Surgical Treatment of Non-obese Type 2 Diabetic Patients With Duodenal Exclusion - Full Text View

Sponsor:	University of Campinas, Brazil
Collaborator:	Ethicon Endo-Surgery
Information provided by:	University of Campinas, Brazil
ClinicalTrials.gov Identifier:	NCT00566358

Purpose

Diabetes reversion is observed after bariatric surgeries even before significant weight loss could explain it, mainly in predominantly malabsorptive procedures (98,9% for biliopancreatic diversion or duodenal switch), followed by those combining malabsorption and gastric restriction (83,7% for Roux-en-Y gastric bypass). Changes in the hormonal communication between the digestive system and the pancreas would explain the antidiabetogenic role of the surgery, so this effect could be obtained in nonobese, diabetic individuals.

In order to try this hypothesis, RUBINO and MARESCAUX (2004) studied the gastrojejunal bypass (duodenal exclusion)in an mouse model of diabetes without obesity. In their technique the stomach volume is kept intact, maintaining the caloric ingestion and the weight of the animals. There was a fast improvement of diabetes, independent of diet and weight, without the potential nutritional deprivations commonly seen in the bariatric surgery like iron and vitamin deficiency.

This study will evaluate the mechanisms of amelioration of type 2 diabetes mellitus after duodenal exclusion surgery in human non-obese, diabetic volunteers and known insulin secretion capacity, by the method of standardized meal stimulus. It is expected to be secondary to changes in the gastrointestinal hormones that stimulate insulin secretion (incretins).

The knowledge about the clinical outcomes of this technique in humans and the description of the secretion pattern of gastrointestinal hormones after the surgery may contribute to the implementation of this surgery as a new therapeutic option for overweight (non-obese) diabetic patients.

Condition	Intervention	Phase
Diabetes Mellitus, Type 2	Procedure: Duodenal exclusion surgery	Phase I Phase II

Study Type:	Interventional
Study Design:	Endpoint Classification: Safety/Efficacy Study Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	Lightening the Hormonal Mechanisms of Surgical Treatment of Type 2 Diabetes Mellitus by Duodenal Exclusion Surgery

Resource links provided by NLM:

Genetics Home Reference related topics: 6q24-related transient neonatal diabetes mellitus

MedlinePlus related topics: Diabetes Diabetes Medicines Diabetes Type 2 Weight Loss Surgery

U.S. FDA Resources

Further study details as provided by University of Campinas, Brazil:

Primary Outcome Measures:

Improvement or reversal of type 2 diabetes mellitus [ Time Frame: 7 days, 14 days, 21 days, 1 month, 2 months, 3 months, six months and one year. ] [ Designated as safety issue: No ]
Changes in the secretion pattern of incretins, insulin and glucagon after intervention, as measured by standardized mixed meal tolerance test [ Time Frame: 2 months, 6 months and 1 year ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Changes in body weight and fat distribution after intervention [ Time Frame: 1 month, 2 months, 3 months, 6 months and 1 year ] [ Designated as safety issue: No ]
Changes in seric free fatty acids and lipoproteins [ Time Frame: one month, 2 months, 3 months, 6 months and 1 year ] [ Designated as safety issue: No ]
Regression of carotid intima-media thickness [ Time Frame: 1 month, 3 months, 6 months and 1 year ] [ Designated as safety issue: No ]

Enrollment:	18
Study Start Date:	January 2006
Study Completion Date:	June 2009
Primary Completion Date:	June 2009 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: 1 Duodenal exclusion	Procedure: Duodenal exclusion surgery Under open laparotomy, a duodenum section 2cm below the pylorus and a jejunum section below Treitz's Angle to create an 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. Other Names: Duodeno-jejunal exclusion Duodenal-jejunal bypass

Arms

Assigned Interventions

Experimental: 1

Duodenal exclusion

Procedure: Duodenal exclusion surgery

Under open laparotomy, a duodenum section 2cm below the pylorus and a jejunum section below Treitz's Angle to create an 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.

Other Names:

Duodeno-jejunal exclusion
Duodenal-jejunal bypass

Detailed Description:

There is large recovery of insulin sensibility after bariatric surgery, as the patients get closer to ideal weight. Diabetes reversion is more frequent after predominantly malabsorptive procedures (98,9% for biliopancreatic diversion or duodenal switch), followed by those combining malabsorption and gastric restriction (83,7% for Roux-en-Y gastric bypass). Glycemia normalization occurs in an early phase of the postoperative period, even before significant weight loss could explain it. These techniques have in common a bypass of the duodenum and part of the jejunum. Many peptides are released in this segments that regulate pancreatic beta cells (insulin producers) either in physiological state or in diabetes. Anatomical-functional changes in the enteroinsular axis would explain the antidiabetogenic role of the surgery, so this effect could be obtained in nonobese, diabetic individuals.

In order to try this hypothesis, RUBINO and MARESCAUX (2004) studied the gastrojejunal bypass (duodenal exclusion)in Goto-Kakizaki mice (GK), the most used animal model of diabetes without obesity. In their technique the stomach volume is kept intact, maintaining the caloric ingestion and the weight of the animals. There was a fast improvement of diabetes, independent of diet and weight. The authors concluded that this procedure should be applied in humans for reversal of diabetes without the potential nutritional deprivations commonly seen in the bariatric surgery like iron and vitamin deficiency.

The amelioration of diabetes after bariatric surgery is related to the modulation of production of gastrointestinal hormones relevant to the insulin production (incretin effect).

This study will evaluate the mechanisms of amelioration of type 2 diabetes mellitus after duodenal exclusion surgery in human non-obese, diabetic volunteers and known insulin secretion capacity, by the method of standardized meal stimulus. It is expected to be secondary to changes in the gastrointestinal hormones that stimulate insulin secretion (incretins).

The knowledge about the clinical outcomes of this technique in humans and the description of the secretion pattern of gastrointestinal hormones after the surgery may contribute to the implementation of this surgery as a new therapeutic option for overweight (non-obese) diabetic patients.

Eligibility

Ages Eligible for Study:	18 Years to 60 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

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.

Exclusion Criteria:

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.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00566358

Locations

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

Sponsors and Collaborators

University of Campinas, Brazil

Ethicon Endo-Surgery

Investigators

Principal Investigator:	Bruno Geloneze, MD, PhD	University of Campinas (UNICAMP)
Principal Investigator:	José Carlos Pareja, MD, PhD	University of Campinas (UNICAMP)

More Information

Publications:

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. Epub 2009 May 12.

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.

Responsible Party:	Bruno Geloneze, University of Campinas, Brazil
ClinicalTrials.gov Identifier:	NCT00566358 History of Changes
Other Study ID Numbers:	LIMED0002
Study First Received:	November 30, 2007
Last Updated:	July 20, 2010
Health Authority:	Brazil: National Committee of Ethics in Research

Keywords provided by University of Campinas, Brazil:

diabetes mellitus, type 2
duodenal exclusion
bariatric surgery
Glucagon-Like Peptide 1

Gastric Inhibitory Polypeptide
insulin
glucagon
ghrelin

Additional relevant MeSH terms:

Diabetes Mellitus
Diabetes Mellitus, Type 2
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Gastric Inhibitory Polypeptide
Incretins

Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Pharmacologic Actions
Gastrointestinal Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on February 12, 2012