InflammationNCT00330967
Mechanisms of Insulin Resistance in Humans
An observational study of Inflammation and Insulin Resistance, run by US Department of Veterans Affairs at 1 site in United States.
Trial summary
The Objectives of the study are to: (1)compare the inflammatory response and insulin resistance in skeletal muscles during a systemic infusion of lipid with that during a local infusion of lipid into the femoral artery. Read more about this study
- Who is it for?
- Ages 21 to 65 yearsHealthy volunteers can take part
- Conditions the study is for
- Inflammation, Insulin Resistance
- What is being tested?
- 20% Intralipid
- Type of treatment
- Injection or infusion
- How many people
- 25 participants
- Where
- 1 siteUnited States
- Study dates
- Apr 2006to Aug 2014
- Phase
- Observational
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 21 to 65 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Study population: healthy subjects
Who may be able to join
- two groups of 16 healthy subjects
Who cannot join
- diabetes or impaired glucose tolerance
- peripheral vascular disease
- pulmonary disease
- clinically significant hepatic or renal disease
- triglycerides >200mg/dl
- anemia
- abnormal PT, PTT or INR
- pregnancy or lactation
Trial locations and contacts
1 site in 1 country.
United States1 site
Phoenix VA Health Care System Carl T. Hayden VA Medical Center, Phoenix, AZ
Phoenix, Arizona, 85012
About this study
The Objectives of the study are to: (1)compare the inflammatory response and insulin resistance in skeletal muscles during a systemic infusion of lipid with that during a local infusion of lipid into the femoral artery. which would cause minimal or no systemic hyperlipidemia but local plasma free fatty acid (FFA) concentrations similar to those during the systemic lipid infusion, and (2) determine the inflammatory response and insulin resistance in skeletal muscle during an infusion of lipid into the femoral artery as described above after NF-KB inhibition by high dose salicylate treatment in humans.
Read the detailed description
Insulin resistance in skeletal muscle is a characteristic abnormality in obesity and the metabolic syndrome and a major factor responsible for the development of type 2 diabetes. Although the mechanisms responsible for muscle insulin resistance are largely unclear, lipid oversupply is an important factor. Among numerous potential mechanisms whereby lipid oversupply may cause muscle insulin resistance, current evidence points towards inflammation as being critical. Recent studies in animals, however, indicate that the inflammatory response in skeletal muscles may require the presence of circulating pro-inflammatory factors suggesting that the inflammation induced insulin resistance in skeletal muscles may be a secondary event. More specifically, activation of Nuclear Factor-Kappa B(NF-kB), and inflammatory master switch that drives the production of numerous pro-inflammatory cytokines in fat and liver, has been implicated in causing insulin resistance in skeletal muscles by increasing circulating pro-inflammatory cytokines. In contrast, animal studies have found that activation of NF-KB directly in skeletal muscles has no or little effect on its insulin sensitivity but does produce other abnormalities such as increased proteasome activity. The study shall therefore be undertaken to determine to what extent lipid-induced inflammation and insulin resistance in skeletal muscles requires the presence of circulating proinflammatory factors in humans.
- Conditions
- Inflammation, Insulin Resistance
- Being tested
- 20% Intralipid
- Keywords
- Fat Emulsions, Intravenous, Free Fatty Acids, Glucose Clamp Technique, Inflammation, Insulin Resistance, Muscle, Skeletal, NF-Kappa B
- Medical subject headings
- Inflammation, Insulin Resistance
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
20% IntralipidDrug
lipid infusion
| Study group | Role | What they receive |
|---|---|---|
| Group 1 | healthy subjects Receives: Drug: 20% Intralipid | |
| Group 2 | healthy subjects different from group 1 Receives: Drug: 20% Intralipid |
What is being measured
The primary outcome is the main question the study is designed to answer.
Insulin Signaling With Lipid Infusion
IRS-1 expression in response to femoral lipid infusion in skeletal muscle. Relative protein expression was calculated by densitometry analysis of Western blot bands, normalized to a housekeeping protein, GAPDH, in control and treated groups.
Measured: 4 h
Phos-p38 MAPK Expression With Femoral Lipid and Insulin Infusions
Phosphorylation of p38 MAPK in response to femoral lipid and insulin infusions. phospho-p38 MAPK expression in response to femoral lipid infusion in skeletal muscle. Relative protein expression was calculated by densitometry analysis of Western blots, normalized to a housekeeping protein, GAPDH, of control and treated groups.
