WildtypeNCT00277342
Potential Association of a Common L-FABP Polymorphism With Lipid-induced Hepatic Insulin Resistance
A study testing measurement of lipid-induced hepatic insulin resistance in people with Wildtype and Polymorphism Liver FABP, run by German Institute of Human Nutrition at 1 site in Germany.
Trial summary
The investigators hypothesise that a common A277G polymorphism of the liver fatty acid binding protein (L-FABP) gene, which leads to an amino acid exchange, may be associated with alterations of lipid-induced hepatic insulin resistance. Read more about this study
- Who is it for?
- Ages 18 to 70 yearsHealthy volunteers can take part
- Conditions the study is for
- Wildtype, Polymorphism Liver FABP
- What is being tested?
- measurement of lipid-induced hepatic insulin resistance
- Type of treatment
- Surgery or procedure
- How many people
- 18 participants
- Where
- 1 siteGermany
- Study dates
- Jan 2006to Apr 2006
- 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 18 to 70 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- healthy subjects with normal glucose tolerance (NGT)
Who cannot join
- any severe cardiac, liver, or kidney diseases
- pregnant or lactating women, menstrual irregularities
- cortisone, antidiabetic drugs
Trial locations and contacts
1 site in 1 country.
Germany1 site
German Institute of Human Nutrition DIfE, Dpt. of Clinical Nutrition, Potsdam-Rehbrücke
Nuthetal, 14558
About this study
The investigators hypothesise that a common A277G polymorphism of the liver fatty acid binding protein (L-FABP) gene, which leads to an amino acid exchange, may be associated with alterations of lipid-induced hepatic insulin resistance. In the present study the investigators will investigate potential differences in lipid-induced hepatic insulin resistance, and in the relation between glycogenolysis and gluconeogenesis, in healthy subjects with the A277G polymorphism vs. subjects carrying the wildtype.
Read the detailed description
Liver fatty acid binding protein (L-FABP) is an abundant cytosolic lipid-binding protein that regulates lipid transport and metabolism. Only one common non-synonymous polymorphism (A227G) leading to an amino-acid exchange in the exonic region of the L-FABP gene has been previously identified. Experimental elevations of free fatty acids (FFAs) have been shown to impair insulin mediated suppression of endogenous glucose production (EGP). Deletion of the L-FABP gene shows no obvious phenotype in mice receiving a low fat chow diet, but leads to decreased hepatic triglyceride accumulation in the prolonged fasted state, which exposes mice to an increased fatty acid flux to the liver. The function of the L-FABP gene may be altered by polymorphisms in coding regions of the gene, probably leading to modifications in hepatic triglyceride accumulation and hepatic insulin resistance.We hypothesize that carriers of the A277G SNP, when compared to matched wild-type subjects, may show altered responses of hepatic glucose production upon exposure to increased peripheral fatty acid concentrations, as achieved by lipid / heparin infusions. Because it is known that free fatty acids potently increase insulin secretion, we use somatostatin clamps in our experiments, followed by replacement of postabsorptive insulin and glucagon concentrations.
- Conditions
- Wildtype, Polymorphism Liver FABP
- Being tested
- measurement of lipid-induced hepatic insulin resistance
- Keywords
- lipid induced hepatic insulin resistance, polymorphisms liver fatty-acid-binding-protein, gluconeogenesis, glycogenolysis, endogenous glucose production
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
measurement of lipid-induced hepatic insulin resistanceProcedure or surgery
What is being measured
The primary outcome is the main question the study is designed to answer.
lipid-induced hepatic insulin resistance(WT vs.SNP L-FABP)
changes in the relation GNG to GL
Secondary outcomes (1)
changes in peripheral plasma glucose and lipid responses
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Jan 2006 (estimated)
- Study startJan 2006
- Study completionApr 2006
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 WildtypeStudies 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 N/A
- Primary purpose
- Diagnosis
- Allocation
- Randomised
- Intervention model
- Single group
- Masking
- Single blind
- Enrolment
- 18 participants
Sponsor and investigators
- Lead sponsor
- German Institute of Human Nutrition
- Sponsor type
- University, hospital or other
- Investigators
- Martin O Weickert, MD, Principal investigator, German Institute of Human Nutrition; Charité Campus Benjamin FranklinMatthias Möhlig, MD, Principal investigator, German Institute of Human Nutrition; Charité Campus Benjamin FranklinAndreas FH Pfeiffer, MD, Study chair, German Institute of Human Nutrition; Charité Campus Benjamin Franklin
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00277342
- Sponsor's protocol ID
- MOW_MM_LFABP
- Status last verified
- Aug 2006
- First submitted
- 12 Jan 2006
- Last updated
- 4 May 2012
- Results posted
- No
Publications
Weickert MO, Loeffelholz CV, Roden M, Chandramouli V, Brehm A, Nowotny P, Osterhoff MA, Isken F, Spranger J, Landau BR, Pfeiffer AF, Mohlig M. A Thr94Ala mutation in human liver fatty acid-binding protein contributes to reduced hepatic glycogenolysis and blunted elevation of plasma glucose levels in lipid-exposed subjects. Am J Physiol Endocrinol Metab. 2007 Oct;293(4):E1078-84. doi: 10.1152/ajpendo.00337.2007. Epub 2007 Aug 14.
