Clinical trial NCT05874726: Biological Sample Repository for Gastrointestinal Disorders
Official title: Biological Sample Repository for Gastrointestinal Disorders
Study type: OBSERVATIONAL
Overall status: SUSPENDED
Conditions: 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
Keywords: 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
Lead sponsor: Brigham and Women's Hospital
Sponsor class: OTHER
Collaborators: name: Tufts University
name: Boston Children's Hospital
name: Mayo Clinic
First posted: 2023-05-25
Enrollment: 500
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_CONTROL
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: The purpose of this repository is to study obesity, as well as the effects of weight loss therapies on several clinical, physiological, hormonal and biochemical parameters. Therefore, enrollment in this repository will be limited to patients with obesity undergoing evaluation for weight loss through medical, endoscopic or surgical means. Obesity is a condition that affects all ethnic and racial groups. Investigators do not anticipate that any particular group of patients will be disproportionately represented. Although obesity affects both children and adults, this repository will be limited to adult patients, which represent the practices of the physicians involved in this protocol.

Brief summary: 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: 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).

Eligibility criteria: 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.

Primary outcomes:
measure: Serum sample repository
timeFrame: Change from Baseline to 10 years.
measure: Urine sample repository
timeFrame: Change from Baseline to 10 years.
measure: Tissue sample repository
timeFrame: Change from Baseline to 10 years.
Secondary outcomes:
Other outcomes:
Locations:
city: Boston
country: United States
facility: Brigham and Women's Hospital
state: Massachusetts
Study officials:
affiliation: Brigham and Women's Hospital
name: Pichamol Jirapinyo, MD, MPH
role: PRINCIPAL_INVESTIGATOR
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