Insulin SensitivityNCT01576250
The Effect of Lowered Physical Activity on Insulin Sensitivity and Lipid and Glucose Metabolism
A study testing unilateral lower limb suspension in people with Insulin Sensitivity, run by Maastricht University Medical Center at 1 site in Netherlands.
Trial summary
The purpose of this study is to investigate the effects of lowered physical activity (resulting in decreased muscle mitochondrial oxidative capacity) alone and together with increased plasma free fatty acid availability (by infusion of a clinically widely used lipid emulsion (Intralipid)) on insulin sensitivity and… Read more about this study
- Who is it for?
- Ages 18 to 35 years, men onlyHealthy volunteers can take part
- Conditions the study is for
- Insulin Sensitivity
- What is being tested?
- unilateral lower limb suspension
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 13 participants
- Where
- 1 siteNetherlands
- Study dates
- Apr 2012to Aug 2013
- Phase
- Interventional
- 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 35 years
- Men only
- Healthy volunteers accepted
- Adult
Who may be able to join
- Men between 18-35 years of age at time of enrolment
- Non smoking
- No recent bone fractures of the limbs
- No cardiovascular medication or other medication
- No family history of thrombosis
- No engagement in programmed exercise for more than two hours a week
- Stable dietary habits
- No contra-indication for MRI
Who cannot join
- Regular smokers
- Participation in other studies
- Female sex
- Recent bone fractures of the limbs
- Medication use
- Cardiovascular disease
Show all 14Show fewer
- Family history of type 2 diabetes mellitus
- Family history of thrombosis
- Contraindications for MRS scans:
- Electronic implants such as pacemakers or neurostimulator
- Iron-containing foreign bodies in eyes or brain
- Some hearing aids and artificial (heart) valves which are contraindicated for MRS
- Claustrophobia
- Participants, who do not want to be informed about unexpected medical findings, or do not wish that their physician will be informed, cannot participate in the study
Trial locations and contacts
1 site in 1 country.
Netherlands1 site
Maastricht University Medical Center
Maastricht, 6200 MD
About this study
Official title: The Effect of Lowered Physical Activity (Induced by Lower Limb Suspension (ULLS)) on Insulin Sensitivity and Lipid and Glucose Metabolism
The purpose of this study is to investigate the effects of lowered physical activity (resulting in decreased muscle mitochondrial oxidative capacity) alone and together with increased plasma free fatty acid availability (by infusion of a clinically widely used lipid emulsion (Intralipid)) on insulin sensitivity and glucose and lipid metabolism. To this end, we will compare skeletal muscle insulin sensitivity and glucose and lipid metabolism (within one subject) after 9 days of immobilization of one leg (unilateral lower limb suspension(ULLS))(decreased muscle mitochondrial oxidative capacity) versus an active control leg (unchanged muscle mitochondrial oxidative capacity). Further, changes in IMCL and fatty acid intermediates will be investigated in the immobilized vs the control leg, and this will be related to insulin sensitivity. The effectiveness of the ULLS intervention will be tested by measuring muscle mitochondrial oxidative capacity in both the immobilized and the control leg. All measurements will be performed both in the immobilized and control leg after 9 days of ULLS.
Read the detailed description
In the Netherlands and worldwide, the number of individuals suffering from obesity and type 2 diabetes mellitus is rising steadily. It is well established that obesity predisposes individuals to accumulation of excessive fat in non-adipose tissues such as the liver, the heart and skeletal muscle (called steatosis or ectopic fat accumulation). Furthermore, in sedentary humans ectopic fat accumulation in skeletal muscle is strongly associated with insulin resistance. However, paradoxically, IntraMyoCellular Lipid (IMCL) content is also increased in highly insulin sensitive endurance trained subjects (known as the athlete's paradox). This is suggesting that IMCL per se is not causative in skeletal muscle insulin resistance. The increased IMCL storage following endurance training serves to match training-induced increase in oxidative capacity and reliance on fat as a substrate during exercise, whereas in obesogenic/diabetogenic conditions the high fat availability is not matched by improved oxidative capacity. It is therefore speculated that under the latter conditions, the lipid intermediates of IMCL metabolism such as diacylglycerol (DAG), ceramides and fatty acyl-CoAs will accumulate and impede cellular insulin signalling. The rate of oxidative capacity is regulated by mitochondria, which are cellular organelles responsible for cellular energy production and cellular metabolism. Therefore, the overall hypothesis of this project is that a low muscle mitochondrial oxidative capacity can lead to muscle fat accumulation and/or accumulation of lipid intermediates when fatty acid availability is high, and this may result in insulin resistance in skeletal muscle.