PubMed 17698986
Study at a glance
From the registry record, last updated by the sponsor on 4 May 2012. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Potential Association of a Common L-FABP Polymorphism With Lipid-induced Hepatic Insulin Resistance
- ClinicalTrials.gov ID
- NCT00277342
- Acronym / sponsor ID
- MOW_MM_LFABP
- Conditions
- Wildtype, Polymorphism Liver FABP
- Keywords
- lipid induced hepatic insulin resistance, polymorphisms liver fatty-acid-binding-protein, gluconeogenesis, glycogenolysis, endogenous glucose production
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 18 participants
- Lead sponsor
- German Institute of Human NutritionUniversity, hospital or other
- Study start
- Jan 2006
- Study completion
- Apr 2006
- First posted
- 16 Jan 2006 (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.
The investigators hypothesise that a common A277G polymorphism of the liver fatty acid binding protein (L-FABP) gene, which leads to an amino acid exchange, may be associated with alterations of lipid-induced hepatic insulin resistance. In the present study the investigators will investigate potential differences in lipid-induced hepatic insulin resistance, and in the relation between glycogenolysis and gluconeogenesis, in healthy subjects with the A277G polymorphism vs. subjects carrying the wildtype.
Detailed description
Liver fatty acid binding protein (L-FABP) is an abundant cytosolic lipid-binding protein that regulates lipid transport and metabolism. Only one common non-synonymous polymorphism (A227G) leading to an amino-acid exchange in the exonic region of the L-FABP gene has been previously identified. Experimental elevations of free fatty acids (FFAs) have been shown to impair insulin mediated suppression of endogenous glucose production (EGP). Deletion of the L-FABP gene shows no obvious phenotype in mice receiving a low fat chow diet, but leads to decreased hepatic triglyceride accumulation in the prolonged fasted state, which exposes mice to an increased fatty acid flux to the liver. The function of the L-FABP gene may be altered by polymorphisms in coding regions of the gene, probably leading to modifications in hepatic triglyceride accumulation and hepatic insulin resistance.We hypothesize that carriers of the A277G SNP, when compared to matched wild-type subjects, may show altered responses of hepatic glucose production upon exposure to increased peripheral fatty acid concentrations, as achieved by lipid / heparin infusions. Because it is known that free fatty acids potently increase insulin secretion, we use somatostatin clamps in our experiments, followed by replacement of postabsorptive insulin and glucagon concentrations.
Study design
- Primary purpose
- Diagnosis
- Allocation
- Randomised
- Intervention model
- Single group
- Masking
- Single blind
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (1 listed)
- healthy subjects with normal glucose tolerance (NGT)
Key exclusion criteria (3 listed)
- any severe cardiac, liver, or kidney diseases
- pregnant or lactating women, menstrual irregularities
- cortisone, antidiabetic drugs
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 |
|---|---|---|
| measurement of lipid-induced hepatic insulin resistance | Procedure or surgery | – |
Primary outcome
lipid-induced hepatic insulin resistance(WT vs.SNP L-FABP)
changes in the relation GNG to GL
1 secondary outcome
changes in peripheral plasma glucose and lipid responses
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 4 May 2012.
- Results publication: PubMed 17698986Weickert MO, Loeffelholz CV, Roden M, Chandramouli V, Brehm A, Nowotny P, Osterhoff MA, Isken F, Spranger J, Landau BR, Pfeiffer AF, Mohlig M. A Thr94Ala mutation in human liver fatty acid-binding protein contributes to reduced hepatic glycogenolysis and blunted elevation of plasma glucose levels in lipid-exposed subjects. Am J Physiol Endocrinol Metab. 2007 Oct;293(4):E1078-84. doi: 10.1152/ajpendo.00337.2007. Epub 2007 Aug 14.
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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.
Martin O Weickert, MD principal investigator
German Institute of Human Nutrition; Charité Campus Benjamin Franklin
Matthias Möhlig, MD principal investigator
German Institute of Human Nutrition; Charité Campus Benjamin Franklin
Andreas FH Pfeiffer, MD study chair
German Institute of Human Nutrition; Charité Campus Benjamin Franklin
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing measurement of lipid-induced hepatic insulin resistance in people with Wildtype and Polymorphism Liver FABP, run by German Institute of Human Nutrition at 1 site in Germany.
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 1 inclusion and 3 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 4 May 2012. 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 Germany. 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?
lipid-induced hepatic insulin resistance(WT vs.SNP L-FABP). 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 NCT00277342, 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 4 May 2012.