Biological Sample Repository for Gastrointestinal Disorders

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).

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.