- Conditions
- Insulin Sensitivity
- Being tested
- unilateral lower limb suspension
- Medical subject headings
- Insulin Resistance
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
unilateral lower limb suspensionOther
This is an intervention study, where each subject will undergo 12 days of unilateral lower limb suspension. Randomly, the dominant or the non-dominant leg of the subject will be suspended by attachment of a sling to a non-rigid ankle brace and to a harness on the upper body and unloaded from all weight bearing. The knee will be slightly flexed at an angle of 130°. Hip, knee and ankle will be fully mobile. The sling will be used during all locomotory activity, and the subjects will use crutches for walking.
| Study group | Role | What they receive |
|---|---|---|
| unilateral lower limb suspension | Experimental | This is an intervention study, where each subject will undergo 12 days of unilateral lower limb suspension. Randomly, the dominant or the non-dominant leg of the subject will be suspended by attachment of a sling to a non-rigid ankle brace and to a harness on the upper body and unloaded from all weight bearing. The knee will be slightly flexed at an angle of 130°. Hip, knee and ankle will be fully mobile. The sling will be used during all locomotory activity, and the subjects will use crutches for walking. Receives: Other: unilateral lower limb suspension |
What is being measured
The primary outcome is the main question the study is designed to answer.
Insulin sensitivity
After 9 days of ULLS a muscle biopsy will be derived before and after a 5 h lipid infusion,from both the immobilized and the control leg. Insulin sensitivity will further be investigated from the skeletal muscle tissue ex vivo.
Measured: after 9 days of ULLS
Secondary outcomes (4)
intramyocellularlipid content
After 9 days of ULLS a muscle biopsy will be derived before and after a 5 h lipid infusion,from both the immobilized and the control leg. Muscle tissue will immediately be frozen and stored for later determination of Intramyocellular lipid content.
Measured: after 9 days of ULLS
Lipid intermediates
After 9 days of ULLS a muscle biopsy will be derived before and after a 5 h lipid infusion,from both the immobilized and the control leg. Lipid intermediates will further be investigated from the skeletal muscle tissue ex vivo.
Measured: after 9 days of ULLS
Lipid metabolism
After 9 days of ULLS a muscle biopsy will be derived before and after a 5 h lipid infusion,from both the immobilized and the control leg. Lipid metabolism will further be investigated from the skeletal muscle tissue ex vivo.
Measured: after 9 days of ULLS
Glucose metabolism
After 9 days of ULLS a muscle biopsy will be derived before and after a 5 h lipid infusion,from both the immobilized and the control leg. Glucose metabolism will further be investigated from the skeletal muscle tissue ex vivo.
Measured: after 9 days of ULLS
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Apr 2012 (estimated)
- Study startApr 2012
- Primary completionAug 2013
- Study completionAug 2013
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Insulin SensitivityStudies of the same condition, open and under way.
- More trials run by Maastricht University Medical CenterThe 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
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 13 participants (actual)
Sponsor and investigators
- Lead sponsor
- Maastricht University Medical Center
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Lena Bilet, Maastricht University Medical Center
- Investigators
- Patrick Schrauwen, Ph.D., Study director, Maastricht University Medical Center (MUMC)Lena Bilet, MSc., Principal investigator, Maastricht University Medical Center (MUMC)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01576250
- Sponsor's protocol ID
- NL38795.068.11/METC 11-3-074
- Status last verified
- May 2015
- First submitted
- 10 Apr 2012
- Last updated
- 28 May 2015
- Results posted
- No
- Data monitoring committee
- No
Publications
Bilet L, Phielix E, van de Weijer T, Gemmink A, Bosma M, Moonen-Kornips E, Jorgensen JA, Schaart G, Zhang D, Meijer K, Hopman M, Hesselink MKC, Ouwens DM, Shulman GI, Schrauwen-Hinderling VB, Schrauwen P. One-leg inactivity induces a reduction in mitochondrial oxidative capacity, intramyocellular lipid accumulation and reduced insulin signalling upon lipid infusion: a human study with unilateral limb suspension. Diabetologia. 2020 Jun;63(6):1211-1222. doi: 10.1007/s00125-020-05128-1. Epub 2020 Mar 17.
PubMed 32185462
Study at a glance
From the registry record, last updated by the sponsor on 28 May 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Effect of Lowered Physical Activity (Induced by Lower Limb Suspension (ULLS)) on Insulin Sensitivity and Lipid and Glucose Metabolism
- ClinicalTrials.gov ID
- NCT01576250
- Acronym / sponsor ID
- NL38795.068.11/METC 11-3-074
- Conditions
- Insulin Sensitivity
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 13 participants (actual)
- Lead sponsor
- Maastricht University Medical CenterUniversity, hospital or other
- Study start
- Apr 2012
- Primary completion
- Aug 2013 (actual)
- Study completion
- Aug 2013 (actual)
- First posted
- 12 Apr 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 purpose of this study is to investigate the effects of lowered physical activity (resulting in decreased muscle mitochondrial oxidative capacity) alone and together with increased plasma free fatty acid availability (by infusion of a clinically widely used lipid emulsion (Intralipid)) on insulin sensitivity and glucose and lipid metabolism. To this end, we will compare skeletal muscle insulin sensitivity and glucose and lipid metabolism (within one subject) after 9 days of immobilization of one leg (unilateral lower limb suspension(ULLS))(decreased muscle mitochondrial oxidative capacity) versus an active control leg (unchanged muscle mitochondrial oxidative capacity). Further, changes in IMCL and fatty acid intermediates will be investigated in the immobilized vs the control leg, and this will be related to insulin sensitivity. The effectiveness of the ULLS intervention will be tested by measuring muscle mitochondrial oxidative capacity in both the immobilized and the control leg. All measurements will be performed both in the immobilized and control leg after 9 days of ULLS.
