Small Bowel Diversion

Official title

Jejuno-Ileal and Jejuno-Colic Diversion as a New Bariatric Method in the Treatment of Diabetes and Obesity: Study Protocol for a Prospective Randomised Clinical Trial

Overview

In an effort to replicate metabolic surgery's durable results in metabolic disease while minimizing its risks, two innovative methods has been created. Two surgical methods to create a bowel-to-bowel anastomosis, similar to the type used in current metabolic surgeries. It be to create a jejuno-ileal, side-to-side anastomosis and jejunocolic side-to-side anastomosis. The side-to-side jejuno-ileal anastomosis and side-to-side jejunocolic anastomosis provides two routes for ingested food. The new, shorter route has a malabsorptive effect similar to that seen in Roux en-Y gastric bypass (RYGB) and biliopancreatic diversion (BPD) - procedures which leads to weight loss. Additionally, delivery of non-absorbed macronutrients to the distal ileum, or transverse colon can enhance incretin effect and improve Type 2 Diabetes Mellitus parameters. However, the native route is also preserved, which theoretically reduces the risk of malnutrition, diarrhea, and metabolic derangements seen in other metabolic surgeries.The side-to-side jejuno-ileal anastomosis was already tested in the Pilot Study of the GI Windows Self-Forming Magnetic (SFM) Anastomosis Device for Creation of an Incisionless Small Bowel Bypass for Treatment of Obesity and Diabetes in year 2015 (15). The results of this study demonstrated the safety of this approach without serious adverse events. This non-surgical approach resulted in significant weight loss, favorable changes in insulin and incretin responses to a mixed meal and significant improvement in HbA1c in T2DM (16).In summary, metabolic diseases are a growing pandemic with suboptimal clinical solutions. The surgical side-to-side jejuno-ileal anastomosis and side-to-side jejuno-colic anastomosis without gastrectomy potentially represents a new class of therapy that may produce durable clinical results generally associated with surgery while minimizing its attendant risks.

Detailed description

The study subjects who meet Inclusion criteria and baseline procedures undergo surgery (jejunal-ileal diversion/ jejuno-colic diversion). The surgery is performed in general anesthesia with orotracheal intubation. The laparoscopic approach is used. After establishing pneumoperitoneum (insufluation of the abdominal cavity with CO2) the 1th. trocar and laparoscopic camera are introduced through small incision. After visual control of abdominal cavity additional 2-3 trocars for operating instruments are introduced. The site of future anastomosis is identified (45 cm from ligament of Treitz on jejunum and 45 cm for the ileocoecal junction on ileum). The anastomosis between these two parts of jejunum and ileum is created by the means of linear stapler (45 mm), The residual defect is closed by manual continuous suture. The food will be passed through intestine partially through whole small intestine and partially through the anastomosis. In the second group of patients is the anastomosis created between jejunum (45 from ligament of Treitz) and transverse colon (behind the liver flexure) by means of the same technique. Before the end of the operation the control of bleeding is performed. Afterwards the trocars are removed under visual control. The pneumoperitoneum is released and the incisions are sutured. The subject will have follow-up clinic visits specific to the study at weeks 1, 2, and 3 and at months 1, 2, 3, 6, 12, 18, 24, 30 and 36 after the original procedure. At each clinic visit, the subject will undergo review of medical history, assessment for adverse events, physical examination (including weight and girth measurements) and blood work (e.g. glycated hemoglobin HbA1c). At specific intervals, principal metabolic studies will be performed, including a mixed meal tolerance test. Upper GI series radiographic studies at baseline and 14days after procedure as well as at the discretion of the principal investigator, will be performed, focusing on the patency of the anastomosis.

Interventions

• Procedure jejuno-ileal diversion
  The surgery is performed in general anesthesia with orotracheal intubation. The laparoscopic approach is used. After establishing pneumoperitoneum (insufluation of the abdominal cavity with CO2) the 1th. trocar and laparoscopic camera are introduced through small incision. After visual control of abdominal cavity additional 2-3 trocars for operating instruments are introduced. The site of future anastomosis is identified (45 cm from ligament of Treitz on jejunum and 45 cm for the ileocoecal junc
• Procedure jejuno-colic diversion
  The surgery is performed in general anesthesia with orotracheal intubation. The laparoscopic approach is used. After establishing pneumoperitoneum (insufluation of the abdominal cavity with CO2) the 1th. trocar and laparoscopic camera are introduced through small incision. After visual control of abdominal cavity additional 2-3 trocars for operating instruments are introduced. The anastomosis is created between jejunum (45 from ligament of Treitz) and transverse colon (behind the liver flexure).

