Symptoms and General Pathology

All Conditions

Neoplasms

Digestive System Diseases

Nutritional and Metabolic Diseases

Behaviors and Mental Disorders

Nervous System Diseases

Rare Diseases

Syndrome

Esophageal Neoplasms

Nutrition Disorders

Gastroparesis

Dumping Syndrome

Feeding and Eating Disorders

Gastrointestinal Diseases

Stomach Diseases

Paralysis

Neurologic Manifestations

Postgastrectomy Syndromes

Postoperative Complications

Mental Disorders

Psychotic Disorders

Esophageal Cancer

Hypoglycemic Agents

All Drugs and Chemicals

Pharmaceutical Solutions

Anti-Infective Agents

Anti-Inflammatory Agents

Antirheumatic Agents

Analgesics

Gastrointestinal Agents

Antineoplastic Agents

Antipyretics

Insulin

Insulin, Globin Zinc

Hormones

Somatostatin

Glucagon-Like Peptide 1

Sulfasalazine

Octreotide

Acetaminophen

Analgesics, Non-Narcotic

Antineoplastic Agents, Hormonal

Anti-Inflammatory Agents, Non-Steroidal

50mcg octreotide acetate by subcutaneous injection 10 minutes prior to a 400kcal mixed meal challenge

Octreotide Acetate

Equivalent volume of 0.9% saline by subcutaneous injection 10 minutes prior to a 400kcal mixed meal challenge

Saline Solution

Paracetamol 1g by mouth consumed with a 400kcal mixed meal challenge

Paracetamol

1g sulfasalazine by mouth consumed with a 400kcal mixed meal challenge

Biopsy from the second part of the duodenum taken at routine endoscopic surveillance, undertaken for another clinical indication.

Duodenal biopsy

John V Reynolds, MD FRCS

Carel W le Roux, FRCP FRCPath PhD

The incidence of oesophagogastric cancer has increased by 400% since the 1970s in Ireland and the United Kingdom. In addition, refinement of perioperative management and the now widespread use of multimodal protocols for patients with locally advanced disease have significantly improved outcomes for patients with oesophagogastric cancer treatable with curative intent. Despite significant advances in chemoradiotherapy, surgical resection remains the primary curative option.

Unintentional weight loss and nutritional complications represent serious concerns for patients after radical resection, even among those who remain free from recurrent disease in the long-term. A study from the Swedish Esophageal and Cardia Cancer Registry reported a mean three year weight loss of 10.8% among disease-free patients, with 33.8% of this cohort demonstrating malnutrition at three years post-oesophagectomy.

Mechanisms contributing to weight loss for disease-free patients after upper gastrointestinal surgery are poorly understood, however an association between increasing magnitude of weight loss and the presence of increased satiety is described. Our recent studies at SJH have demonstrated four fold elevated postprandial satiety gut hormone concentrations after oesophagectomy, compared with baseline preoperative values. Postprandial gut hormone levels correlate significantly with postprandial symptoms and altered appetite at 3 months postoperatively, and with body weight loss at 2 years postoperatively. However, the mechanism leading to exaggerated postprandial gut hormone production after upper gastrointestinal surgery is poorly understood, limiting targeted therapeutic options.

In this study, we aim to characterise the role of altered nutrient transit and enteroendocrine cell function in the pathophysiology of excessive post-prandial gut hormone responses after upper gastrointestinal surgery. To do this, we will measure the gut hormone response to a standardised 400 kcal meal, as per previous studies, while concurrently assessing gastrointestinal transit time, and enteroendocrine cell morphology and function. In this way, we will determine whether the magnitude of the postprandial gut hormone response correlates with the rate of nutrient transit into the enteroendocrine L-cell rich small intestine, and whether enteroendocrine cell adaptation occurs after oesophagectomy.

Furthermore, we have previously observed that gut hormone suppression using octreotide is associated with increased ad libitum among subjects after upper gastrointestinal cancer surgery (Elliott JA et al, Annals of Surgery, 2015). The mechanism of action of octreotide may relate to SSTR-5-mediated negative feedback to the enteroendocrine L-cell, but this medication may additionally reduce enteroendocrine L-cell responses through its inhibitory effect on gastrointestinal motility - reducing the rapidity with which nutrients are delivered to the small intestine - and small intestinal nutrient sensing via inhibition of the Na+-dependent glucose transporter SGLT-18-10. Through conduction of this double-blind, randomised, placebo-controlled crossover study, we aim to establish the mechanism of action of octreotide-mediated increased food intake in patients after gastrointestinal surgery. This may inform the design of future targeted interventions for this patient group.

Gastrointestinal Nutrient Transit and Enteroendocrine Function After Upper Gastrointestinal Surgery

St. James's Hospital, Ireland

Clinical Research Fellow

Gland and Hormone Related Diseases

Heart and Blood Diseases

Respiratory Tract (Lung and Bronchial) Diseases

Musculoskeletal Diseases

Skin and Connective Tissue Diseases

Ear, Nose, and Throat Diseases

Diabetes Mellitus

Diabetes Mellitus, Type 2

Overweight

Hyperlipoproteinemias

Hyperlipidemias

Intestinal Diseases

Obesity

Body Weight

Hypertension

Gastroesophageal Reflux

Weight Loss

Apnea

Sleep Apnea Syndromes

Rheumatic Diseases

Collagen Diseases

Pain

Obesity, Morbid

Musculoskeletal Pain

Somatoform Disorders

Metabolic Diseases

Glucose Metabolism Disorders

Endocrine System Diseases

Overnutrition

Esophageal Motility Disorders

Esophageal Spasm, Diffuse

Deglutition Disorders

Esophageal Diseases

Dyslipidemias

Lipid Metabolism Disorders

Muscular Diseases

Connective Tissue Diseases

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).

