- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01054989
Fat, Inflammation and Insulin Resistance (FIRE)
Fat, Inflammation and Insulin Resistance (FIRE-Study)
The combination of impaired insulin sensitivity and insulin secretion is thought to be the basis of type 2 diabetes. Increased free fatty acids levels impair insulin action in muscle and liver, but also systemic inflammation processes play a role in the development of insulin resistance.
This study compares the effects of fat and inflammation on insulin sensitivity, systemic inflammation, energy metabolism, vascular system and neural function in healthy humans.
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
A dysregulation of lipid metabolism with increased levels of free fatty acids (FFA) is known represent one key mechanism in the pathophysiology of insulin resistance, which is subsequently known to be the basis of the development of type 2 diabetes. But also inflammatory processes, also known as subclinical inflammation, have been shown to be independently associated with insulin resistance and diabetes development. The aim of this study is to analyse the causal relationship between FFA and inflammation in the induction of insulin resistance in healthy humans.
It is known that the parenteral application of lipids over 4-6 hours results in an increase of FFA and a subsequent induction of a transient insulin resistance in peripheral tissues. Whether oral fat intake has similar effect is still unknown. On the other hand the oral intake of a high fat meal acutely increases intestinal permeability and thereby the levels of bacterial lipopolysaccharide (LPS) in the bloodstream. LPS is known to be a potent stimulator of immune response on a subclinical level accompanied by elevated levels of immune mediators, which in turn impair the insulin receptor signalling pathway leading to insulin resistance. Thus, in this study the effects of fat, both by an oral or parenteral fat load, and by a short-term LPS-infusion simulating the postprandial systemic LPS peak compared to a control infusion (glycerol) on insulin resistance is analysed. Insulin resistance and hepatic glucose production is determined by an hyperinsulinemic euglycemic clamp including glucose tracers. To detect the effects on the immune system on different levels, we measure 1) circulating levels of immune mediators by ELISA and bead-based mulitiplex assays, 2) gene expression of leukocytes, 3) subfractions of circulating leukocytes by FACS and 4) the stimulatory capacity of isolated lymphocytes and monocytes in vitro. Moreover, the effects of fat or inflammation on the function of the autonomic nervous system and the vasculature are studied. A second focus is the impact of the interventions on signal transduction and mitochondrial function in muscle and as well as on the metabolism and inflammation in subcutaneous adipose tissue in muscle and fat biopsies.
Study Type
Enrollment (Actual)
Phase
- Phase 4
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Healthy male and female subjects
- Age 20-40
- BMI 20-25 mg/m2
Exclusion Criteria:
- Hyperlipidemia
- Smoking
- Pregnancy
- Acute infection
- Anaemia
- Taking drugs influencing lipid or glucose metabolism, the immune system or antihypertensive medication
- Malignancies
- Any chronic disease
- Autoimmune or immune compromising diseases including HIV/AIDS
- Allergies against study drugs
- Hepatitis
- Gall bladder diseases
- Renal failure
- Psychiatric diseases or addiction
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Basic Science
- Allocation: Randomized
- Interventional Model: Crossover Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Active Comparator: Fat intravenously
Intravenous application of fat
|
Fat infusion (Intralipid) over 6 hours Fat orally (Soy bean oil) single dose LPS infusion for 10 minutes Glycerol infusion over 6 hours
|
Active Comparator: Fat orally
Oral fat load
|
Fat infusion (Intralipid) over 6 hours Fat orally (Soy bean oil) single dose LPS infusion for 10 minutes Glycerol infusion over 6 hours
|
Active Comparator: LPS intravenously
Lipopolysaccharide (LPS; US Standard Reference endotoxin)
|
Fat infusion (Intralipid) over 6 hours Fat orally (Soy bean oil) single dose LPS infusion for 10 minutes Glycerol infusion over 6 hours
|
Placebo Comparator: Glycerol intravenously
Intrevenous glycerol infusion
|
Fat infusion (Intralipid) over 6 hours Fat orally (Soy bean oil) single dose LPS infusion for 10 minutes Glycerol infusion over 6 hours
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
Effect of intervention on whole body insulin sensitivity
Time Frame: 6 hours
|
6 hours
|
Secondary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
Effect of intervention on systemic inflammation
Time Frame: 1-6 hours
|
1-6 hours
|
Effect of intervention on cellular immune mechanisms
Time Frame: 6 hours
|
6 hours
|
Collaborators and Investigators
Sponsor
Investigators
- Study Director: Michael Roden, Prof., MD, German Diabetes Center
- Principal Investigator: Bettina Nowotny, MD, German Diabetes Center
Publications and helpful links
General Publications
- Ziegler D, Strom A, Strassburger K, Nowotny B, Zahiragic L, Nowotny PJ, Carstensen-Kirberg M, Herder C, Szendroedi J, Roden M. Differential Patterns and Determinants of Cardiac Autonomic Nerve Dysfunction during Endotoxemia and Oral Fat Load in Humans. PLoS One. 2015 Apr 20;10(4):e0124242. doi: 10.1371/journal.pone.0124242. eCollection 2015.
