ObesityNCT00994435
The Incretin Secretion in the Gut System Related to the Physiological Stimulus
An observational study of Obesity, run by Catholic University of the Sacred Heart at 1 site in Italy.
Trial summary
Insulin secretion and insulin sensitivity are related with an inverse, hyperbolic function, the so called disposition index, that shows the critical importance of the ß-cell dysfunction for the development of T2DM. Read more about this study
- Who is it for?
- Ages 30 to 60 years
- Conditions the study is for
- Obesity
- How many people
- 20 participants
- Where
- 1 siteItaly
- Study dates
- Jan 2009to Jan 2011
- Phase
- Observational
- 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 30 to 60 years
- All sexes
- No healthy volunteers
- Adult
Study population: Studies are carried out in 20 obese subjects of both gender sexes, 10 of whom with type 2 diabetics and 10 with normal glucose tolerance.
Who may be able to join
- Males and females
- Women in fertile age should engage themselves in avoiding pregnancy during the study protocol. Before starting each experimental session a pregnancy test will be performed and pregnant women excluded from the investigation. All women will be studied in the follicular phase of their menstrual cycle 30 to 60 years old.
- HbA1c between 6.5 and 8.5% (for patients with T2DM only)
- BMI between 30-40 Kg /m2
Who cannot join
- Past or active medical history of major endocrinological, renal, cardiac, respiratory, liver or gastro-intestinal diseases.
- All Diabetic patients must have never been treated with oral hypoglycemic agents or insulin.
Trial locations and contacts
1 site in 1 country.
Italy1 site
Department of Metabolic Diseases, Institute of Internal Medicine - Catholic University
Rome, Rome, 00168
About this study
Insulin secretion and insulin sensitivity are related with an inverse, hyperbolic function, the so called disposition index, that shows the critical importance of the ß-cell dysfunction for the development of T2DM. A consequence of the hyperbolic relationship is that increased insulin resistance is compensated by up-regulation of insulin secretion, as it happens in obesity. However, when a defective insulin secretion in relation to insulin sensitivity takes place (i.e. reduced disposition index) then impaired glucose tolerance or type 2 diabetes develop. The investigators have recently demonstrated that bilio-pancreatic diversion determines a prompt reversibility of T2DM by normalizing peripheral insulin sensitivity and enhancing ß-cell sensitivity to glucose; these changes occur within few days after surgery, largely before changes in body weight occur. This operation may affect the entero-insular axis function, by diverting nutrients away from the proximal gastro-intestinal tract and by delivering incompletely digested nutrients to the ileum, thus abnormally stimulating the secretion of intestinal incretins. It has been shown that male Wistar rats undergoing three different types of small intestinal surgery, namely ileal transposition (either 10 or 20 cm of lower ileum transposed to mid-duodenum) or 85% jejuno-ileal bypass, showed a sustained post-operative reduction in food intake and a significant change in body weight gain. All experimental groups had a large increase in basal and meal-stimulated enteroglucagon, while the area under the curve of plasma levels of gastrin, gastric inhibitory polypeptide (GIP), insulin and blood glucose were significantly reduced. GIP is produced mainly in the duodenum and jejunum as shown in dogs .The aim of the present study is to investigate the intestinal site of production of incretins in response to intraluminal nutrients stimulation in order to establish the relationship between insulin resistance, insulin hypersecretion and different small intestinal segments in insulin resistance conditions, such as obesity and T2DM. To this purpose a mixed test meal will be infused in the duodenum, proximal jejunum or ileum and glucose uptake and insulin secretion studied, in relation to glucagon and incretin response. Studies are carried out in 20 obese subjects of both sexes, 10 of whom with type 2 diabetes and 10 with normal glucose tolerance.
Read the detailed description
For intestinal perfusion, a tube assembly (outer diameter 7 mm) marked with a length scale is used. It consists of six tubes that are bonded together with tetrahydrofuran (Sigma Chemical Corp, St Louis, Missouri, USA). Three tubes are connected to a balloon which is used to occlude the intestinal lumen proximal to the site of infusion. Three tubes are radio-opaque to allow fluoroscopic location of the assembly; their distal end is immediately distal to the proximal occluding balloon(perfusion site) and positioned at 60 cm (duodenum), 90 cm (proximal jejunum) and 120 cm (distal jejunum) from the nose. After a 12 hour fast, the subjects swallow the tube assembly. The position of the assembly is confirmed by fluoroscopy. With the tube in the right position, the occluding balloon is inflated with 60 ml of air and perfusion of the distal intestinal segment is started. . The perfusion is performed using a continuous pump according to the following scheme:
100 ml/h during 30 minutes 110 ml/h during 60 minutes 123 ml/h during 60 minutes 133 ml/h during 30 minutes test period, which is followed by 120 minute absorption period. Each subject will be studied in 3 different sessions at 7-10 days distance randomly selected in order to study the effect on insulin sensitivity and secretion of a test meal delivery in different intestinal segments (i.e. at the duodenum, the proximal jejunum, and the distal jejunum). Blood samples for glucose, free fatty acids (FFA) insulin, C-peptide, glucagon, GLP-1, GIP, are drawn at -30 minutes and at 0, 15, 30, 40, 60, 80, 100, 120, 150, 180, 240, 300 and 360 minutes during each of the test periods. The lipid-glucose-protein test meal is a mixture of ScandiShake(85 g of powder is mixed in 240-mL milk resulting in 69.5 g carbohydrates, 30.4 g fat, and 11.7 g protein).
