Diabetes Mellitus, Type 2Phase 1/2NCT00566358
Surgical Treatment of Non-obese Type 2 Diabetic Patients With Duodenal Exclusion
A Phase 1/2 study testing Duodenal exclusion surgery in people with Diabetes Mellitus, Type 2, run by University of Campinas, Brazil at 1 site in Brazil.
Trial summary
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… Read more about this study
- Who is it for?
- Ages 18 to 60 years
- Conditions the study is for
- Diabetes Mellitus, Type 2
- What is being tested?
- Duodenal exclusion surgery
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 18 participants
- Where
- 1 siteBrazil
- Study dates
- Jan 2006to Jun 2009
- Phase
- Phase 1/2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 60 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- 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.
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country.
Brazil1 site
LIMED (Laboratory of Investigation of Metabolism and Diabetes)/GASTROCENTRO/Univeristy of Campinas (UNICAMP)
Campinas, São Paulo
About this study
Official title: Lightening the Hormonal Mechanisms of Surgical Treatment of Type 2 Diabetes Mellitus by Duodenal Exclusion Surgery
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.
Read more
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.
Read the 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.
- Conditions
- Diabetes Mellitus, Type 2
- Being tested
- Duodenal exclusion surgery
- Keywords
- diabetes mellitus, type 2, duodenal exclusion, bariatric surgery, Glucagon-Like Peptide 1, Gastric Inhibitory Polypeptide, insulin, glucagon, ghrelin
- Medical subject headings
- Diabetes Mellitus, Type 2, Insulin Resistance
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Duodenal exclusion surgeryProcedure or surgery
Also called Duodeno-jejunal exclusion, Duodenal-jejunal bypass
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.
| Study group | Role | What they receive |
|---|---|---|
| 1 | Experimental | Duodenal exclusion Receives: Procedure: Duodenal exclusion surgery |
What is being measured
The primary outcome is the main question the study is designed to answer.
Improvement or reversal of type 2 diabetes mellitus
Measured: 7 days, 14 days, 21 days, 1 month, 2 months, 3 months, six months and one year.
Changes in the secretion pattern of incretins, insulin and glucagon after intervention, as measured by standardized mixed meal tolerance test
Measured: 2 months, 6 months and 1 year
Secondary outcomes (3)
Changes in body weight and fat distribution after intervention
Measured: 1 month, 2 months, 3 months, 6 months and 1 year
Changes in seric free fatty acids and lipoproteins
Measured: one month, 2 months, 3 months, 6 months and 1 year
Regression of carotid intima-media thickness
Measured: 1 month, 3 months, 6 months and 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Dec 2007 (estimated)
- Study startJan 2006
- Primary completionJun 2009
- Study completionJun 2009
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Diabetes Mellitus, Type 2Studies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 18 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Campinas, Brazil
- Sponsor type
- University, hospital or other
- Collaborators
- Ethicon Endo-Surgery
- Investigators
- Bruno Geloneze, MD, PhD, Principal investigator, University of Campinas (UNICAMP)José Carlos Pareja, MD, PhD, Principal investigator, University of Campinas (UNICAMP)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00566358
- Sponsor's protocol ID
- LIMED0002
- Status last verified
- Jul 2010
- First submitted
- 30 Nov 2007
- Last updated
- 21 Jul 2010
- Results posted
- No
- Data monitoring committee
- No
Publications
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.
PubMed 14685093Geloneze 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.
PubMed 19475464
Study at a glance
From the registry record, last updated by the sponsor on 21 Jul 2010. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Lightening the Hormonal Mechanisms of Surgical Treatment of Type 2 Diabetes Mellitus by Duodenal Exclusion Surgery
- ClinicalTrials.gov ID
- NCT00566358
- Acronym / sponsor ID
- LIMED0002
- Conditions
- Diabetes Mellitus, Type 2
- Keywords
- diabetes mellitus, type 2, duodenal exclusion, bariatric surgery, Glucagon-Like Peptide 1, Gastric Inhibitory Polypeptide, insulin, glucagon, ghrelin
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 18 participants (actual)
- Lead sponsor
- University of Campinas, BrazilUniversity, hospital or other
- Collaborators
- Ethicon Endo-Surgery
- Study start
- Jan 2006
- Primary completion
- Jun 2009 (actual)
- Study completion
- Jun 2009 (actual)
- First posted
- 3 Dec 2007 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| 1 | Experimental | Procedure: Duodenal exclusion surgeryDuodenal exclusion |
Who may qualify
- Ages
- 18 to 60 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (7 listed)
- 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
Key exclusion criteria (7 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Duodenal exclusion surgeryAlso: Duodeno-jejunal exclusion, Duodenal-jejunal bypassUnder 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. | Procedure or surgery | 1 |
Primary outcome
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.
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
3 secondary outcomes
Changes in body weight and fat distribution after intervention
Time frame: 1 month, 2 months, 3 months, 6 months and 1 year
Changes in seric free fatty acids and lipoproteins
Time frame: one month, 2 months, 3 months, 6 months and 1 year
Regression of carotid intima-media thickness
Time frame: 1 month, 3 months, 6 months and 1 year
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Jul 2010.
- Background: PubMed 14685093Rubino 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.
- Results publication: PubMed 19475464Geloneze 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Bruno Geloneze, MD, PhD principal investigator
University of Campinas (UNICAMP)
José Carlos Pareja, MD, PhD principal investigator
University of Campinas (UNICAMP)
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Duodenal exclusion surgery in people with Diabetes Mellitus, Type 2, run by University of Campinas, Brazil at 1 site in Brazil.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 21 Jul 2010. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Brazil. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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.). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00566358, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Jul 2010.