Treatment of Type 2 Diabetes Mellitus by Duodenal Exclusion Associated With Omentectomy: Clinical and Hormonal Study

NCT00566215 | Terminated Phase 1

• 1 other identifier: LIMED0003
• Study Type: interventional
• Target: 6
• Locations: 1 country
• Sites: 1

Brief Summary

Based in a surgery technique studied in a non-obese diabetic mouse model by Rubino and Marescaux(2004), wich reversed diabetes in those animals, we have performed a previous study in human volunteers with type 2 diabetes and overweight (non-obese). The surgery is a duodenal exclusion in wich the stomach volume is kept intact. We observed improvement of glycemic control and hemoglobin A1c, allied to reduction of medicines: insulin was withdrawn or significantly lowered. Further improvement of diabetes could be achieved by intervention in insulin resistance, another factor of diabetes pathophysiology. As that factor is related to visceral fat, we hypothesize that surgical removal of the major omentum, a great component of central adiposity, could beneficial . This study will evaluate the mechanisms of amelioration of type 2 diabetes mellitus after duodenal exclusion surgery plus total omentectomy, by the method of standardized meal stimulus and insulin tolerance test, in human non-obese volunteers with diabetes type 2 and known insulin secretion capacity. The previously studied volunteers submitted to duodenal exclusion without omentectomy will be the control group.

Conditions

Diabetes Mellitus, Type 2; Insulin Resistance; Obesity

Keywords

diabetes mellitus, type 2; Insulin resistance; Intra-Abdominal Fat; Omentum; duodenal exclusion; bariatric surgery; Glucagon-Like Peptide 1; Gastric Inhibitory Polypeptide; insulin; glucagon; ghrelin; adiponectin; Cytokines

Outcome Measures

Primary Outcomes (1)

• Improvement or reversal of type 2 diabetes mellitus

  7 days, 14 days, 21 days, 1 month, 2 months, 3 months, six months and one year

Secondary Outcomes (6)

• Changes in the secretion pattern of incretins, insulin and glucagon after intervention, as measured by standardized mixed meal tolerance test

  2 months, 6 months and 1 year

• Changes in body weight and fat distribution after intervention

  1 month, 2 months, 3 months, 6 months and 1 year

• Changes in seric free fatty acids and lipoproteins

  one month, 2 months, 3 months, 6 months and 1 year

• Regression of carotid intima-media thickness

  1 month, 3 months, 6 months and 1 year

• Changes in seric levels of adiponectin and other adipokines.

  2 months, 6 months and 1 year

Study Arms (2)

1

EXPERIMENTAL

Duodenal exclusion plus total omentectomy

Procedure: Duodenal exclusion plus omentectomy

2

ACTIVE COMPARATOR

Duodenal exclusion without omentectomy

Procedure: Duodenal exclusion without omentectomy

Interventions

Duodenal exclusion plus omentectomy PROCEDURE

Under open laparotomy, a duodenum section 2cm below the pylorus and a jejunum section below Treitz's Angle to create a excluded biliopancreatic limb of 150cm. A Roux-in-Y retrocolic anastomosis of the alimentary limb promotes the gastrojejunal continuity and the anastomosis of the excluded biliopancreatic limb is done 100cm below the jejunal-pyloric union. Additionally, total omentectomy is performed.

Also known as: Duodenojejunal exclusion plus omentectomy, Duodenal-jejunal bypass plus omentectomy

1

Duodenal exclusion without omentectomy PROCEDURE

Under open laparotomy, a duodenum section 2cm below the pylorus and a jejunum section below Treitz's Angle to create a excluded biliopancreatic limb of 150cm. A Roux-in-Y retrocolic anastomosis of the alimentary limb promotes the gastrojejunal continuity and the anastomosis of the excluded biliopancreatic limb is done 100cm below the jejunal-pyloric union.