- Conditions
- Obesity
- Keywords
- obesity
- Medical subject headings
- Obesity
What is being measured
The primary outcome is the main question the study is designed to answer.
dosage for glucose, free fatty acids (FFA) insulin, C-peptide, glucagon, GLP-1, GIP
Measured: 3 test meals of 360 minutes duration each, taken at a time distance of 7-10 days . Overall duration, approximally 30 days for each patient.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Oct 2009 (estimated)
- Study startJan 2009
- Primary completionJul 2010
- Study completionJan 2011
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for ObesityStudies 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
- Observational
- Observational model
- Case only
- Time perspective
- Prospective
- Enrolment
- 20 participants (actual)
Sponsor and investigators
- Lead sponsor
- Catholic University of the Sacred Heart
- Sponsor type
- University, hospital or other
- Investigators
- Giovanni Ghirlanda, MD, Principal investigator, Catholic University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00994435
- Sponsor's protocol ID
- 1082/08
- Status last verified
- Oct 2009
- First submitted
- 1 Oct 2009
- Last updated
- 24 Mar 2011
- Results posted
- No
- Data monitoring committee
- No
Publications
Salinari S, Carr RD, Guidone C, Bertuzzi A, Cercone S, Riccioni ME, Manto A, Ghirlanda G, Mingrone G. Nutrient infusion bypassing duodenum-jejunum improves insulin sensitivity in glucose-tolerant and diabetic obese subjects. Am J Physiol Endocrinol Metab. 2013 Jul 1;305(1):E59-66. doi: 10.1152/ajpendo.00559.2012. Epub 2013 May 7.
PubMed 23651846
Study at a glance
From the registry record, last updated by the sponsor on 24 Mar 2011. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Incretin Secretion in the Gut System Related to the Physiological Stimulus
- ClinicalTrials.gov ID
- NCT00994435
- Acronym / sponsor ID
- 1082/08
- Conditions
- Obesity
- Keywords
- obesity
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 20 participants (actual)
- Lead sponsor
- Catholic University of the Sacred HeartUniversity, hospital or other
- Study start
- Jan 2009
- Primary completion
- Jul 2010 (actual)
- Study completion
- Jan 2011 (actual)
- First posted
- 14 Oct 2009 (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.
Insulin secretion and insulin sensitivity are related with an inverse, hyperbolic function, the so called disposition index, that shows the critical importance of the ß-cell dysfunction for the development of T2DM. A consequence of the hyperbolic relationship is that increased insulin resistance is compensated by up-regulation of insulin secretion, as it happens in obesity. However, when a defective insulin secretion in relation to insulin sensitivity takes place (i.e. reduced disposition index) then impaired glucose tolerance or type 2 diabetes develop. The investigators have recently demonstrated that bilio-pancreatic diversion determines a prompt reversibility of T2DM by normalizing peripheral insulin sensitivity and enhancing ß-cell sensitivity to glucose; these changes occur within few days after surgery, largely before changes in body weight occur. This operation may affect the entero-insular axis function, by diverting nutrients away from the proximal gastro-intestinal tract and by delivering incompletely digested nutrients to the ileum, thus abnormally stimulating the secretion of intestinal incretins. It has been shown that male Wistar rats undergoing three different types of small intestinal surgery, namely ileal transposition (either 10 or 20 cm of lower ileum transposed to mid-duodenum) or 85% jejuno-ileal bypass, showed a sustained post-operative reduction in food intake and a significant change in body weight gain. All experimental groups had a large increase in basal and meal-stimulated enteroglucagon, while the area under the curve of plasma levels of gastrin, gastric inhibitory polypeptide (GIP), insulin and blood glucose were significantly reduced. GIP is produced mainly in the duodenum and jejunum as shown in dogs .The aim of the present study is to investigate the intestinal site of production of incretins in response to intraluminal nutrients stimulation in order to establish the relationship between insulin resistance, insulin hypersecretion and different small intestinal segments in insulin resistance conditions, such as obesity and T2DM. To this purpose a mixed test meal will be infused in the duodenum, proximal jejunum or ileum and glucose uptake and insulin secretion studied, in relation to glucagon and incretin response. Studies are carried out in 20 obese subjects of both sexes, 10 of whom with type 2 diabetes and 10 with normal glucose tolerance.
