Ectopic LipidsNCT01467193
The Effect of Dietary Fat Load and Physical Exercise on the Flexibility and Partitioning of Ectopic Lipids.
An observational study of Ectopic Lipids and Insulin Sensitivity, run by Insel Gruppe AG, University Hospital Bern at 1 site in Switzerland.
Trial summary
This study aims at assessing the effect of standardized dietary fat load and short-term aerobic exercise on systemic lipolysis, flexibility and partitioning of ectopic fat stores (intramyocellular = IMCL, intrahepatocellular = IHCL, intramyocardial lipids = IMCaL) in relation to FFA in endurance trained athletes and… Read more about this study
- Who is it for?
- Ages 18 to 80 yearsHealthy volunteers can take part
- Conditions the study is for
- Ectopic Lipids, Insulin Sensitivity, Aerobic Exercise
- What is being tested?
- Fat diet and 2h standardized aerobic exercise
- How many people
- 30 participants
- Where
- 1 siteSwitzerland
- Study dates
- Aug 2011to May 2014
- Phase
- Observational
- 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 80 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Study population: Athletes:Endurance trained athletes: minimal >50 mlO2/KG body weight GH-deficient adult patients: NO GH-replacement therapy during the last 6 months Sedentary controls: age, BMI, Gender and waist matched (to the growth hormone deficient patients) healthy control subjects
Who may be able to join
- Male and female patients >18 years old
- Capable to exercise for 120 minutes on a treadmill
- Willingness to participate in the study and to give written consent.
- Normal ECG during ergometry
- Specific for Athletes: VO2max> 50 ml/kg/min
- Specific for GHD patients: no GH substitution in the last 6 months
- Specific for sedentary controls: Matched the GHD patients for age, gender, BMI and waist
Who cannot join
- Abnormal liver or renal function
- Active neoplasia
- Severe cardiovascular disease (unstable coronary artery disease, heart failure NYHA III-IV)
- Haemophilia
- Inability to exercise
- Contraindications to exposure to a 3 T magnetic field
Show all 11Show fewer
- Abnormal ECG during ergometry
- Women in childbearing age unless on a continuous contraceptive therapy or surgically sterilized
- Depression, psychosis and other severe personality disorders
- Pregnant women
- Excessive alcohol consumption (>60g/d) or drug abuse
Trial locations and contacts
1 site in 1 country.
Switzerland1 site
Department of Endocrinology, Diabetes and Clinical Nutrition, University Hospital Bern
Bern, 3010
About this study
This study aims at assessing the effect of standardized dietary fat load and short-term aerobic exercise on systemic lipolysis, flexibility and partitioning of ectopic fat stores (intramyocellular = IMCL, intrahepatocellular = IHCL, intramyocardial lipids = IMCaL) in relation to FFA in endurance trained athletes and hypopituitary patients compared to sedentary healthy control subjects.
Exercise is a powerful stimulation for growth hormone (GH) secretion in health. A standardised exercise test can, therefore, be discriminative for the diagnosis of GH-deficiency in adults. This will be assessed.
Read more
Hypothesis (ectopic fat stores)
- Ectopic fats stores are flexible fuel stores and are influenced by diet and physical activity.FFA availability may play an important regulatory role.
- There is a tissue specific partitioning of triglycerides and/or FFA among non-adipose organs after fat load and physical exercise
- The flexibility of ectopic fat stores is related to insulin sensitivity
- Lipolytic and anti-lipolytic hormones are critical for regulating FFA availability (at rest or during exercise) and therefore also for the regulation of ectopic fat stores.
- GH is a lipolytica hormone. Lack of GH in adulthood is related to decreased FFA availability thereby influencing ectopic lipid stores Hypothesis diagnosis of GHD
- A short intensive physical exercise shows a good discriminative power to diagnose GHD.
Read the detailed description
Background
Obesity, in particular visceral obesity, is associated with impaired insulin action on target tissues (insulin resistance or metabolic syndrome) that, in turn, is related to an increased risk for cardiovascular mortality and morbidity. Pathophysiological mechanism remains unclear. Interventions in patients with impaired glucose tolerance/impaired fasting glucose have consistently demonstrated that by increasing physical activity and reducing calorie intake the risk to convert to frank type 2 diabetes is decreased, even more efficiently than by early medical therapy with metformin.
Physically inactive and overweight subjects do not only store the excess of fat in the intra-abdominal or subcutaneous department but also in non-adipose tissue (="ectopic" tissues), such also skeletal muscle, liver and myocardium, also called intramyocellular lipids (IMCL), intrahepatocellular lipids (IHCL) and intramyocardial lipids (IMCaL).This ectopic lipid accumulation occurs either by increased free fatty acids (FFA) uptake, increase synthesis in the involved tissues or reduced FFA oxidation.
