Metabolic SyndromeNCT00579436
Effects of Fish Oils on Inflammation and Insulin Resistance
A study testing omega-3 fatty acid in people with Metabolic Syndrome and Insulin Resistance, run by Philip Kern at 1 site in United States.
Trial summary
The purpose of this study is to determine whether improvement in fat and muscle metabolism after the treatment with Omacor (fish oils) provides insight into the link between obesity, fat and muscle function leading to metabolic syndrome, which is a risk factor for heart disease and diabetes. Read more about this study
- Who is it for?
- Ages 35 to 65 yearsHealthy volunteers can take part
- Conditions the study is for
- Metabolic Syndrome, Insulin Resistance
- What is being tested?
- omega-3 fatty acid
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 33 participants
- Where
- 1 siteUnited States
- Study dates
- Jan 2007to 15 Jan 2015
- Phase
- Interventional
- 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 35 to 65 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- BMI 27-45 kg/m2
- age 35-65 years
- abnormal carbohydrate metabolism
Who cannot join
- triglycerides over 700 mg/dl
- renal disease
- liver disease
- congestive heart failure
- history of heart disease or stroke
- chronic aspirin or NSAID use (anti-coagulant)
Show all 9Show fewer
- history of a bleeding disorder
- use of statins, fibrates, ACE inhibitors, angiotensin II receptor blockers and glucocorticoids
- diet heavy in omega-3 fatty acids (salmon, sardines, flaxseeds)
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Kentucky Medical Cener
Lexington, Kentucky, 40475
About this study
The purpose of this study is to determine whether improvement in fat and muscle metabolism after the treatment with Omacor (fish oils) provides insight into the link between obesity, fat and muscle function leading to metabolic syndrome, which is a risk factor for heart disease and diabetes.
Read the detailed description
The development of type 2 diabetes (T2DM) represents a complex series of events, involving abnormalities in adipose tissue lipid distribution and insulin action. Along with an increase in adipose tissue mass is an increase in inflammation brought about by macrophages that infiltrate adipose tissue. These macrophages express inflammatory cytokines such as tumor necrosis factor (TNF) and Interleukin -6 (IL-6) which are correlated with insulin resistance and metabolic syndrome, and suggest that metabolic syndrome and diabetes are conditions characterized by a state of chronic, low-grade inflammation. Thiazolidinediones (TZDs) improve insulin sensitivity via activation of peroxisome proliferator-activated receptor (PPAR) , and there is much evidence that PPAR agonists also have anti-inflammatory properties.
Fish oils are rich sources of Omega-3 fatty acids and there is a large literature on the potential benefits of fish oils on lowering serum triglycerides, cardiovascular protection, and immune modulation, and there is evidence that fish oils also activate PPAR . Hence, the focus of this study will be on subjects with insulin resistance and metabolic syndrome, but who do not yet have diabetes. We plan to treat insulin resistant subjects with fish oils and ask the following questions.
Hypothesis 1. The treatment of insulin resistant subjects with fish oils will reduce adipose tissue inflammation.
Aim 1. From blood samples drawn before and after treatment, we will measure levels of circulating inflammatory cytokines.
Aim 2. Adipose tissue biopsies will be performed before and after fish oil treatment. From the adipose biopsies, we will quantitate cytokine expression, macrophage number, and we will look for evidence of macrophage apoptosis.
Aim 3. We will determine whether fish oil treatment increases the adipose tissue secretion and serum level of the high molecular weight form of adiponectin.
Hypothesis 2. The reduction in inflammatory markers occurs through an activation of PPAR by the fish oils.
Aim 4. Adipose tissue and macrophages will be treated in vitro with fish oils in the presence and absence of a PPAR inhibitor. We will determine whether fish oils stimulate the secretion of the high molecular weight adiponectin isoform from adipose tissue and whether they induce apoptosis from macrophages, and whether this process is inhibited by the PPAR inhibitor.
Hypothesis 3. Fish oils improve peripheral insulin sensitivity through a reduction in intramyocellular lipid, and an improvement in muscle insulin signal transduction.
Aim 5. Before and after treatment with fish oils, insulin sensitivity will be measured, along with intramyocellular lipid and genes involved in insulin action and muscle lipid oxidation.
