Biological Sample Repository for Gastrointestinal Disorders

Obesity Clinical Trial

Official title:

Biological Sample Repository for Gastrointestinal Disorders

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05874726
• Other study ID #: 2022P003060
• Status: Recruiting
• Start date: July 19, 2023
• Est. completion date: April 2029

Study information

• Verified date: August 2023
• Source: Brigham and Women's Hospital
• Contact: Michele B Ryan, MS
• Phone: 6175258266
• Email: mryan[@]bwh.harvard.edu
• Is FDA regulated: No
• Study type: Observational [Patient Registry]

Clinical Trial 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.

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).

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 500
• Est. completion date: April 2029
• Est. primary completion date: July 2028
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Cancer
• Collagen Diseases
• Diabetes Mellitus
• Diabetes Mellitus, Type 2
• Diabetes Type 2
• Digestive System Diseases
• Gastro-Intestinal Disorder
• Gastroesophageal Reflux
• Gastrointestinal Diseases
• GERD
• Hyperlipidemias
• Hypertension
• Intestinal Diseases
• Musculoskeletal Pain
• Musculoskeletal Pain Disorder
• Obesity
• Obesity, Morbid
• Overweight
• Overweight and Obesity
• Overweight or Obesity
• Rheumatic Diseases
• Sleep Apnea
• Somatoform Disorders

Intervention

Diagnostic Test:
• Blood Collection
Blood collection via venipuncture
• Urine Collection
Free catch urine sample collection
• Tissue Sample 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.

Locations

Country	Name	City	State
United States	Brigham and Women's Hospital	Boston	Massachusetts

Sponsors (4)

Lead Sponsor	Collaborator
Pichamol Jirapinyo, MD, MPH	Boston Children's Hospital, Mayo Clinic, Tufts University

Country where clinical trial is conducted

United States, 

References & Publications (15)

Anderson JW, Konz EC, Frederich RC, Wood CL. Long-term weight-loss maintenance: a meta-analysis of US studies. Am J Clin Nutr. 2001 Nov;74(5):579-84. doi: 10.1093/ajcn/74.5.579. — View Citation

Buchwald H, Avidor Y, Braunwald E, Jensen MD, Pories W, Fahrbach K, Schoelles K. Bariatric surgery: a systematic review and meta-analysis. JAMA. 2004 Oct 13;292(14):1724-37. doi: 10.1001/jama.292.14.1724. Erratum In: JAMA. 2005 Apr 13;293(14):1728. — View Citation

Buchwald H, Estok R, Fahrbach K, Banel D, Jensen MD, Pories WJ, Bantle JP, Sledge I. Weight and type 2 diabetes after bariatric surgery: systematic review and meta-analysis. Am J Med. 2009 Mar;122(3):248-256.e5. doi: 10.1016/j.amjmed.2008.09.041. — View Citation

Buchwald H, Oien DM. Metabolic/bariatric surgery Worldwide 2008. Obes Surg. 2009 Dec;19(12):1605-11. doi: 10.1007/s11695-009-0014-5. — View Citation

Dixon JB, Lambert GW. The obesity paradox--a reality that requires explanation and clinical interpretation. Atherosclerosis. 2013 Jan;226(1):47-8. doi: 10.1016/j.atherosclerosis.2012.11.005. Epub 2012 Nov 15. No abstract available. — View Citation

Dolan RD, Schulman AR. Endoscopic Approaches to Obesity Management. Annu Rev Med. 2022 Jan 27;73:423-438. doi: 10.1146/annurev-med-042320-125832. Epub 2021 Sep 23. — View Citation

Finkelstein EA, Trogdon JG, Cohen JW, Dietz W. Annual medical spending attributable to obesity: payer-and service-specific estimates. Health Aff (Millwood). 2009 Sep-Oct;28(5):w822-31. doi: 10.1377/hlthaff.28.5.w822. Epub 2009 Jul 27. — View Citation

Guyenet SJ, Schwartz MW. Clinical review: Regulation of food intake, energy balance, and body fat mass: implications for the pathogenesis and treatment of obesity. J Clin Endocrinol Metab. 2012 Mar;97(3):745-55. doi: 10.1210/jc.2011-2525. Epub 2012 Jan 11. — View Citation

Jirapinyo P, Thompson CC. Primary Bariatric Procedures. Dig Dis Sci. 2022 May;67(5):1674-1687. doi: 10.1007/s10620-022-07393-z. Epub 2022 Mar 29. — View Citation

Ogden CL, Yanovski SZ, Carroll MD, Flegal KM. The epidemiology of obesity. Gastroenterology. 2007 May;132(6):2087-102. doi: 10.1053/j.gastro.2007.03.052. — View Citation

Perdomo CM, Cohen RV, Sumithran P, Clement K, Fruhbeck G. Contemporary medical, device, and surgical therapies for obesity in adults. Lancet. 2023 Apr 1;401(10382):1116-1130. doi: 10.1016/S0140-6736(22)02403-5. Epub 2023 Feb 9. — View Citation

Powell AG, Apovian CM, Aronne LJ. New drug targets for the treatment of obesity. Clin Pharmacol Ther. 2011 Jul;90(1):40-51. doi: 10.1038/clpt.2011.82. Epub 2011 Jun 8. — View Citation

Qureshi H, Saeed N, Jovani M. Updates in Endoscopic Bariatric and Metabolic Therapies. J Clin Med. 2023 Jan 31;12(3):1126. doi: 10.3390/jcm12031126. — View Citation

Sjostrom L, Lindroos AK, Peltonen M, Torgerson J, Bouchard C, Carlsson B, Dahlgren S, Larsson B, Narbro K, Sjostrom CD, Sullivan M, Wedel H; Swedish Obese Subjects Study Scientific Group. Lifestyle, diabetes, and cardiovascular risk factors 10 years after bariatric surgery. N Engl J Med. 2004 Dec 23;351(26):2683-93. doi: 10.1056/NEJMoa035622. — View Citation

Sjostrom L, Narbro K, Sjostrom CD, Karason K, Larsson B, Wedel H, Lystig T, Sullivan M, Bouchard C, Carlsson B, Bengtsson C, Dahlgren S, Gummesson A, Jacobson P, Karlsson J, Lindroos AK, Lonroth H, Naslund I, Olbers T, Stenlof K, Torgerson J, Agren G, Carlsson LM; Swedish Obese Subjects Study. Effects of bariatric surgery on mortality in Swedish obese subjects. N Engl J Med. 2007 Aug 23;357(8):741-52. doi: 10.1056/NEJMoa066254. — View Citation

* Note: There are 15 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.
Primary	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.
Primary	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 -80°C until they are "used up" or for up to 10 years from collection.	Change from Baseline to 10 years.