Type 2 DiabetesNCT00950209
Acute Effect of Intensive Insulin Infusion on Intestinal Triglyceride-rich-lipoprotein-apoB48 Metabolism in Type 2 Diabetic Patients
A study testing saline infusion, euglycaemic hyperinsulinic clamp and infusion of Endolipide and heparin in people with Type 2 Diabetes, run by Assistance Publique Hopitaux De Marseille at 1 site in France.
Trial summary
Atherosclerotic cardiovascular disease (ASCD) is the first cause of morbidity and mortality at type 2 diabetes. The typical dyslipidemia that is associated with insulin resistance, which includes a postprandial elevation of triglyceride-rich lipoproteins (TRLs) with excess of intestinal… Read more about this study
- Who is it for?
- Ages 30 to 70 years, men only
- Conditions the study is for
- Type 2 Diabetes
- What is being tested?
- saline infusion, euglycaemic hyperinsulinic clamp and infusion of Endolipide and heparin
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 20 participants
- Where
- 1 siteFrance
- Study dates
- Apr 2008to Jul 2011
- Phase
- Interventional
- 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 70 years
- Men only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- type 2 diabetic patients according to the criteria of the American Diabetes Association
- body mass index between 25 and 40 kg/m2
- Subject the therapeutic care of which bases only on the oral anti-diabetics excepted of glitazones and inhibitors of alpha-glucosidases
- Subject without cardiovascular event in the previous 6 months or perturbing disease the lipid balance assessment (dysthyroidism, pituitary disease, adrenal disease)
- No anemia, no coagulation disturb, creatinine clearance > 60 ml/min, fasting triglycerides < 4g/l
Who cannot join
- Hypersensitivity to egg
- Subject with severe disease associated with diabete
Trial locations and contacts
1 site in 1 country.
About this study
Atherosclerotic cardiovascular disease (ASCD) is the first cause of morbidity and mortality at type 2 diabetes. The typical dyslipidemia that is associated with insulin resistance, which includes a postprandial elevation of triglyceride-rich lipoproteins (TRLs) with excess of intestinal triglyceride-rich-lipoprotein-apoB48 (TRL-apoB48), is felt to play an important role in the accelerated ASCD.
The investigators' objectives in this study are to determine whether an acute elevation of plasma insulin, secondarily to plasma insulin infusion, modulates the production and the clearance rates of intestinal TRL-apoB48 in type 2 diabetic patients in the fed state and to determine if this is a direct effect of insulin or an indirect effect due to the decrease of plasma FFA or the decrease of plasma glucose.
Read the detailed description
Background: Atherosclerotic cardiovascular disease (ASCD) is the first cause of morbidity and mortality at type 2 diabetes. The typical dyslipidemia that is associated with insulin resistance, which includes a postprandial elevation of triglyceride-rich lipoproteins (TRLs) with excess of intestinal triglyceride-rich-lipoprotein-apoB48 (TRL-apoB48), is felt to play an important role in the accelerated ASCD. Recently, intestinal TRL-apoB48 overproduction appeared as a newly recognized component of insulin resistance. Despite ample evidence supporting the delayed clearance of intestinal TRL-apoB48, there is only a limited amount of information in the literature regarding the factors modulating the production of intestinal TRL-apoB48 in the setting of insulin resistance and type 2 diabetes mellitus. Several arguments suggest that the intestine is not a "passive" organ with respect to lipoprotein production, but an organ metabolically active, receiving information from intestinal lumen and blood and able to modulate its syntheses and its lipid secretions according to the substrata, to the insulin or to other substances. There are functional relationships between the intestine and the liver. For example, it has been recently shown that acute elevation of plasma free fatty acids (FFA) in humans stimulates intestinal TRL-apoB48 and hepatic TRL-apoB100 production.
Aims: Our objectives in this study are to determine whether an acute elevation of plasma insulin, secondarily to plasma insulin infusion, modulates the production and the clearance rates of intestinal TRL-apoB48 in type 2 diabetic patients in the fed state and to determine if this is a direct effect of insuline or an indirect effect due to the decrease of plasma FFA or the decrease of plasma glucose.