Detailed description
For intestinal perfusion, a tube assembly (outer diameter 7 mm) marked with a length scale is used. It consists of six tubes that are bonded together with tetrahydrofuran (Sigma Chemical Corp, St Louis, Missouri, USA). Three tubes are connected to a balloon which is used to occlude the intestinal lumen proximal to the site of infusion. Three tubes are radio-opaque to allow fluoroscopic location of the assembly; their distal end is immediately distal to the proximal occluding balloon(perfusion site) and positioned at 60 cm (duodenum), 90 cm (proximal jejunum) and 120 cm (distal jejunum) from the nose. After a 12 hour fast, the subjects swallow the tube assembly. The position of the assembly is confirmed by fluoroscopy. With the tube in the right position, the occluding balloon is inflated with 60 ml of air and perfusion of the distal intestinal segment is started. . The perfusion is performed using a continuous pump according to the following scheme:
100 ml/h during 30 minutes 110 ml/h during 60 minutes 123 ml/h during 60 minutes 133 ml/h during 30 minutes test period, which is followed by 120 minute absorption period. Each subject will be studied in 3 different sessions at 7-10 days distance randomly selected in order to study the effect on insulin sensitivity and secretion of a test meal delivery in different intestinal segments (i.e. at the duodenum, the proximal jejunum, and the distal jejunum). Blood samples for glucose, free fatty acids (FFA) insulin, C-peptide, glucagon, GLP-1, GIP, are drawn at -30 minutes and at 0, 15, 30, 40, 60, 80, 100, 120, 150, 180, 240, 300 and 360 minutes during each of the test periods. The lipid-glucose-protein test meal is a mixture of ScandiShake(85 g of powder is mixed in 240-mL milk resulting in 69.5 g carbohydrates, 30.4 g fat, and 11.7 g protein).
Study design
- Observational model
- Case only
- Time perspective
- Prospective
Who may qualify
- Ages
- 30 to 60 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
- Study population
- Studies are carried out in 20 obese subjects of both gender sexes, 10 of whom with type 2 diabetics and 10 with normal glucose tolerance.
Key inclusion criteria (4 listed)
- Males and females
- Women in fertile age should engage themselves in avoiding pregnancy during the study protocol. Before starting each experimental session a pregnancy test will be performed and pregnant women excluded from the investigation. All women will be studied in the follicular phase of their menstrual cycle 30 to 60 years old.
- HbA1c between 6.5 and 8.5% (for patients with T2DM only)
- BMI between 30-40 Kg /m2
Key exclusion criteria (2 listed)
- Past or active medical history of major endocrinological, renal, cardiac, respiratory, liver or gastro-intestinal diseases.
- All Diabetic patients must have never been treated with oral hypoglycemic agents or insulin.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
dosage for glucose, free fatty acids (FFA) insulin, C-peptide, glucagon, GLP-1, GIP
Time frame: 3 test meals of 360 minutes duration each, taken at a time distance of 7-10 days . Overall duration, approximally 30 days for each patient.
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 24 Mar 2011.
- Derived from this study: PubMed 23651846Salinari S, Carr RD, Guidone C, Bertuzzi A, Cercone S, Riccioni ME, Manto A, Ghirlanda G, Mingrone G. Nutrient infusion bypassing duodenum-jejunum improves insulin sensitivity in glucose-tolerant and diabetic obese subjects. Am J Physiol Endocrinol Metab. 2013 Jul 1;305(1):E59-66. doi: 10.1152/ajpendo.00559.2012. Epub 2013 May 7.
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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.
Giovanni Ghirlanda, MD principal investigator
Catholic University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Obesity, run by Catholic University of the Sacred Heart at 1 site in Italy.
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 4 inclusion and 2 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 24 Mar 2011. 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 Italy. 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.
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?
dosage for glucose, free fatty acids (FFA) insulin, C-peptide, glucagon, GLP-1, GIP (time frame: 3 test meals of 360 minutes duration each, taken at a time distance of 7-10 days . Overall duration, approximally 30 days for each patient.). 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 NCT00994435, which also lists 1 linked publication.
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 24 Mar 2011.