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).

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.

Blood Collection

Urine Collection

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.

Tissue Sample Collection

Michele B Ryan, MS

Michele B. Ryan, MS

Pichamol Jirapinyo, MD, MPH

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.

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).

* Blood (serum will be extracted and stored at -80⁰C),
* Urine (stored at -80⁰C),
* 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.
* Data from medical records will be collected including: age, gender, vitals, weight, bmi, graphs, medical history, surgical history, endoscopy reports, radiology reports, labs, demographics, medications, problem list. Investigators do plan to continue collecting data into the future.

Biological Sample Repository for Gastrointestinal Disorders

MGB and non-MGB investigators may request samples (any of the samples listed in this protocol) from this tissue repository. This request will be made after establishing a formal collaboration with investigators in this protocol. Requests will be made in the form of a written document stating the title and purpose of the project, as well as which experimental procedures will be done with the repository samples. In addition to a written request, collaborators will have to share their approved IRB protocol with the investigators in this 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.

Urine (5 ml) will be collected via free catch method and stored at -80 degrees C for up to 10 years.

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.

Tufts University

Boston Children's Hospital

Mayo Clinic

Associate Director of Bariatric Endoscopy

Weight Gain

Body Weight Changes

Psychotropic Drugs

Central Nervous System Depressants

Antidepressive Agents

Mirtazapine

This cohort will be the group who are undergoing routine clinical treatment with a long-acting somatostatin analogue to minimise abnormal gut hormone signalling, and thus reduce early satiety.

This cohort will be the group who are undergoing routine clinical treatment with a tetracyclic antidepressant to stimulate appetite.

Patients undergo clinical treatment as indicated, they are studied before and after.

Clinical treatment

The investigators aim to ascertain how food reward signals and eating behaviour relates to the gut-brain pathway in weight-losing patients after curative surgery for oesophageal cancer, and how this pathway responds to clinical treatment for this unintentional weight loss. The primary outcomes are the blood oxygen level dependent (BOLD) signal on functional MRI (fMRI), and the breakpoint during the progressive ratio task (PRT - a measure of eating behaviour), how these differ in response to multiple clinical treatment options, as well as how they relate to weight gain while on treatment.

The incidence of cancer of the oesophagus (food pipe) is increasing. Improvements in treatment strategies have resulted in more people who remain free from cancer recurrence in the long term following treatment.

Surgery is the cornerstone of treatment for patients with oesophageal cancer, but while surgical removal of the tumour (oesophagectomy) may offer the best chance of cure, these are major operations associated with specific long term complications. Poor appetite, weight loss and nutritional impairment are common problems among patients who attain long-term cancer remission and cure after surgery.

A new clinic has been established to treat patients who are in remission but who have lost more than 10% of their body weight secondary to the effects of the surgery and struggling to regain weight. These patients will be treated as per standard of care with medications to aid weight gain.

The investigators are interested to conduct research into how the reward value of food changes during the clinical treatment pathway. The hypothesis is that there will be an increased reward response to food after medication use, the magnitude of which will correlate with weight gain. To assess this, patients who are already part of this clinic will be approached to have fMRI that can demonstrate changes in brain reward centres as well as a Progressive Ratio Task, which is a direct measure of appetitive behaviour. Changes in brain reward centre responses and appetitive behaviour will be correlated with changes in weight after pharmacotherapy. This may further inform future clinical protocols to provide improved precision medicine.

Resection of the Esophagus and Subsequent Weight Loss

The Effect of Clinical Treatment for Unintentional Weight Loss on Food Reward and Appetitive Behaviour in Patients Who Have Lost >10% of Their Body Weight After Undergoing Curative Surgery for Oesophageal Cancer

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Gastrointestinal Nutrient Transit and Enteroendocrine Function After Upper Gastrointestinal Surgery	NCT03734627	Esophageal Canc... Nutrition Disor... Appetite Disord... Dumping Syndrom... Delayed Gastric... Surgery	Octreotide Acet... Saline Solution Paracetamol Sulfasalazine Duodenal biopsy	18 Years -	St. James's Hospital, Ireland
Biological Sample Repository for Gastrointestinal Disorders	NCT05874726	Obesity Obesity, Morbid Obesity, Primar... Gastro-Intestin... Overweight and ... Overweight Overweight or O... Diabetes Type 2 Diabetes Mellit... Diabetes Mellit... Hypertension Hyperlipidemias Sleep Apnea GERD Gastroesophagea... Musculoskeletal... Cancer	Blood Collectio... Urine Collectio... Tissue Sample C...	18 Years -	Brigham and Women's Hospital
Resection of the Esophagus and Subsequent Weight Loss	NCT03377660	Esophageal Canc... Weight Gain Eating Behavior Food Reward	Clinical treatm...	18 Years -	Imperial College London
Biological Sample Repository for Gastrointestinal Disorders	NCT05874726	Obesity Obesity, Morbid Obesity, Primar... Gastro-Intestin... Overweight and ... Overweight Overweight or O... Diabetes Type 2 Diabetes Mellit... Diabetes Mellit... Hypertension Hyperlipidemias Sleep Apnea GERD Gastroesophagea... Musculoskeletal... Cancer	Blood Collectio... Urine Collectio... Tissue Sample C...	18 Years -	Brigham and Women's Hospital

Spots Global Cancer Trial Database for gut hormones

Every month we try and update this database with for gut hormones cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.