The relative contribution of these factors to ectopic lipid accumulation varies in different physiological conditions (i.e. physical exercise, fasting, postprandial condition) and in different tissues. In addition, it may be influenced by hormones that regulate lipid metabolism. There is increasing evidence that ectopic fat and its intermediate metabolites interfere with insulin signalling, thereby contributing to the impaired insulin action on target tissues such as liver and skeletal muscle. It has been well showed that high fat oxydation capacity allows to keep a lower lipolytic activity and therefore low levels of lipolyse degradation products. Strong evidence is accumulating that these intermediates interact with insulin signalling finally resulting in insulin resistance.
There is still scarce data about the behaviour of ectopic fat stores in the presence of positive(nutritional fat excess) or negative energy balance (physical activity) and the role of hormones in regulating these fat depots.
Additionally,we have previously shown that GH values obtained during a 2h standardized aerobic exercise of moderate intensity revealed a high diagnostic accuracy in predicting severe GHD in adult individuals. Whether a shorter exercise on higher intensity may lead to comparable results has to be assessed.
Objective
The study aims to comprehensively assess the flexibility and partitioning of ectopic fat deposition and to define the role of relevant hormones (especially GH and insulin) in relation to the availability of FFAs as well as their role in the process of ectopic fat deposition and consumption. Another objective is to investigate the role of a standardized fat load and aerobic exercise on IMCaL.
Methods
Using the two-step hyperinsulinaemic-euglycaemic clamp technique hepatic and peripheral insulin sensitivity is assessed.
Lipid depots (skeletal muscle and liver) are repeatedly measured by MR-spectroscopy, subcutaneous and visceral fat mass by whole body MR-imaging.
Exercise capacity ist measured on a bicycle (incl. spiroergometry). Counterregulatory hormones, glucose and free fatty acids are measured during a 2h physical exercise at 50-60 VO2max.
Blood samples to evaluate GH will be taken immediately before and after the Vo2 max-test, as well as 15, 30 and 45minutes after the end of the exercise test.
- Conditions
- Ectopic Lipids, Insulin Sensitivity, Aerobic Exercise, Fat Load, Growth Hormone Deficiency
- Being tested
- Fat diet, 2h standardized aerobic exercise
- Medical subject headings
- Insulin Resistance, Dwarfism, Pituitary
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Fat dietDietary supplement
Instructions for a high fat diet will be given at the end of visit 2. This consists of the usual food intake with a supplementary fat intake of 0.75g fat/kg BW, administered as 3 additional snacks. These snacks will be distributed in pre-packed bags. A food diary will be kept. All arms will receive this diet during the 3 days preceding the clamp.
2h standardized aerobic exerciseOther
Aerobic (50-60% of Vo2 max) standardized exercise on a bicycle during 2 hours
| Study group | Role | What they receive |
|---|---|---|
| 1 | Endurance trained athletes: minimal >50 mlO2/KG body weight | |
| 2 | Sedentary healthy control subjects: age, BMI, Gender and waist matched (to the growth hormone deficient patients) | |
| 3 | GHD patients without a GH substitution therapy in the last 6 months Receives: Dietary Supplement: Fat diet; Other: 2h standardized aerobic exercise |
What is being measured
The primary outcome is the main question the study is designed to answer.
Flexibility of IMCaL, IMCL and IHCL (fat load and exercise)
Measured: Year 1 to 4
Secondary outcomes (3)
Determination of visceral fat mass by MRI
Measured: Year 1 to 4
Determination of peripheral and hepatic insulin sensitivity by two step hyperinsulinemic euglycemic clamp
Measured: Year 1 to 3
maximal exercise capacity
Measured: Year 1 to 3
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Nov 2011 (estimated)
- Study startAug 2011
- Primary completionMay 2014
- Study completionMay 2014
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 Ectopic LipidsStudies of the same condition, open and under way.
- More trials run by Insel Gruppe AG, University Hospital BernThe sponsor's other registered studies.
- 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
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 30 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Insel Gruppe AG, University Hospital Bern
- Sponsor type
- University, hospital or other
- Collaborators
- Swiss National Science Foundation
- Investigators
- Emanuel Christ, Prof. Dr med. MD, PhD, Principal investigator, Division of Endocrinology, Diabetes and Clinical Nutrition, University Hospital Bern
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01467193
- Sponsor's protocol ID
- 234/10
- Status last verified
- Oct 2018
- First submitted
- 3 Nov 2011
- Last updated
- 9 Oct 2018
- Results posted
- No
- Data monitoring committee
- No
Publications
Zueger T, Alleman S, Christ ER, Stettler C. Exercise-induced GH secretion in the assessment of GH deficiency in adult individuals. Eur J Endocrinol. 2011 Nov;165(5):723-8. doi: 10.1530/EJE-11-0539. Epub 2011 Aug 19.