Detailed description
In the Netherlands and worldwide, the number of individuals suffering from obesity and type 2 diabetes mellitus is rising steadily. It is well established that obesity predisposes individuals to accumulation of excessive fat in non-adipose tissues such as the liver, the heart and skeletal muscle (called steatosis or ectopic fat accumulation). Furthermore, in sedentary humans ectopic fat accumulation in skeletal muscle is strongly associated with insulin resistance. However, paradoxically, IntraMyoCellular Lipid (IMCL) content is also increased in highly insulin sensitive endurance trained subjects (known as the athlete's paradox). This is suggesting that IMCL per se is not causative in skeletal muscle insulin resistance. The increased IMCL storage following endurance training serves to match training-induced increase in oxidative capacity and reliance on fat as a substrate during exercise, whereas in obesogenic/diabetogenic conditions the high fat availability is not matched by improved oxidative capacity. It is therefore speculated that under the latter conditions, the lipid intermediates of IMCL metabolism such as diacylglycerol (DAG), ceramides and fatty acyl-CoAs will accumulate and impede cellular insulin signalling. The rate of oxidative capacity is regulated by mitochondria, which are cellular organelles responsible for cellular energy production and cellular metabolism. Therefore, the overall hypothesis of this project is that a low muscle mitochondrial oxidative capacity can lead to muscle fat accumulation and/or accumulation of lipid intermediates when fatty acid availability is high, and this may result in insulin resistance in skeletal muscle.
Study design
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| unilateral lower limb suspension | Experimental | Other: unilateral lower limb suspensionThis is an intervention study, where each subject will undergo 12 days of unilateral lower limb suspension. Randomly, the dominant or the non-dominant leg of the subject will be suspended by attachment of a sling to a non-rigid ankle brace and to a harness on the upper body and unloaded from all weight bearing. The knee will be slightly flexed at an angle of 130°. Hip, knee and ankle will be fully mobile. The sling will be used during all locomotory activity, and the subjects will use crutches for walking. |
Who may qualify
- Ages
- 18 to 35 years
- Sex
- Male only
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (8 listed)
- Men between 18-35 years of age at time of enrolment
- Non smoking
- No recent bone fractures of the limbs
- No cardiovascular medication or other medication
- No family history of thrombosis
Key exclusion criteria (14 listed)
- Regular smokers
- Participation in other studies
- Female sex
- Recent bone fractures of the limbs
- Medication use
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 |
|---|---|---|
| unilateral lower limb suspensionThis is an intervention study, where each subject will undergo 12 days of unilateral lower limb suspension. Randomly, the dominant or the non-dominant leg of the subject will be suspended by attachment of a sling to a non-rigid ankle brace and to a harness on the upper body and unloaded from all weight bearing. The knee will be slightly flexed at an angle of 130°. Hip, knee and ankle will be fully mobile. The sling will be used during all locomotory activity, and the subjects will use crutches for walking. | Other | unilateral lower limb suspension |
Primary outcome
Insulin sensitivity
Time frame: after 9 days of ULLS
After 9 days of ULLS a muscle biopsy will be derived before and after a 5 h lipid infusion,from both the immobilized and the control leg. Insulin sensitivity will further be investigated from the skeletal muscle tissue ex vivo.
4 secondary outcomes
intramyocellularlipid content
Time frame: after 9 days of ULLS
Lipid intermediates
Time frame: after 9 days of ULLS
Lipid metabolism
Time frame: after 9 days of ULLS
Glucose metabolism
Time frame: after 9 days of ULLS
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 28 May 2015.
- Derived from this study: PubMed 32185462Bilet L, Phielix E, van de Weijer T, Gemmink A, Bosma M, Moonen-Kornips E, Jorgensen JA, Schaart G, Zhang D, Meijer K, Hopman M, Hesselink MKC, Ouwens DM, Shulman GI, Schrauwen-Hinderling VB, Schrauwen P. One-leg inactivity induces a reduction in mitochondrial oxidative capacity, intramyocellular lipid accumulation and reduced insulin signalling upon lipid infusion: a human study with unilateral limb suspension. Diabetologia. 2020 Jun;63(6):1211-1222. doi: 10.1007/s00125-020-05128-1. Epub 2020 Mar 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.
Patrick Schrauwen, Ph.D. study director
Maastricht University Medical Center (MUMC)
Lena Bilet, MSc. principal investigator
Maastricht University Medical Center (MUMC)
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing unilateral lower limb suspension in people with Insulin Sensitivity, run by Maastricht University Medical Center at 1 site in Netherlands.
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 8 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 28 May 2015. 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 Netherlands. 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?
Insulin sensitivity (time frame: after 9 days of ULLS). 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 NCT01576250, which also lists 1 linked publication.
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 28 May 2015.