Measured: 4 h
p38 MAPK Expression With Femoral Lipid and Insulin Infusions
p38 MAPK expression in response to femoral lipid and insulin infusions in skeletal muscle. Relative protein expression was calculated by densitometry analysis of Western blots, normalized to a housekeeping protein, GAPDH, of control and treated groups.
Measured: 4 h
Phospho-ERK MAPK Expression With Femoral Lipid and Insulin Infusions
Phosphorylation of ERK MAPK in response to femoral lipid and insulin infusions in skeletal muscle. Relative protein expression was calculated by densitometry analysis of Western blots, normalized to a housekeeping protein, GAPDH, of control and treated groups.
Measured: 4 h
ERK MAPK Expression With Femoral Lipid and Insulin Infusions
ERK MAPK expression in response to femoral lipid and insulin infusions in skeletal muscle. Relative protein expression was calculated by densitometry analysis of Western blots, normalized to a housekeeping protein, GAPDH, of control and treated groups.
Measured: 4 h
Phospho-JNK MAPK Expression With Femoral Lipid and Insulin Infusions
Phosphorylation of JNK MAPK in response to femoral lipid and insulin infusions in skeletal muscle. Relative protein expression was calculated by densitometry analysis of Western blots, normalized to a housekeeping protein, GAPDH, of control and treated groups.
Measured: 4 h
JNK MAPK Expression With Femoral Lipid and Insulin Infusions
JNK MAPK expression in response to femoral lipid and insulin infusions in skeletal muscle. Relative protein expression was calculated by densitometry analysis of Western blots, normalized to a housekeeping protein, GAPDH, of control and treated groups.
Measured: 4 h
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 May 2006 (estimated)
- Study startApr 2006
- Primary completionJan 2012
- Study completionAug 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for InflammationStudies 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
- Observational
- Time perspective
- Prospective
- Enrolment
- 25 participants (actual)
Sponsor and investigators
- Lead sponsor
- US Department of Veterans Affairs
- Sponsor type
- US federal agency
- Responsible party
- Sponsor
- Investigators
- Charles C Oh, MD, Principal investigator, Phoenix VA Health Care System Carl T. Hayden VA Medical Center, Phoenix, AZ
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00330967
- Sponsor's protocol ID
- ENDA-029-05F
- Status last verified
- Mar 2015
- First submitted
- 26 May 2006
- Last updated
- 3 Apr 2015
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 3 Apr 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Mechanisms of Insulin Resistance in Humans
- ClinicalTrials.gov ID
- NCT00330967
- Acronym / sponsor ID
- ENDA-029-05F
- Conditions
- Inflammation, Insulin Resistance
- Keywords
- Fat Emulsions, Intravenous, Free Fatty Acids, Glucose Clamp Technique, Inflammation, Insulin Resistance, Muscle, Skeletal, NF-Kappa B
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 25 participants (actual)
- Lead sponsor
- US Department of Veterans AffairsUS federal agency
- Study start
- Apr 2006
- Primary completion
- Jan 2012 (actual)
- Study completion
- Aug 2014 (actual)
- First posted
- 29 May 2006 (estimated)
- Results
- Posted 17 Mar 2015
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The Objectives of the study are to: (1)compare the inflammatory response and insulin resistance in skeletal muscles during a systemic infusion of lipid with that during a local infusion of lipid into the femoral artery. which would cause minimal or no systemic hyperlipidemia but local plasma free fatty acid (FFA) concentrations similar to those during the systemic lipid infusion, and (2) determine the inflammatory response and insulin resistance in skeletal muscle during an infusion of lipid into the femoral artery as described above after NF-KB inhibition by high dose salicylate treatment in humans.