Patients and methods: This study will be performed in 30 men with type 2 diabetes in a 2-step protocol. We use a stable isotope method (D3-L-leucine) to study the kinetic of the intestinal TRL-apoB48 and hepatic TRL-apoB100 (production and clearance rates).
In the first step of the protocol, all the patients will have a kinetic study of the TRL-apoB48 in conditions of a saline infusion to measure the "basal" production and clearance rates of the TRL-apoB48. In the second step, type 2 diabetic patients will be divided in 3 different paired groups: one performing an euglycaemic hyperinsulinic clamp to maintain plasma glucose around 1g/l ; one performing an euglycaemic hyperinsulinic clamp to maintain plasma glucose around 1g/l, but being infused with Endolipide 20 % (12,5 ml/h) and heparin (250 U/h) to prevent the suppressive effect of insulin on plasma FFA ; one performing a hyperglycaemic hyperinsulinic clamp to maintain plasma glucose around 2 g/l to prevent the decreasing effect of insulin on plasma glucose.
The research ethics board of the Université de la Méditerranée (Comité de protection des personnes-Sud méditerranée I) and the Afssaps (Agence française de sécurité sanitaire des produits de santé) approved the study and all subjects gave written informed consent prior to their participation.
General objective: Given the potential atherogenicity of the intestinal TRL-apoB48 particles, understanding the factors and the biochemical mechanisms of their accumulation in the plasma in the insulin resistant states may lead to specific therapeutic modalities that reduce their plasma concentration and protect against the highly prevalent atherosclerosis that is associated with insulin resistance and type 2 diabetes.
- Conditions
- Type 2 Diabetes
- Being tested
- saline infusion, euglycaemic hyperinsulinic clamp, infusion of Endolipide and heparin, hyperglycaemic hyperinsulinic clamp
- Keywords
- type 2 diabetic patients in the fed state
- Medical subject headings
- Diabetes Mellitus, Type 2
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
saline infusionDietary supplement
In the first step of the protocol, all the patients will have a kinetic study of the TRL-apoB48 in conditions of a saline infusion to measure the "basal" production and clearance rates of the TRL-apoB48
euglycaemic hyperinsulinic clampOther
an euglycaemic hyperinsulinic clamp to maintain plasma glucose around 1g/l
infusion of Endolipide and heparinDietary supplement
an infusion with Endolipide 20 % (12,5 ml/h) and heparin (250 U/h) to prevent the suppressive effect of insulin on plasma free fatty acids
hyperglycaemic hyperinsulinic clampOther
a hyperglycaemic hyperinsulinic clamp to maintain plasma glucose around 2 g/l to prevent the decreasing effect of insulin on plasma glucose.
| Study group | Role | What they receive |
|---|---|---|
| euglycaemic hyperinsulinic clamp | Active comparator | In the first step of the protocol, all the patients will have a kinetic study of the TRL-apoB48 in conditions of a saline infusion to measure the "basal" production and clearance rates of the TRL-apoB48. In the second step,the patients of this arm will perform an euglycaemic hyperinsulinic clamp to maintain plasma glucose around 1g/l. Receives: Dietary Supplement: saline infusion; Other: euglycaemic hyperinsulinic clamp |
| euglycaemic hyperinsulinic clamp with Endolipide and heparin | Active comparator | In the first step of the protocol, all the patients will have a kinetic study of the TRL-apoB48 in conditions of a saline infusion to measure the "basal" production and clearance rates of the TRL-apoB48. In the second step,the patients of this arm will perform an euglycaemic hyperinsulinic clamp to maintain plasma glucose around 1g/l but will be also infused with Endolipide 20 % (12,5 ml/h) and heparin (250 U/h) to prevent the suppressive effect of insulin on plasma free fatty acids. Receives: Dietary Supplement: saline infusion; Other: euglycaemic hyperinsulinic clamp; Dietary Supplement: infusion of Endolipide and heparin |
| hyperglycaemic hyperinsulinic clamp | Active comparator | In the first step of the protocol, all the patients will have a kinetic study of the TRL-apoB48 in conditions of a saline infusion to measure the "basal" production and clearance rates of the TRL-apoB48. In the second step,the patients of this arm will perform a hyperglycaemic hyperinsulinic clamp to maintain plasma glucose around 2 g/l to prevent the decreasing effect of insulin on plasma glucose. Receives: Dietary Supplement: saline infusion; Other: hyperglycaemic hyperinsulinic clamp |
What is being measured
The primary outcome is the main question the study is designed to answer.
