Insulin SensitivityPhase 4FLAMENCT01736202
Acute Effects of an Oral Fat Load on Skeletal Muscle and Hepatic Insulin Sensitivity
A Phase 4 study testing fat orally in people with Insulin Sensitivity, run by German Diabetes Center at 1 site in Germany.
Trial summary
The development of type 2 diabetes is based on a combination of insulin resistance and beta cell dysfunction. In the last years, elevated FFA were recognized as a key players in the pathogenesis of insulin resistance and type 2 diabetes. Read more about this study
- Who is it for?
- Ages 20 to 40 yearsHealthy volunteers can take part
- Conditions the study is for
- Insulin Sensitivity
- What is being tested?
- fat orally
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 20 participants
- Where
- 1 siteGermany
- Study dates
- Mar 2012to 1 Jan 2022
- 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 kg/m2
Who cannot join
- hyperlipidemia
- smoking
- pregnancy
- allergy against paracetamol/palm oil/canola oil
- contraindication for MRI investigations
- anaemia
Show all 10Show fewer
- taking drugs influencing lipid or glucose metabolism, the immune system or antihypertensive treatment
- M. Meulengracht
- Hepatitis/HIV
- chronic diseases
Trial locations and contacts
1 site in 1 country.
Germany1 site
German Diabetes Center
Düsseldorf, North Rhine-Westphalia, 40225
About this study
Official title: Acute Effects of an Oral Fat Load on Skeletal Muscle and Hepatic Insulin Sensitivity (FLAME-study)
The development of type 2 diabetes is based on a combination of insulin resistance and beta cell dysfunction. In the last years, elevated FFA were recognized as a key players in the pathogenesis of insulin resistance and type 2 diabetes.
The study compares the acute effects of an oral lipid bolus on insulin sensitivity and hepatic glucose metabolism in healthy humans.
Read the detailed description
A dysregulation of lipid metabolism with increased levels of free fatty acids (FFA) represents one key mechanism in the pathogenesis of insulin resistance, which contributes to the development of type 2 diabetes (T2D). In most cases, dyslipidemia is related to obesity and the metabolic syndrome. Not only skeletal muscle glucose uptake, but also hepatic glucose fluxes are altered in insulin resistant states. In obese and T2D subjects, rates of gluconeogenesis (GNG) are increased, but in obese normoglycemic subjects endogenous glucose production (EGP) remains constant because of downregulation of glycogenolysis (GL). However, in T2D subjects, both GNG and GL are elevated, contributing to fasting and postprandial hyperglycemia. Therefore, elevated GNG rates may represent an early event in the pathophysiology of insulin resistance and T2D.
Preliminary studies of our institute show that intravenous lipid infusion with subsequent elevation of FFA results in increased GNG rates without alteration of EGP in lean, non-diabetic subjects. In another recent study we investigated the effects of an oral fat load on hepatic insulin sensitivity. As expected, we did not find any alterations in EGP; however, rates of GNG and GL have not been assessed.
The aim of this study is to analyze the effects of an oral fat load with transiently elevated levels of circulating lipids on hepatic glucose fluxes, especially GNG and GL, to elucidate the role of dietary fat in the induction of insulin resistance in healthy humans.
In this randomized, controlled cross-over study, effects of oral palm oil and canola oil ingestion will be investigated in young, healthy lean subjects. Hepatic glucose fluxes will be assessed by two independent methods, in vivo magnet resonance spectroscopy (MRS) and the deuterated water/acetaminophen method, which also allows for the determination of glycogen cycling rates. Furthermore, hepatic phosphorus metabolites and liver fat content will be monitored by MRS.
