Healthy Adults With Normal BMIPhase 4FIRENCT01054989
Fat, Inflammation and Insulin Resistance
A Phase 4 study testing Fat/Inflammation effects in people with Healthy Adults With Normal BMI, run by German Diabetes Center.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 20 to 40 yearsHealthy volunteers can take part
- Conditions the study is for
- Healthy Adults With Normal BMI
- What is being tested?
- Fat/Inflammation effects
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 16 participants
- Where
- No sites listed yet
- Study dates
- 15 Mar 2009to 15 Oct 2012
- Phase
- Phase 4
- 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 20 to 40 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- Healthy male and female subjects
- Age 20-40
- BMI 20-25 mg/m2
Who cannot join
- Hyperlipidemia
- Smoking
- Pregnancy
- Acute infection
- Anaemia
- Taking drugs influencing lipid or glucose metabolism, the immune system or antihypertensive medication
Show all 14Show fewer
- 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
About this study
Official title: 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.
Read the 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.
- Conditions
- Healthy Adults With Normal BMI
- Being tested
- Fat/Inflammation effects
- Keywords
- Healthy adults, Insulin sensitivity
- Medical subject headings
- Insulin Resistance
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Fat/Inflammation effectsBiological
Fat infusion (Intralipid) over 6 hours Fat orally (Soy bean oil) single dose LPS infusion for 10 minutes Glycerol infusion over 6 hours
| Study group | Role | What they receive |
|---|---|---|
| Fat intravenously | Active comparator | Intravenous application of fat Receives: Biological: Fat/Inflammation effects |
| Fat orally | Active comparator | Oral fat load Receives: Biological: Fat/Inflammation effects |
| LPS intravenously | Active comparator | Lipopolysaccharide (LPS; US Standard Reference endotoxin) Receives: Biological: Fat/Inflammation effects |
| Glycerol intravenously | Placebo comparator | Intrevenous glycerol infusion Receives: Biological: Fat/Inflammation effects |
What is being measured
The primary outcome is the main question the study is designed to answer.
Effect of intervention on whole body insulin sensitivity
Measured: 6 hours
Secondary outcomes (2)
Effect of intervention on systemic inflammation
Measured: 1-6 hours
Effect of intervention on cellular immune mechanisms
Measured: 6 hours
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Jan 2010 (estimated)
- Study start15 Mar 2009
- Primary completion15 Sep 2011
- Study completion15 Oct 2012
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Healthy Adults With Normal BMIStudies 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 4
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Enrolment
- 16 participants (actual)
Sponsor and investigators
- Lead sponsor
- German Diabetes Center
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, julia szendrödi, German Diabetes Center
- Investigators
- Michael Roden, Prof., MD, Study director, German Diabetes CenterBettina Nowotny, MD, Principal investigator, German Diabetes Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01054989
- Sponsor's protocol ID
- FIRE-01
- Acronym
- FIRE
- Status last verified
- Aug 2020
- First submitted
- 22 Jan 2010
- Last updated
- 20 Aug 2020
- Results posted
- No
- Data monitoring committee
- Yes
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.
PubMed 25893426Nowotny 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.
PubMed 23454694
Study at a glance
From the registry record, last updated by the sponsor on 20 Aug 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Fat, Inflammation and Insulin Resistance (FIRE-Study)
- ClinicalTrials.gov ID
- NCT01054989
- Acronym / sponsor ID
- FIRE / FIRE-01
- Conditions
- Healthy Adults With Normal BMI
- Keywords
- Healthy adults, Insulin sensitivity
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 16 participants (actual)
- Lead sponsor
- German Diabetes CenterUniversity, hospital or other
- Study start
- 15 Mar 2009 (actual)
- Primary completion
- 15 Sep 2011 (actual)
- Study completion
- 15 Oct 2012 (actual)
- First posted
- 25 Jan 2010 (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 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.
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 design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Fat intravenously | Active comparator | Biological: Fat/Inflammation effectsIntravenous application of fat |
| Fat orally | Active comparator | Biological: Fat/Inflammation effectsOral fat load |
| LPS intravenously | Active comparator | Biological: Fat/Inflammation effectsLipopolysaccharide (LPS; US Standard Reference endotoxin) |
| Glycerol intravenously | Placebo comparator | Biological: Fat/Inflammation effectsIntrevenous glycerol infusion |
Who may qualify
- Ages
- 20 to 40 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (3 listed)
- Healthy male and female subjects
- Age 20-40
- BMI 20-25 mg/m2
Key exclusion criteria (14 listed)
- Hyperlipidemia
- Smoking
- Pregnancy
- Acute infection
- Anaemia
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 |
|---|---|---|
| Fat/Inflammation effectsFat infusion (Intralipid) over 6 hours Fat orally (Soy bean oil) single dose LPS infusion for 10 minutes Glycerol infusion over 6 hours | Biological | Fat intravenously, Fat orally, Glycerol intravenously, LPS intravenously |
Primary outcome
Effect of intervention on whole body insulin sensitivity
Time frame: 6 hours
2 secondary outcomes
Effect of intervention on systemic inflammation
Time frame: 1-6 hours
Effect of intervention on cellular immune mechanisms
Time frame: 6 hours
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 20 Aug 2020.
- Derived from this study: PubMed 25893426Ziegler 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.
- Derived from this study: PubMed 23454694Nowotny 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.
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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.
Michael Roden, Prof., MD study director
German Diabetes Center
Bettina Nowotny, MD principal investigator
German Diabetes Center
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Fat/Inflammation effects in people with Healthy Adults With Normal BMI, run by German Diabetes Center.
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 3 inclusion and 14 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 20 Aug 2020. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
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?
Effect of intervention on whole body insulin sensitivity (time frame: 6 hours). 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 NCT01054989, which also lists 2 linked publications.
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 20 Aug 2020.