Primary outcome measures

• Total body weight loss [Time frame: 36 months]
• Glycated hemoglobin loss [Time frame: 36 months]
• Diabetes medication loss [Time frame: 36 months]
• Total cholesterol loss [Time frame: 36 months]
• Low density lipoprotein loss [Time frame: 36 months]
• High density lipoprotein loss [Time frame: 36 months]
• Leptin metabolism evaluation [Time frame: 36 months]
• Adiponectin metabolism evaluation [Time frame: 36 months]
• Bile acids metabolism evaluation [Time frame: 36 months]

Secondary outcome measures (2)

• Change from baseline quality of life-Lite [Time frame: 36 months]
• Change from baseline quality of life - Sort Form Survey [Time frame: 36 months]

Eligibility criteria

Inclusion criteria

• age 18-65 years at screening;
• Body mass index ≥30 or ≤50kg/m2;
• If subject has Type 2 Diabetes: fasting plasma glucose greater than 6,1 mmol/l at time of enrollment if not treated with anti-diabetic medication;
• If on no diabetes medications, Hemoglobin A1C between and including 6.5 and 9.0 at time of enrollment.

Exclusion criteria

• Body Mass Index >50 or <30 kg/m2;
• Diagnosis of Type 2 diabetes less than 6 months;
• History of suspected gastrointestinal disease (for example cirrhosis, inflammatory bowel disease);
• History of active malignancy (not in remission) with the exception of squamous or basal cell carcinoma of the skin;
• Ongoing systemic infection;
• Chronic pancreatitis;
• Chronic liver disease of any cause;
• Poorly controlled psychiatric disease (for example ongoing major depression, schizophrenia, borderline personality, suicidality, psychosis);
• Any history of an eating disorder within the past 5 years;
• Pre-existing severe comorbid cardio-respiratory disease (for example congestive heart failure, cardiac arrhythmia, coronary artery disease, chronic obstructive lung disease, pulmonary embolism);
• uncontrolled hypertension (systolic Blood Preassure > 150 mm Hg or diastolic Blood Preassure > 100 mm Hg).

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Single blind

Primary purpose

Treatment

Study locations

Czechia · 2 centers

• University of Ostrava — Ostrava
• University of Ostrava, Faculty of Medicine — Ostrava

Publications

• Walpole SC, Prieto-Merino D, Edwards P, Cleland J, Stevens G, Roberts I. The weight of nations: an estimation of adult human biomass. BMC Public Health. 2012 Jun 18;12:439. doi: 10.1186/1471-2458-12-439. PMID 22709383
• 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. PMID 15479938
• Fried M, Yumuk V, Oppert JM, Scopinaro N, Torres AJ, Weiner R, Yashkov Y, Fruhbeck G; European Association for the Study of Obesity; International Federation for the Surgery of Obesity - European Chapter. Interdisciplinary European Guidelines on metabolic and bariatric surgery. Obes Facts. 2013;6(5):449-68. doi: 10.1159/000355480. Epub 2013 Oct 11. PMID 24135948
• 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 PMID 17715408
• Danaei G, Finucane MM, Lu Y, Singh GM, Cowan MJ, Paciorek CJ, Lin JK, Farzadfar F, Khang YH, Stevens GA, Rao M, Ali MK, Riley LM, Robinson CA, Ezzati M; Global Burden of Metabolic Risk Factors of Chronic Diseases Collaborating Group (Blood Glucose). National, regional, and global trends in fasting plasma glucose and diabetes prevalence since 1980: systematic analysis of health examination surveys PMID 21705069
• Hofso D, Jenssen T, Hager H, Roislien J, Hjelmesaeth J. Fasting plasma glucose in the screening for type 2 diabetes in morbidly obese subjects. Obes Surg. 2010 Mar;20(3):302-7. doi: 10.1007/s11695-009-0022-5. Epub 2009 Dec 1. PMID 19949889
• Honzikova N, Krticka A, Zavodna E, Javorka M, Tonhajzerova I, Javorka K. Spectral peak frequency in low-frequency band in cross spectra of blood pressure and heart rate fluctuations in young type 1 diabetic patients. Physiol Res. 2012;61(4):347-54. doi: 10.33549/physiolres.932300. Epub 2012 Jun 6. PMID 22670692
• Rubino F, Nathan DM, Eckel RH, Schauer PR, Alberti KG, Zimmet PZ, Del Prato S, Ji L, Sadikot SM, Herman WH, Amiel SA, Kaplan LM, Taroncher-Oldenburg G, Cummings DE; Delegates of the 2nd Diabetes Surgery Summit. Metabolic Surgery in the Treatment Algorithm for Type 2 Diabetes: a Joint Statement by International Diabetes Organizations. Obes Surg. 2017 Jan;27(1):2-21. doi: 10.1007/s11695-016-2457-9. PMID 27957699

Identifiers

NCT: NCT06374368 · JID-SURG

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