- Conditions
- Insulin Sensitivity
- Being tested
- fat orally
- Keywords
- oral fat, 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 orallyBiological
Also called water orally
Oral ingestion of palm oil or canola oil or water at timepoint zero
| Study group | Role | What they receive |
|---|---|---|
| Palm oil orally | Active comparator | oral fat load Receives: Biological: fat orally |
| Canola oil orally | Active comparator | Oral fat load Receives: Biological: fat orally |
| Water orally | Placebo comparator | oral water administration as control Receives: Biological: fat orally |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in rate of glucose disappearance (Rd)
Measurement of whole body insulin sensitivity in a hyperinsulinamic euglicamic clamp with deuterated glucose kinetics
Measured: 6 hours
Secondary outcomes (1)
Change in rate of hepatic endogenous glucose production (EGP)
Measurement of hepatic EGP in a hyperinsulinamic euglicamic clamp with deuterated glucose kinetics
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 posted29 Nov 2012 (estimated)
- Study startMar 2012
- Primary completion1 Jan 2022
- Study completion1 Jan 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Insulin SensitivityStudies 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
- 20 participants (actual)
Sponsor and investigators
- Lead sponsor
- German Diabetes Center
- Sponsor type
- University, hospital or other
- Collaborators
- German Center for Diabetes Research
- Responsible party
- Sponsor
- Investigators
- Michael Roden, Prof., MD, Study director, German Diabetes Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01736202
- Sponsor's protocol ID
- FLAME
- Acronym
- FLAME
- Status last verified
- Jun 2023
- First submitted
- 26 Nov 2012
- Last updated
- 25 Aug 2023
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Sarabhai T, Koliaki C, Mastrototaro L, Kahl S, Pesta D, Apostolopoulou M, Wolkersdorfer M, Bonner AC, Bobrov P, Markgraf DF, Herder C, Roden M. Dietary palmitate and oleate differently modulate insulin sensitivity in human skeletal muscle. Diabetologia. 2022 Feb;65(2):301-314. doi: 10.1007/s00125-021-05596-z. Epub 2021 Oct 26.
PubMed 34704121Sarabhai T, Kahl S, Szendroedi J, Markgraf DF, Zaharia OP, Barosa C, Herder C, Wickrath F, Bobrov P, Hwang JH, Jones JG, Roden M. Monounsaturated fat rapidly induces hepatic gluconeogenesis and whole-body insulin resistance. JCI Insight. 2020 May 21;5(10):e134520. doi: 10.1172/jci.insight.134520.
PubMed 32434996Hernandez EA, Kahl S, Seelig A, Begovatz P, Irmler M, Kupriyanova Y, Nowotny B, Nowotny P, Herder C, Barosa C, Carvalho F, Rozman J, Neschen S, Jones JG, Beckers J, de Angelis MH, Roden M. Acute dietary fat intake initiates alterations in energy metabolism and insulin resistance. J Clin Invest. 2017 Feb 1;127(2):695-708. doi: 10.1172/JCI89444. Epub 2017 Jan 23.
PubMed 28112681
Study at a glance
From the registry record, last updated by the sponsor on 25 Aug 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Acute Effects of an Oral Fat Load on Skeletal Muscle and Hepatic Insulin Sensitivity (FLAME-study)
- ClinicalTrials.gov ID
- NCT01736202
- Acronym / sponsor ID
- FLAME / FLAME
- Conditions
- Insulin Sensitivity
- Keywords
- oral fat, insulin sensitivity
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 20 participants (actual)
- Lead sponsor
- German Diabetes CenterUniversity, hospital or other
- Collaborators
- German Center for Diabetes Research
- Study start
- Mar 2012
- Primary completion
- 1 Jan 2022 (actual)
- Study completion
- 1 Jan 2022 (actual)
- First posted
- 29 Nov 2012 (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 development of type 2 diabetes is based on a combination of insulin resistance and beta cell dysfunction. In the last years, elevated FFA were recognized as a key players in the pathogenesis of insulin resistance and type 2 diabetes.
The study compares the acute effects of an oral lipid bolus on insulin sensitivity and hepatic glucose metabolism in healthy humans.