To determine whether an acute elevation of plasma insulin, secondarily to plasma insulin infusion, modulates the production and the clearance rates of intestinal TRL-apoB48 in type 2 diabetic patients in the fed state
Measured: 3 years
Secondary outcomes (1)
To determine if this is a direct effect of insulin or an indirect effect due to the decrease of plasma FFA or the decrease of plasma glucose.
Measured: 3 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted31 Jul 2009 (estimated)
- Study startApr 2008
- Primary completionJul 2011
- Study completionJul 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 Type 2 DiabetesStudies of the same condition, open and under way.
- More trials run by Assistance Publique Hopitaux De MarseilleThe sponsor's other registered studies.
- 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 N/A
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 20 participants (actual)
Sponsor and investigators
- Lead sponsor
- Assistance Publique Hopitaux De Marseille
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Rene Valero, Principal investigator, Assistance Publique Hopitaux De Marseille
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00950209
- Sponsor's protocol ID
- 2007/17
- Other IDs
- 2007-002791-33
- Status last verified
- Feb 2014
- First submitted
- 30 Jul 2009
- Last updated
- 25 Feb 2014
- Results posted
- No
- Data monitoring committee
- No
Publications
Nogueira JP, Maraninchi M, Beliard S, Padilla N, Duvillard L, Mancini J, Nicolay A, Xiao C, Vialettes B, Lewis GF, Valero R. Absence of acute inhibitory effect of insulin on chylomicron production in type 2 diabetes. Arterioscler Thromb Vasc Biol. 2012 Apr;32(4):1039-44. doi: 10.1161/ATVBAHA.111.242073. Epub 2012 Feb 2.
PubMed 22308041
Study at a glance
From the registry record, last updated by the sponsor on 25 Feb 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Acute Effect of Intensive Insulin Infusion on Intestinal Triglyceride-rich-lipoprotein-apoB48 Metabolism in Type 2 Diabetic Patients
- ClinicalTrials.gov ID
- NCT00950209
- Acronym / sponsor ID
- 2007/17
- Conditions
- Type 2 Diabetes
- Keywords
- type 2 diabetic patients in the fed state
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 20 participants (actual)
- Lead sponsor
- Assistance Publique Hopitaux De MarseilleUniversity, hospital or other
- Study start
- Apr 2008
- Primary completion
- Jul 2011 (actual)
- Study completion
- Jul 2011 (actual)
- First posted
- 31 Jul 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.
Atherosclerotic cardiovascular disease (ASCD) is the first cause of morbidity and mortality at type 2 diabetes. The typical dyslipidemia that is associated with insulin resistance, which includes a postprandial elevation of triglyceride-rich lipoproteins (TRLs) with excess of intestinal triglyceride-rich-lipoprotein-apoB48 (TRL-apoB48), is felt to play an important role in the accelerated ASCD.
The investigators' objectives in this study are to determine whether an acute elevation of plasma insulin, secondarily to plasma insulin infusion, modulates the production and the clearance rates of intestinal TRL-apoB48 in type 2 diabetic patients in the fed state and to determine if this is a direct effect of insulin or an indirect effect due to the decrease of plasma FFA or the decrease of plasma glucose.