- Nowotny B, Zahiragic L, Krog D, Nowotny PJ, Herder C, Carstensen M, Yoshimura T, Szendroedi J, Phielix E, Schadewaldt P, Schloot NC, Shulman GI, Roden M. Mechanisms underlying the onset of oral lipid-induced skeletal muscle insulin resistance in humans. Diabetes. 2013 Jul;62(7):2240-8. doi: 10.2337/db12-1179. Epub 2013 Mar 1.
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- FIRE-01
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Healthy Adults With Normal BMI
-
LG Life SciencesUnknownNormal, Healthy Adults With Moderate, Severe, or Very Severe Volume Loss of Anteromedial Malar RegionKorea, Republic of
-
Purdue UniversityCompletedInvestigate the Maladaptive Eating Behaviors of Normal Healthy AdultsUnited States
-
LG Life SciencesCompletedNormal, Healthy Adults With Moderate, Severe, or Very Severe Volume Loss of Anteromedial Malar Region Who Have Completed the LG-HACL014 StudyKorea, Republic of
-
Monell Chemical Senses CenterHVMN (funding; holder of primary Department of Defense STTR contract)CompletedFlavor Perception in Normal, Healthy AdultsUnited States
-
Ewha Womans UniversityCompletedHealthy Adults With Subjective Sleep ComplaintsKorea, Republic of
-
Thiel, Alexander, M.D.Canadian Institutes of Health Research (CIHR); University of AlbertaNot yet recruiting
-
Ewha Womans UniversityCompletedHealthy Adults With Subjective Memory ComplaintsKorea, Republic of
-
University Hospital, Clermont-FerrandAppetite Control and Energy Balance Research Group, UNiversity of Leeds,... and other collaboratorsTerminatedNormal Weight Adults | Adults With ObesityFrance
-
Ewha Womans UniversityCompletedHealthy Adults With Subjective Memory ComplaintsKorea, Republic of
-
University of DelawareCompletedHealthy Sedentary Adults With BP <140/90United States
Clinical Trials on Fat/Inflammation effects
-
University of FloridaCompleted
-
Kocaeli UniversityCompleted
-
University of MichiganCompletedKidney Diseases | Inflammation | Covid19 | SARS-CoV InfectionUnited States
-
Beijing Anzhen HospitalRecruitingCoronary Artery DiseaseChina
-
Fondazione Policlinico Universitario Agostino Gemelli...Active, not recruiting
-
Ufuk UniversityCompletedOsteoporosis, Postmenopausal | Osteoporotic FracturesTurkey
-
John Paul II Hospital, KrakowJagiellonian University; National Science Centre, PolandRecruitingCoronary Disease | Abdominal Aortic Aneurysm | Coronary Artery AneurysmPoland
-
University of TriesteRecruitingCardiac Surgery | Inflammation GumItaly
-
Maastricht University Medical CenterCompleted
-
Erasme University HospitalFonds National de la Recherche Scientifique; Fonds Erasme; Fonds pour la chirurgie...CompletedHealthy | Diet ModificationBelgium