Detailed description
A dysregulation of lipid metabolism with increased levels of free fatty acids (FFA) represents one key mechanism in the pathogenesis of insulin resistance, which contributes to the development of type 2 diabetes (T2D). In most cases, dyslipidemia is related to obesity and the metabolic syndrome. Not only skeletal muscle glucose uptake, but also hepatic glucose fluxes are altered in insulin resistant states. In obese and T2D subjects, rates of gluconeogenesis (GNG) are increased, but in obese normoglycemic subjects endogenous glucose production (EGP) remains constant because of downregulation of glycogenolysis (GL). However, in T2D subjects, both GNG and GL are elevated, contributing to fasting and postprandial hyperglycemia. Therefore, elevated GNG rates may represent an early event in the pathophysiology of insulin resistance and T2D.
Preliminary studies of our institute show that intravenous lipid infusion with subsequent elevation of FFA results in increased GNG rates without alteration of EGP in lean, non-diabetic subjects. In another recent study we investigated the effects of an oral fat load on hepatic insulin sensitivity. As expected, we did not find any alterations in EGP; however, rates of GNG and GL have not been assessed.
The aim of this study is to analyze the effects of an oral fat load with transiently elevated levels of circulating lipids on hepatic glucose fluxes, especially GNG and GL, to elucidate the role of dietary fat in the induction of insulin resistance in healthy humans.
In this randomized, controlled cross-over study, effects of oral palm oil and canola oil ingestion will be investigated in young, healthy lean subjects. Hepatic glucose fluxes will be assessed by two independent methods, in vivo magnet resonance spectroscopy (MRS) and the deuterated water/acetaminophen method, which also allows for the determination of glycogen cycling rates. Furthermore, hepatic phosphorus metabolites and liver fat content will be monitored by MRS.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Palm oil orally | Active comparator | Biological: fat orallyoral fat load |
| Canola oil orally | Active comparator | Biological: fat orallyOral fat load |
| Water orally | Placebo comparator | Biological: fat orallyoral water administration as control |
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 kg/m2
Key exclusion criteria (10 listed)
- hyperlipidemia
- smoking
- pregnancy
- allergy against paracetamol/palm oil/canola oil
- contraindication for MRI investigations
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 orallyAlso: water orallyOral ingestion of palm oil or canola oil or water at timepoint zero | Biological | Canola oil orally, Palm oil orally, Water orally |
Primary outcome
Change in rate of glucose disappearance (Rd)
Time frame: 6 hours
Measurement of whole body insulin sensitivity in a hyperinsulinamic euglicamic clamp with deuterated glucose kinetics
1 secondary outcome
Change in rate of hepatic endogenous glucose production (EGP)
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 25 Aug 2023.
- Derived from this study: PubMed 34704121Sarabhai T, Koliaki C, Mastrototaro L, Kahl S, Pesta D, Apostolopoulou M, Wolkersdorfer M, Bonner AC, Bobrov P, Markgraf DF, Herder C, Roden M. Dietary palmitate and oleate differently modulate insulin sensitivity in human skeletal muscle. Diabetologia. 2022 Feb;65(2):301-314. doi: 10.1007/s00125-021-05596-z. Epub 2021 Oct 26.
- Derived from this study: PubMed 32434996Sarabhai T, Kahl S, Szendroedi J, Markgraf DF, Zaharia OP, Barosa C, Herder C, Wickrath F, Bobrov P, Hwang JH, Jones JG, Roden M. Monounsaturated fat rapidly induces hepatic gluconeogenesis and whole-body insulin resistance. JCI Insight. 2020 May 21;5(10):e134520. doi: 10.1172/jci.insight.134520.
- Derived from this study: PubMed 28112681Hernandez EA, Kahl S, Seelig A, Begovatz P, Irmler M, Kupriyanova Y, Nowotny B, Nowotny P, Herder C, Barosa C, Carvalho F, Rozman J, Neschen S, Jones JG, Beckers J, de Angelis MH, Roden M. Acute dietary fat intake initiates alterations in energy metabolism and insulin resistance. J Clin Invest. 2017 Feb 1;127(2):695-708. doi: 10.1172/JCI89444. Epub 2017 Jan 23.
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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
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing fat orally in people with Insulin Sensitivity, run by German Diabetes Center 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 3 inclusion and 10 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 Aug 2023. 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. 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?
Change in rate of glucose disappearance (Rd) (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 NCT01736202, which also lists 3 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 25 Aug 2023.