PubMed 21856788Loher H, Jenni S, Bucher J, Krusi M, Kreis R, Boesch C, Christ E. Impaired repletion of intramyocellular lipids in patients with growth hormone deficiency after a bout of aerobic exercise. Growth Horm IGF Res. 2018 Oct-Dec;42-43:32-39. doi: 10.1016/j.ghir.2018.08.001. Epub 2018 Aug 17.
PubMed 30153529
Study at a glance
From the registry record, last updated by the sponsor on 9 Oct 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Effect of Dietary Fat Load and Physical Exercise on the Flexibility and Partitioning of Ectopic Lipids.
- ClinicalTrials.gov ID
- NCT01467193
- Acronym / sponsor ID
- 234/10
- Conditions
- Ectopic Lipids, Insulin Sensitivity, Aerobic Exercise, Fat Load, Growth Hormone Deficiency
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 30 participants (estimated)
- Lead sponsor
- Insel Gruppe AG, University Hospital BernUniversity, hospital or other
- Collaborators
- Swiss National Science Foundation
- Study start
- Aug 2011
- Primary completion
- May 2014 (actual)
- Study completion
- May 2014 (actual)
- First posted
- 8 Nov 2011 (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.
This study aims at assessing the effect of standardized dietary fat load and short-term aerobic exercise on systemic lipolysis, flexibility and partitioning of ectopic fat stores (intramyocellular = IMCL, intrahepatocellular = IHCL, intramyocardial lipids = IMCaL) in relation to FFA in endurance trained athletes and hypopituitary patients compared to sedentary healthy control subjects.
Exercise is a powerful stimulation for growth hormone (GH) secretion in health. A standardised exercise test can, therefore, be discriminative for the diagnosis of GH-deficiency in adults. This will be assessed.
Hypothesis (ectopic fat stores)
- Ectopic fats stores are flexible fuel stores and are influenced by diet and physical activity.FFA availability may play an important regulatory role.
- There is a tissue specific partitioning of triglycerides and/or FFA among non-adipose organs after fat load and physical exercise
- The flexibility of ectopic fat stores is related to insulin sensitivity
- Lipolytic and anti-lipolytic hormones are critical for regulating FFA availability (at rest or during exercise) and therefore also for the regulation of ectopic fat stores.
- GH is a lipolytica hormone. Lack of GH in adulthood is related to decreased FFA availability thereby influencing ectopic lipid stores Hypothesis diagnosis of GHD
- A short intensive physical exercise shows a good discriminative power to diagnose GHD.
Detailed description
Background
Obesity, in particular visceral obesity, is associated with impaired insulin action on target tissues (insulin resistance or metabolic syndrome) that, in turn, is related to an increased risk for cardiovascular mortality and morbidity. Pathophysiological mechanism remains unclear. Interventions in patients with impaired glucose tolerance/impaired fasting glucose have consistently demonstrated that by increasing physical activity and reducing calorie intake the risk to convert to frank type 2 diabetes is decreased, even more efficiently than by early medical therapy with metformin.
Physically inactive and overweight subjects do not only store the excess of fat in the intra-abdominal or subcutaneous department but also in non-adipose tissue (="ectopic" tissues), such also skeletal muscle, liver and myocardium, also called intramyocellular lipids (IMCL), intrahepatocellular lipids (IHCL) and intramyocardial lipids (IMCaL).This ectopic lipid accumulation occurs either by increased free fatty acids (FFA) uptake, increase synthesis in the involved tissues or reduced FFA oxidation.
The relative contribution of these factors to ectopic lipid accumulation varies in different physiological conditions (i.e. physical exercise, fasting, postprandial condition) and in different tissues. In addition, it may be influenced by hormones that regulate lipid metabolism. There is increasing evidence that ectopic fat and its intermediate metabolites interfere with insulin signalling, thereby contributing to the impaired insulin action on target tissues such as liver and skeletal muscle. It has been well showed that high fat oxydation capacity allows to keep a lower lipolytic activity and therefore low levels of lipolyse degradation products. Strong evidence is accumulating that these intermediates interact with insulin signalling finally resulting in insulin resistance.
There is still scarce data about the behaviour of ectopic fat stores in the presence of positive(nutritional fat excess) or negative energy balance (physical activity) and the role of hormones in regulating these fat depots.