Also known as: Duodenojejunal exclusion, Duodenal-jejunal bypass

2

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Age: 18 to 60 years.
• BMI between 25 and 29,9 kg/m².
• Weight variance less than 5% in the last 3 months.
• Previous diagnosis of diabetes type 2.
• Insulin requirement, alone or along with oral agents
• Capacity to understand the procedures of the study.
• To agree voluntarily to participate of the study, signing an informed consent.

You may not qualify if:

• Positive Anti-GAD antibodies
• Laboratorial signal of probable failure of insulin production, i. e., seric peptide C lesser than 1 ng/mL.
• History of hepatic disease like cirrhosis or chronic active hepatitis.
• Kidney dysfunction (creatinine \> 1,4 mg/dl in women and \> 1,5 mg/dl in men).
• Hepatic dysfunction: ALT and/or AST 3x above upper normal limit.
• Recent history of neoplasia (\< 5 years).
• Use of oral or injectable corticosteroids for more than consecutive 14 days in the last three months.

Sponsors & Collaborators

• University of Campinas, Brazil: lead

Study Sites (1)

LIMED (Laboratory of Investigation of Metabolism and Diabetes)/GASTROCENTRO/Univeristy of Campinas (UNICAMP)

Campinas, São Paulo, Brazil

Location

Related Publications (6)

• Rubino F, Marescaux J. Effect of duodenal-jejunal exclusion in a non-obese animal model of type 2 diabetes: a new perspective for an old disease. Ann Surg. 2004 Jan;239(1):1-11. doi: 10.1097/01.sla.0000102989.54824.fc.

  PMID: 14685093 BACKGROUND

• Thorne A, Lonnqvist F, Apelman J, Hellers G, Arner P. A pilot study of long-term effects of a novel obesity treatment: omentectomy in connection with adjustable gastric banding. Int J Obes Relat Metab Disord. 2002 Feb;26(2):193-9. doi: 10.1038/sj.ijo.0801871.

  PMID: 11850750 BACKGROUND

• Pitombo C, Araujo EP, De Souza CT, Pareja JC, Geloneze B, Velloso LA. Amelioration of diet-induced diabetes mellitus by removal of visceral fat. J Endocrinol. 2006 Dec;191(3):699-706. doi: 10.1677/joe.1.07069.

  PMID: 17170226 BACKGROUND

• Barzilai N, She L, Liu BQ, Vuguin P, Cohen P, Wang J, Rossetti L. Surgical removal of visceral fat reverses hepatic insulin resistance. Diabetes. 1999 Jan;48(1):94-8. doi: 10.2337/diabetes.48.1.94.

  PMID: 9892227 BACKGROUND

• Gabriely I, Ma XH, Yang XM, Atzmon G, Rajala MW, Berg AH, Scherer P, Rossetti L, Barzilai N. Removal of visceral fat prevents insulin resistance and glucose intolerance of aging: an adipokine-mediated process? Diabetes. 2002 Oct;51(10):2951-8. doi: 10.2337/diabetes.51.10.2951.

  PMID: 12351432 BACKGROUND

• Geloneze B, Geloneze SR, Fiori C, Stabe C, Tambascia MA, Chaim EA, Astiarraga BD, Pareja JC. Surgery for nonobese type 2 diabetic patients: an interventional study with duodenal-jejunal exclusion. Obes Surg. 2009 Aug;19(8):1077-83. doi: 10.1007/s11695-009-9844-4. Epub 2009 May 12.

  PMID: 19475464 RESULT

MeSH Terms

Conditions

Diabetes Mellitus, Type 2; Insulin Resistance; Obesity

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Hyperinsulinism; Overweight; Overnutrition; Nutrition Disorders; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Study Officials

• José Carlos Pareja, MD, PhD

  University of Campinas (UNICAMP)

  PRINCIPAL INVESTIGATOR

• Bruno Geloneze, MD, PhD

  University of Campinas (UNICAMP)

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: November 30, 2007
• First Posted: December 3, 2007
• Study Start: July 1, 2007
• Primary Completion: June 1, 2009
• Study Completion: June 1, 2009
• Last Updated: July 23, 2010

Record last verified: 2010-07

Locations

BR (1)