Detailed description
Background: Atherosclerotic cardiovascular disease (ASCD) is the first cause of morbidity and mortality at type 2 diabetes. The typical dyslipidemia that is associated with insulin resistance, which includes a postprandial elevation of triglyceride-rich lipoproteins (TRLs) with excess of intestinal triglyceride-rich-lipoprotein-apoB48 (TRL-apoB48), is felt to play an important role in the accelerated ASCD. Recently, intestinal TRL-apoB48 overproduction appeared as a newly recognized component of insulin resistance. Despite ample evidence supporting the delayed clearance of intestinal TRL-apoB48, there is only a limited amount of information in the literature regarding the factors modulating the production of intestinal TRL-apoB48 in the setting of insulin resistance and type 2 diabetes mellitus. Several arguments suggest that the intestine is not a "passive" organ with respect to lipoprotein production, but an organ metabolically active, receiving information from intestinal lumen and blood and able to modulate its syntheses and its lipid secretions according to the substrata, to the insulin or to other substances. There are functional relationships between the intestine and the liver. For example, it has been recently shown that acute elevation of plasma free fatty acids (FFA) in humans stimulates intestinal TRL-apoB48 and hepatic TRL-apoB100 production.
Aims: Our objectives in this study are to determine whether an acute elevation of plasma insulin, secondarily to plasma insulin infusion, modulates the production and the clearance rates of intestinal TRL-apoB48 in type 2 diabetic patients in the fed state and to determine if this is a direct effect of insuline or an indirect effect due to the decrease of plasma FFA or the decrease of plasma glucose.
Patients and methods: This study will be performed in 30 men with type 2 diabetes in a 2-step protocol. We use a stable isotope method (D3-L-leucine) to study the kinetic of the intestinal TRL-apoB48 and hepatic TRL-apoB100 (production and clearance rates).
In the first step of the protocol, all the patients will have a kinetic study of the TRL-apoB48 in conditions of a saline infusion to measure the "basal" production and clearance rates of the TRL-apoB48. In the second step, type 2 diabetic patients will be divided in 3 different paired groups: one performing an euglycaemic hyperinsulinic clamp to maintain plasma glucose around 1g/l ; one performing an euglycaemic hyperinsulinic clamp to maintain plasma glucose around 1g/l, but being infused with Endolipide 20 % (12,5 ml/h) and heparin (250 U/h) to prevent the suppressive effect of insulin on plasma FFA ; one performing a hyperglycaemic hyperinsulinic clamp to maintain plasma glucose around 2 g/l to prevent the decreasing effect of insulin on plasma glucose.
The research ethics board of the Université de la Méditerranée (Comité de protection des personnes-Sud méditerranée I) and the Afssaps (Agence française de sécurité sanitaire des produits de santé) approved the study and all subjects gave written informed consent prior to their participation.
General objective: Given the potential atherogenicity of the intestinal TRL-apoB48 particles, understanding the factors and the biochemical mechanisms of their accumulation in the plasma in the insulin resistant states may lead to specific therapeutic modalities that reduce their plasma concentration and protect against the highly prevalent atherosclerosis that is associated with insulin resistance and type 2 diabetes.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| euglycaemic hyperinsulinic clamp | Active comparator | Dietary Supplement: saline infusion, Other: euglycaemic hyperinsulinic clampIn the first step of the protocol, all the patients will have a kinetic study of the TRL-apoB48 in conditions of a saline infusion to measure the "basal" production and clearance rates of the TRL-apoB48. In the second step,the patients of this arm will perform an euglycaemic hyperinsulinic clamp to maintain plasma glucose around 1g/l. |
| euglycaemic hyperinsulinic clamp with Endolipide and heparin | Active comparator | Dietary Supplement: saline infusion, Other: euglycaemic hyperinsulinic clamp, Dietary Supplement: infusion of Endolipide and heparinIn the first step of the protocol, all the patients will have a kinetic study of the TRL-apoB48 in conditions of a saline infusion to measure the "basal" production and clearance rates of the TRL-apoB48. In the second step,the patients of this arm will perform an euglycaemic hyperinsulinic clamp to maintain plasma glucose around 1g/l but will be also infused with Endolipide 20 % (12,5 ml/h) and heparin (250 U/h) to prevent the suppressive effect of insulin on plasma free fatty acids. |