Additionally,we have previously shown that GH values obtained during a 2h standardized aerobic exercise of moderate intensity revealed a high diagnostic accuracy in predicting severe GHD in adult individuals. Whether a shorter exercise on higher intensity may lead to comparable results has to be assessed.
Objective
The study aims to comprehensively assess the flexibility and partitioning of ectopic fat deposition and to define the role of relevant hormones (especially GH and insulin) in relation to the availability of FFAs as well as their role in the process of ectopic fat deposition and consumption. Another objective is to investigate the role of a standardized fat load and aerobic exercise on IMCaL.
Methods
Using the two-step hyperinsulinaemic-euglycaemic clamp technique hepatic and peripheral insulin sensitivity is assessed.
Lipid depots (skeletal muscle and liver) are repeatedly measured by MR-spectroscopy, subcutaneous and visceral fat mass by whole body MR-imaging.
Exercise capacity ist measured on a bicycle (incl. spiroergometry). Counterregulatory hormones, glucose and free fatty acids are measured during a 2h physical exercise at 50-60 VO2max.
Blood samples to evaluate GH will be taken immediately before and after the Vo2 max-test, as well as 15, 30 and 45minutes after the end of the exercise test.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| 1 | – | –Endurance trained athletes: minimal >50 mlO2/KG body weight |
| 2 | – | –Sedentary healthy control subjects: age, BMI, Gender and waist matched (to the growth hormone deficient patients) |
| 3 | – | Dietary Supplement: Fat diet, Other: 2h standardized aerobic exerciseGHD patients without a GH substitution therapy in the last 6 months |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
- Study population
- Athletes:Endurance trained athletes: minimal >50 mlO2/KG body weight GH-deficient adult patients: NO GH-replacement therapy during the last 6 months Sedentary controls: age, BMI, Gender and waist matched (to the growth hormone deficient patients) healthy control subjects
Key inclusion criteria (7 listed)
- Male and female patients >18 years old
- Capable to exercise for 120 minutes on a treadmill
- Willingness to participate in the study and to give written consent.
- Normal ECG during ergometry
- Specific for Athletes: VO2max> 50 ml/kg/min
Key exclusion criteria (11 listed)
- Abnormal liver or renal function
- Active neoplasia
- Severe cardiovascular disease (unstable coronary artery disease, heart failure NYHA III-IV)
- Haemophilia
- Inability to exercise
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 dietInstructions for a high fat diet will be given at the end of visit 2. This consists of the usual food intake with a supplementary fat intake of 0.75g fat/kg BW, administered as 3 additional snacks. These snacks will be distributed in pre-packed bags. A food diary will be kept. All arms will receive this diet during the 3 days preceding the clamp. | Dietary supplement | 3 |
| 2h standardized aerobic exerciseAerobic (50-60% of Vo2 max) standardized exercise on a bicycle during 2 hours | Other | 3 |
Primary outcome
Flexibility of IMCaL, IMCL and IHCL (fat load and exercise)
Time frame: Year 1 to 4
3 secondary outcomes
Determination of visceral fat mass by MRI
Time frame: Year 1 to 4
Determination of peripheral and hepatic insulin sensitivity by two step hyperinsulinemic euglycemic clamp
Time frame: Year 1 to 3
maximal exercise capacity
Time frame: Year 1 to 3
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 9 Oct 2018.
- Results publication: PubMed 21856788Zueger T, Alleman S, Christ ER, Stettler C. Exercise-induced GH secretion in the assessment of GH deficiency in adult individuals. Eur J Endocrinol. 2011 Nov;165(5):723-8. doi: 10.1530/EJE-11-0539. Epub 2011 Aug 19.
- Derived from this study: PubMed 30153529Loher H, Jenni S, Bucher J, Krusi M, Kreis R, Boesch C, Christ E. Impaired repletion of intramyocellular lipids in patients with growth hormone deficiency after a bout of aerobic exercise. Growth Horm IGF Res. 2018 Oct-Dec;42-43:32-39. doi: 10.1016/j.ghir.2018.08.001. Epub 2018 Aug 17.
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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.
Emanuel Christ, Prof. Dr med. MD, PhD principal investigator
Division of Endocrinology, Diabetes and Clinical Nutrition, University Hospital Bern
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Ectopic Lipids and Insulin Sensitivity, run by Insel Gruppe AG, University Hospital Bern at 1 site in Switzerland.
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 7 inclusion and 11 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 9 Oct 2018. 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 Switzerland. 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?
Flexibility of IMCaL, IMCL and IHCL (fat load and exercise) (time frame: Year 1 to 4). 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 NCT01467193, 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 9 Oct 2018.