagnostic Test: Tissue Sample Collection<br>* Tissue (gastric, duodenum, jejunum and ileum - number of biopsies will be 3-4 from each site, ranging in size from 4-7mm) - These samples collected will be extra biopsies that are taken for research purposes during a clinically planned endoscopy for which biopsies are being planned.<br>* Other names: Biopsy;|
| Endoscopic Metabolic and Bariatric Therapies<br>Subjects who have had endoscopic bariatric therapies for obesity - primary and revision. Bariatric endoscopic procedures include ablation techniques, intragastric balloons, submucosal tunneling procedures (PSAM, GEM, G-POEM), tissue plication platforms (POSE, ROSE), endoluminal sleeves and endoscopic suturing devices (ESG). | Diagnostic Test: Blood Collection<br>* Blood collection via venipuncture<br>Diagnostic Test: Urine Collection<br>* Free catch urine sample collection<br>Diagnostic Test: Tissue Sample Collection<br>* Tissue (gastric, duodenum, jejunum and ileum - number of biopsies will be 3-4 from each site, ranging in size from 4-7mm) - These samples collected will be extra biopsies that are taken for research purposes during a clinically planned endoscopy for which biopsies are being planned.<br>* Other names: Biopsy;|
| Medical Management<br>Subjects who follow lifestyle modification and/or anti-obesity medications for treatment of obesity with no previous surgical intervention for obesity. Medical therapies include weight loss diets or anti-obesity medications. | Diagnostic Test: Blood Collection<br>* Blood collection via venipuncture<br>Diagnostic Test: Urine Collection<br>* Free catch urine sample collection<br>Diagnostic Test: Tissue Sample Collection<br>* Tissue (gastric, duodenum, jejunum and ileum - number of biopsies will be 3-4 from each site, ranging in size from 4-7mm) - These samples collected will be extra biopsies that are taken for research purposes during a clinically planned endoscopy for which biopsies are being planned.<br>* Other names: Biopsy;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Serum sample repository | Blood (10 ml) will be collected from the enrolled subjects, serum will be extracted and stored at -80 degrees for up to 10 years. | Change from Baseline to 10 years. | 
| Urine sample repository | Urine (5 ml) will be collected via free catch method and stored at -80 degrees C for up to 10 years. | Change from Baseline to 10 years. | 
| Tissue sample repository | Tissue samples (gastric, duodenum, jejunum and ileum - number of biopsies will be 3-4 from each site, ranging in size from 4-7mm) will be collected during a scheduled endoscopic examination. Biopsy tissue will be collected with a large capacity biopsy forceps and deposited into a conical vial containing a freshly prepared balanced salt solution including a HEPES buffer at the bedside, using 5mL of buffered salt solution per 5-10 mm3 of tissue biopsy, at 4 degrees C. Tissue will be stored at -80⁰C until they are used up or for up to 10 years from collection. | Change from Baseline to 10 years. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Gut Hormones, Bariatric Surgery, Weight Loss, Weight Loss Diets, Anti-obesity Medications, Endoscopic Metabolic and Bariatric Therapies (EMBT), Bariatric Endoscopy, Intragastric balloon (IGB), Ablation Techniques, Submucosal Tunneling Procedures, pylorus sparing antral myotomy (PSAM), gastroplasty with endoscopic myotomy (GEM), Gastric peroral endoscopic myotomy (G-POEM), Tissue Plication, Primary Obesity Surgery Endolumenal (POSE), Restorative Obesity Surgery Endoluminal (ROSE), Endoluminal sleeves, Endoscopic Suturing, Endoscopic Sleeve Gastroplasty (ESG), laparoscopic adjustable gastric banding (LAGB), laparoscopic sleeve gastrectomy (LSG), Roux-en-Y gastric bypass (RYGB), bilio-pancreatic diversion (BPD), bilio-pancreatic diversion with duodenal switch (BPD-DS), Pathophysiology of obesity