| hyperglycaemic hyperinsulinic clamp | Active comparator | Dietary Supplement: saline infusion, Other: hyperglycaemic hyperinsulinic clampIn the first step of the protocol, all the patients will have a kinetic study of the TRL-apoB48 in conditions of a saline infusion to measure the "basal" production and clearance rates of the TRL-apoB48. In the second step,the patients of this arm will perform a hyperglycaemic hyperinsulinic clamp to maintain plasma glucose around 2 g/l to prevent the decreasing effect of insulin on plasma glucose. |
Who may qualify
- Ages
- 30 to 70 years
- Sex
- Male only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- type 2 diabetic patients according to the criteria of the American Diabetes Association
- body mass index between 25 and 40 kg/m2
- Subject the therapeutic care of which bases only on the oral anti-diabetics excepted of glitazones and inhibitors of alpha-glucosidases
- Subject without cardiovascular event in the previous 6 months or perturbing disease the lipid balance assessment (dysthyroidism, pituitary disease, adrenal disease)
- No anemia, no coagulation disturb, creatinine clearance > 60 ml/min, fasting triglycerides < 4g/l
Key exclusion criteria (2 listed)
- Hypersensitivity to egg
- Subject with severe disease associated with diabete
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 |
|---|---|---|
| saline infusionIn the first step of the protocol, all the patients will have a kinetic study of the TRL-apoB48 in conditions of a saline infusion to measure the "basal" production and clearance rates of the TRL-apoB48 | Dietary supplement | euglycaemic hyperinsulinic clamp, euglycaemic hyperinsulinic clamp with Endolipide and heparin, hyperglycaemic hyperinsulinic clamp |
| euglycaemic hyperinsulinic clampan euglycaemic hyperinsulinic clamp to maintain plasma glucose around 1g/l | Other | euglycaemic hyperinsulinic clamp, euglycaemic hyperinsulinic clamp with Endolipide and heparin |
| infusion of Endolipide and heparinan infusion with Endolipide 20 % (12,5 ml/h) and heparin (250 U/h) to prevent the suppressive effect of insulin on plasma free fatty acids | Dietary supplement | euglycaemic hyperinsulinic clamp with Endolipide and heparin |
| hyperglycaemic hyperinsulinic clampa hyperglycaemic hyperinsulinic clamp to maintain plasma glucose around 2 g/l to prevent the decreasing effect of insulin on plasma glucose. | Other | hyperglycaemic hyperinsulinic clamp |
Primary outcome
To determine whether an acute elevation of plasma insulin, secondarily to plasma insulin infusion, modulates the production and the clearance rates of intestinal TRL-apoB48 in type 2 diabetic patients in the fed state
Time frame: 3 years
1 secondary outcome
To determine if this is a direct effect of insulin or an indirect effect due to the decrease of plasma FFA or the decrease of plasma glucose.
Time frame: 3 years
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 25 Feb 2014.
- Derived from this study: PubMed 22308041Nogueira JP, Maraninchi M, Beliard S, Padilla N, Duvillard L, Mancini J, Nicolay A, Xiao C, Vialettes B, Lewis GF, Valero R. Absence of acute inhibitory effect of insulin on chylomicron production in type 2 diabetes. Arterioscler Thromb Vasc Biol. 2012 Apr;32(4):1039-44. doi: 10.1161/ATVBAHA.111.242073. Epub 2012 Feb 2.
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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.
Rene Valero principal investigator
Assistance Publique Hopitaux De Marseille
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing saline infusion, euglycaemic hyperinsulinic clamp and infusion of Endolipide and heparin in people with Type 2 Diabetes, run by Assistance Publique Hopitaux De Marseille at 1 site in France.
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 5 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 25 Feb 2014. 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 France. 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?
To determine whether an acute elevation of plasma insulin, secondarily to plasma insulin infusion, modulates the production and the clearance rates of intestinal TRL-apoB48 in type 2 diabetic patients in the fed state (time frame: 3 years). 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 NCT00950209, 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 25 Feb 2014; AzTrials last refreshed its copy on 7 Nov 2026.