- Conditions
- Metabolic Syndrome, Insulin Resistance
- Being tested
- omega-3 fatty acid, placebo
- Keywords
- inflammation, obesity, diabetes
- Medical subject headings
- Metabolic Syndrome, Insulin Resistance, Inflammation, Obesity, Diabetes Mellitus
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
omega-3 fatty acidDrug
Also called Lovaza
4g of omega-3 fatty acid daily by mouth for 12 weeks.
placeboDrug
4 inert capsules daily by mouth for 12 weeks.
| Study group | Role | What they receive |
|---|---|---|
| Fish oil group | Active comparator | 4g Lovaza (omega-3 fatty acid) daily. Receives: Drug: omega-3 fatty acid |
| Control group | Placebo comparator | placebo (4 non-active capsules daily) Receives: Drug: placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Baseline Adipocyte Size
Prior to starting the fish oil regiment, participants will undergo an incisional abdominal biopsy to remove approximately 4g of adipose tissue to determine adipocyte size
Measured: baseline
Adipocyte Size After Fish Oil Treatment
After completing the fish oil regiment, participant will undergo an incisional abdominal biopsy to remove approximately 4g of adipose tissue to determine individual adipocyte size
Measured: week 12
Secondary outcomes (2)
Baseline Insulin Resistance
Insulin sensitivity (Si) was measured with a frequently sampled intravenous glucose tolerance test. Participants received a bolus of glucose at Time Zero, then a bolus of insulin 20 minutes later. Blood was collected through an IV catheter at multiple time points over the course of 4 hours. Glucose levels were plotted on a time course curve and analyzed using the MIDMOD algorithm.
Measured: baseline
Insulin Resistance After Fish Oil Regiment
Insulin sensitivity (Si) was measured with a frequently sampled intravenous glucose tolerance test. Participants received a bolus of glucose at Time Zero, then a bolus of insulin 20 minutes later. Blood was collected through an IV catheter at multiple time points over the course of 4 hours. Glucose and Insulin levels will be plotted on a time course curve and analyzed using the MINMOD algorithm.
Measured: week 12
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Dec 2007 (estimated)
- Study startJan 2007
- Primary completion27 Mar 2013
- Study completion15 Jan 2015
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.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Metabolic SyndromeStudies 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 N/A
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 33 participants (actual)
Sponsor and investigators
- Lead sponsor
- Philip Kern
- Sponsor type
- University, hospital or other
- Collaborators
- GlaxoSmithKline, National Institutes of Health (NIH), National Center for Research Resources (NCRR)
- Responsible party
- Sponsor-investigator, Philip Kern, University of Kentucky
- Investigators
- Philip A. Kern, M.D., Principal investigator, University of Kentucky
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00579436
- Sponsor's protocol ID
- 74457
- Other IDs
- P20RR021954
- Status last verified
- Apr 2018
- First submitted
- 20 Dec 2007
- Last updated
- 16 May 2018
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Spencer M, Finlin BS, Unal R, Zhu B, Morris AJ, Shipp LR, Lee J, Walton RG, Adu A, Erfani R, Campbell M, McGehee RE Jr, Peterson CA, Kern PA. Omega-3 fatty acids reduce adipose tissue macrophages in human subjects with insulin resistance. Diabetes. 2013 May;62(5):1709-17. doi: 10.2337/db12-1042. Epub 2013 Jan 17.
PubMed 23328126
Study at a glance
From the registry record, last updated by the sponsor on 16 May 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effects of Fish Oils on Inflammation and Insulin Resistance
- ClinicalTrials.gov ID
- NCT00579436
- Acronym / sponsor ID
- 74457
- Conditions
- Metabolic Syndrome, Insulin Resistance
- Keywords
- inflammation, obesity, diabetes
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 33 participants (actual)
- Lead sponsor
- Philip KernUniversity, hospital or other
- Collaborators
- GlaxoSmithKline, National Institutes of Health (NIH), National Center for Research Resources (NCRR)
- Study start
- Jan 2007
- Primary completion
- 27 Mar 2013 (actual)
- Study completion
- 15 Jan 2015 (actual)
- First posted
- 24 Dec 2007 (estimated)
- Results
- Posted 16 May 2018
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 determine whether improvement in fat and muscle metabolism after the treatment with Omacor (fish oils) provides insight into the link between obesity, fat and muscle function leading to metabolic syndrome, which is a risk factor for heart disease and diabetes.
