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

This study has been terminated.
(Benefit of duodenal exclusion alone less than expected for treatment of type 2 diabetes; an additional effect of combination with omentectomy not observed)
Sponsor:
Information provided by:
University of Campinas, Brazil
ClinicalTrials.gov Identifier:
NCT00566215
First received: November 30, 2007
Last updated: July 22, 2010
Last verified: July 2010
  Purpose

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 We observed improvement of glycemic control and hemoglobin A1c, allied to reduction of medicines: insulin was withdrawn or significantly lowered.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.


Condition Intervention Phase
Diabetes Mellitus, Type 2
Insulin Resistance
Obesity
Procedure: Duodenal exclusion plus omentectomy
Procedure: Duodenal exclusion without omentectomy
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Clinical and Hormonal Study of a New Surgical Treatment of Type 2 Diabetes Mellitus: Duodenal Exclusion Associated With Omentectomy

Resource links provided by NLM:


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 ]

Secondary Outcome Measures:
  • 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 ]
  • 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 ]
  • Changes in seric levels of adiponectin and other adipokines. [ Time Frame: 2 months, 6 months and 1 year ] [ Designated as safety issue: No ]
  • Improvement of insulin sensitivity as measured by insulin tolerance test. [ Time Frame: 1 month, 3 months, 6 months and 1 year ] [ Designated as safety issue: No ]

Enrollment: 6
Study Start Date: July 2007
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 plus total omentectomy
Procedure: Duodenal exclusion plus omentectomy

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.

Other Names:
  • Duodenojejunal exclusion plus omentectomy
  • Duodenal-jejunal bypass plus omentectomy
Active Comparator: 2
Duodenal exclusion without omentectomy
Procedure: Duodenal exclusion without omentectomy
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.
Other Names:
  • Duodenojejunal exclusion
  • Duodenal-jejunal bypass

Detailed Description:

Diabetes reversion is observed after bariatric surgeries even before significant weight loss could explain it, mainly in predominantly malabsorptive procedures, followed by those combining malabsorption and gastric restriction. Changes in the hormonal communication between the digestive system (incretins)and the pancreas would explain the antidiabetogenic role of the surgery, so this effect could be obtained in nonobese, diabetic individuals.

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: the stomach volume is kept intact, maintaining the caloric ingestion and the weight reduces less than 5%, without the potential nutritional deprivations commonly seen in the bariatric surgery. We observed improvement of glycemic control and hemoglobin A1c, allied to reduction of medicines: insulin was withdrawn or significantly lowered. An standardized mixed meal tolerance test showed favorable changes in the gastrointestinal hormones that stimulate insulin secretion (incretins): increase of GLP-1 and reduction of GIP.

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 .

In fact, surgical removal of visceral fat in rodents improves insulin sensitivity. A pilot study in human, obese volunteers submitted to gastric adjustable band was promising int this aspect.

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.

  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
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Please refer to this study by its ClinicalTrials.gov identifier: NCT00566215

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

Publications:
Responsible Party: Bruno Geloneze, University of Campinas, Brazil
ClinicalTrials.gov Identifier: NCT00566215     History of Changes
Other Study ID Numbers: LIMED0003
Study First Received: November 30, 2007
Last Updated: July 22, 2010
Health Authority: Brazil: National Committee of Ethics in Research

Keywords provided by University of Campinas, Brazil:
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

Additional relevant MeSH terms:
Diabetes Mellitus
Diabetes Mellitus, Type 2
Insulin Resistance
Endocrine System Diseases
Glucose Metabolism Disorders
Hyperinsulinism
Metabolic Diseases

ClinicalTrials.gov processed this record on October 20, 2014