Detailed description
Insulin resistance in skeletal muscle is a characteristic abnormality in obesity and the metabolic syndrome and a major factor responsible for the development of type 2 diabetes. Although the mechanisms responsible for muscle insulin resistance are largely unclear, lipid oversupply is an important factor. Among numerous potential mechanisms whereby lipid oversupply may cause muscle insulin resistance, current evidence points towards inflammation as being critical. Recent studies in animals, however, indicate that the inflammatory response in skeletal muscles may require the presence of circulating pro-inflammatory factors suggesting that the inflammation induced insulin resistance in skeletal muscles may be a secondary event. More specifically, activation of Nuclear Factor-Kappa B(NF-kB), and inflammatory master switch that drives the production of numerous pro-inflammatory cytokines in fat and liver, has been implicated in causing insulin resistance in skeletal muscles by increasing circulating pro-inflammatory cytokines. In contrast, animal studies have found that activation of NF-KB directly in skeletal muscles has no or little effect on its insulin sensitivity but does produce other abnormalities such as increased proteasome activity. The study shall therefore be undertaken to determine to what extent lipid-induced inflammation and insulin resistance in skeletal muscles requires the presence of circulating proinflammatory factors in humans.
Study design
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Group 1 | – | Drug: 20% Intralipidhealthy subjects |
| Group 2 | – | Drug: 20% Intralipidhealthy subjects different from group 1 |
Who may qualify
- Ages
- 21 to 65 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
- Study population
- healthy subjects
Key inclusion criteria (1 listed)
- two groups of 16 healthy subjects
Key exclusion criteria (8 listed)
- diabetes or impaired glucose tolerance
- peripheral vascular disease
- pulmonary disease
- clinically significant hepatic or renal disease
- triglycerides >200mg/dl
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 |
|---|---|---|
| 20% Intralipidlipid infusion | Drug | Group 1, Group 2 |
Primary outcome
Insulin Signaling With Lipid Infusion
Time frame: 4 h
IRS-1 expression in response to femoral lipid infusion in skeletal muscle. Relative protein expression was calculated by densitometry analysis of Western blot bands, normalized to a housekeeping protein, GAPDH, in control and treated groups.
Phos-p38 MAPK Expression With Femoral Lipid and Insulin Infusions
Time frame: 4 h
Phosphorylation of p38 MAPK in response to femoral lipid and insulin infusions. phospho-p38 MAPK expression in response to femoral lipid infusion in skeletal muscle. Relative protein expression was calculated by densitometry analysis of Western blots, normalized to a housekeeping protein, GAPDH, of control and treated groups.
p38 MAPK Expression With Femoral Lipid and Insulin Infusions
Time frame: 4 h
p38 MAPK expression in response to femoral lipid and insulin infusions in skeletal muscle. Relative protein expression was calculated by densitometry analysis of Western blots, normalized to a housekeeping protein, GAPDH, of control and treated groups.
Phospho-ERK MAPK Expression With Femoral Lipid and Insulin Infusions
Time frame: 4 h
Phosphorylation of ERK MAPK in response to femoral lipid and insulin infusions in skeletal muscle. Relative protein expression was calculated by densitometry analysis of Western blots, normalized to a housekeeping protein, GAPDH, of control and treated groups.
ERK MAPK Expression With Femoral Lipid and Insulin Infusions
Time frame: 4 h
ERK MAPK expression in response to femoral lipid and insulin infusions in skeletal muscle. Relative protein expression was calculated by densitometry analysis of Western blots, normalized to a housekeeping protein, GAPDH, of control and treated groups.
Phospho-JNK MAPK Expression With Femoral Lipid and Insulin Infusions
Time frame: 4 h
Phosphorylation of JNK MAPK in response to femoral lipid and insulin infusions in skeletal muscle. Relative protein expression was calculated by densitometry analysis of Western blots, normalized to a housekeeping protein, GAPDH, of control and treated groups.
JNK MAPK Expression With Femoral Lipid and Insulin Infusions
Time frame: 4 h
JNK MAPK expression in response to femoral lipid and insulin infusions in skeletal muscle. Relative protein expression was calculated by densitometry analysis of Western blots, normalized to a housekeeping protein, GAPDH, of control and treated groups.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Apr 2015.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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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.
Charles C Oh, MD principal investigator
Phoenix VA Health Care System Carl T. Hayden VA Medical Center, Phoenix, AZ
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 Inflammation and Insulin Resistance, run by US Department of Veterans Affairs at 1 site in United States.
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 1 inclusion and 8 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 3 Apr 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 United States. 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?
Yes. Results are posted in the registry (first posted 17 Mar 2015). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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 Signaling With Lipid Infusion (time frame: 4 h). The study lists 7 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 3 Apr 2015.