Detailed description
The development of type 2 diabetes (T2DM) represents a complex series of events, involving abnormalities in adipose tissue lipid distribution and insulin action. Along with an increase in adipose tissue mass is an increase in inflammation brought about by macrophages that infiltrate adipose tissue. These macrophages express inflammatory cytokines such as tumor necrosis factor (TNF) and Interleukin -6 (IL-6) which are correlated with insulin resistance and metabolic syndrome, and suggest that metabolic syndrome and diabetes are conditions characterized by a state of chronic, low-grade inflammation. Thiazolidinediones (TZDs) improve insulin sensitivity via activation of peroxisome proliferator-activated receptor (PPAR) , and there is much evidence that PPAR agonists also have anti-inflammatory properties.
Fish oils are rich sources of Omega-3 fatty acids and there is a large literature on the potential benefits of fish oils on lowering serum triglycerides, cardiovascular protection, and immune modulation, and there is evidence that fish oils also activate PPAR . Hence, the focus of this study will be on subjects with insulin resistance and metabolic syndrome, but who do not yet have diabetes. We plan to treat insulin resistant subjects with fish oils and ask the following questions.
Hypothesis 1. The treatment of insulin resistant subjects with fish oils will reduce adipose tissue inflammation.
Aim 1. From blood samples drawn before and after treatment, we will measure levels of circulating inflammatory cytokines.
Aim 2. Adipose tissue biopsies will be performed before and after fish oil treatment. From the adipose biopsies, we will quantitate cytokine expression, macrophage number, and we will look for evidence of macrophage apoptosis.
Aim 3. We will determine whether fish oil treatment increases the adipose tissue secretion and serum level of the high molecular weight form of adiponectin.
Hypothesis 2. The reduction in inflammatory markers occurs through an activation of PPAR by the fish oils.
Aim 4. Adipose tissue and macrophages will be treated in vitro with fish oils in the presence and absence of a PPAR inhibitor. We will determine whether fish oils stimulate the secretion of the high molecular weight adiponectin isoform from adipose tissue and whether they induce apoptosis from macrophages, and whether this process is inhibited by the PPAR inhibitor.
Hypothesis 3. Fish oils improve peripheral insulin sensitivity through a reduction in intramyocellular lipid, and an improvement in muscle insulin signal transduction.
Aim 5. Before and after treatment with fish oils, insulin sensitivity will be measured, along with intramyocellular lipid and genes involved in insulin action and muscle lipid oxidation.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Fish oil group | Active comparator | Drug: omega-3 fatty acid4g Lovaza (omega-3 fatty acid) daily. |
| Control group | Placebo comparator | Drug: placeboplacebo (4 non-active capsules daily) |
Who may qualify
- Ages
- 35 to 65 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- BMI 27-45 kg/m2
- age 35-65 years
- abnormal carbohydrate metabolism
Key exclusion criteria (9 listed)
- triglycerides over 700 mg/dl
- renal disease
- liver disease
- congestive heart failure
- history of heart disease or stroke
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 |
|---|---|---|
| omega-3 fatty acidAlso: Lovaza4g of omega-3 fatty acid daily by mouth for 12 weeks. | Drug | Fish oil group |
| placebo4 inert capsules daily by mouth for 12 weeks. | Drug | Control group |
Primary outcome
Baseline Adipocyte Size
Time frame: baseline
Prior to starting the fish oil regiment, participants will undergo an incisional abdominal biopsy to remove approximately 4g of adipose tissue to determine adipocyte size
Adipocyte Size After Fish Oil Treatment
Time frame: week 12
After completing the fish oil regiment, participant will undergo an incisional abdominal biopsy to remove approximately 4g of adipose tissue to determine individual adipocyte size
2 secondary outcomes
Baseline Insulin Resistance
Time frame: baseline
Insulin Resistance After Fish Oil Regiment
Time frame: week 12
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 May 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 23328126Spencer M, Finlin BS, Unal R, Zhu B, Morris AJ, Shipp LR, Lee J, Walton RG, Adu A, Erfani R, Campbell M, McGehee RE Jr, Peterson CA, Kern PA. Omega-3 fatty acids reduce adipose tissue macrophages in human subjects with insulin resistance. Diabetes. 2013 May;62(5):1709-17. doi: 10.2337/db12-1042. Epub 2013 Jan 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.
Philip A. Kern, M.D. principal investigator
University of Kentucky
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing omega-3 fatty acid in people with Metabolic Syndrome and Insulin Resistance, run by Philip Kern 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 3 inclusion and 9 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 16 May 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 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. 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.
Are results available for this study?
Yes. Results are posted in the registry (first posted 16 May 2018). 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?
Baseline Adipocyte Size (time frame: baseline). The study lists 2 primary outcomes in all. 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 NCT00579436, 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 16 May 2018.