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Fat, Inflammation and Insulin Resistance (FIRE)

The recruitment status of this study is unknown because the information has not been verified recently.
Verified July 2012 by German Diabetes Center.
Recruitment status was  Active, not recruiting
Sponsor:
Information provided by (Responsible Party):
Bettina Nowotny, German Diabetes Center
ClinicalTrials.gov Identifier:
NCT01054989
First received: January 22, 2010
Last updated: July 12, 2012
Last verified: July 2012
  Purpose

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.


Condition Intervention Phase
Healthy Adults With Normal BMI
Biological: Fat/Inflammation effects
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Open Label
Primary Purpose: Basic Science
Official Title: Fat, Inflammation and Insulin Resistance (FIRE-Study)

Resource links provided by NLM:


Further study details as provided by German Diabetes Center:

Primary Outcome Measures:
  • Effect of intervention on whole body insulin sensitivity [ Time Frame: 6 hours ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Effect of intervention on systemic inflammation [ Time Frame: 1-6 hours ] [ Designated as safety issue: No ]
  • Effect of intervention on cellular immune mechanisms [ Time Frame: 6 hours ] [ Designated as safety issue: No ]

Enrollment: 16
Study Start Date: March 2009
Estimated Study Completion Date: October 2012
Primary Completion Date: September 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Fat intravenously
Intravenous application of fat
Biological: Fat/Inflammation effects
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
Biological: Fat/Inflammation effects
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)
Biological: Fat/Inflammation effects
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
Biological: Fat/Inflammation effects
Fat infusion (Intralipid) over 6 hours Fat orally (Soy bean oil) single dose LPS infusion for 10 minutes Glycerol infusion over 6 hours

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.

  Eligibility

Ages Eligible for Study:   20 Years to 40 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01054989

Sponsors and Collaborators
German Diabetes Center
Investigators
Study Director: Michael Roden, Prof., MD German Diabetes Center
Principal Investigator: Bettina Nowotny, MD German Diabetes Center
  More Information

No publications provided by German Diabetes Center

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Bettina Nowotny, Dr. Bettina Nowotny, M.Sc., German Diabetes Center
ClinicalTrials.gov Identifier: NCT01054989     History of Changes
Other Study ID Numbers: FIRE-01
Study First Received: January 22, 2010
Last Updated: July 12, 2012
Health Authority: Germany: Ethics Commission
Germany: Federal Institute for Drugs and Medical Devices

Keywords provided by German Diabetes Center:
Healthy adults
Insulin sensitivity

Additional relevant MeSH terms:
Inflammation
Insulin Resistance
Glucose Metabolism Disorders
Hyperinsulinism
Metabolic Diseases
Pathologic Processes
Insulin
Hypoglycemic Agents
Pharmacologic Actions
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on November 25, 2014