Metabolic SyndromePhase 4NCT00286234
Niacin, N-3 Fatty Acids and Insulin Resistance
A Phase 4 study testing omega-3 acid ethyl esters, extended release niacin and combined treatment in people with Metabolic Syndrome and Hypertriglyceridemia, run by University of South Dakota at 1 site in United States.
Trial summary
This research study is being conducted to test the effects of two drugs on blood lipids (cholesterol and triglycerides) and blood sugar (glucose) levels in patients with diabetes or "pre-diabetes" (both of which have a condition called "insulin-resistance"). Read more about this study
- Who is it for?
- Ages 40 to 69 years
- Conditions the study is for
- Metabolic Syndrome, Hypertriglyceridemia
- What is being tested?
- omega-3 acid ethyl esters, extended release niacin and combined treatment
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 68 participants
- Where
- 1 siteUnited States
- Study dates
- Oct 2007to Dec 2008
- Phase
- Phase 4
- 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 40 to 69 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 40 and 69 years of age Male or female (without hormonal cycling as described below) BMI > 25 Fasting serum triglycerides > 150 mg/dL Ratio of TG/HDL-C > 3.5
Who cannot join
- BMIs > 40 kg/m2 TG > 750 mg/dL HDL-C < 10 mg/dL Presence of other secondary causes of dyslipidemia or hyperglycemia such as hepatic, renal, thyroid or other endocrine diseases History of hypersensitivity to niacin or fish oils History of gout, hepatitis, peptic ulcer or cardiovascular disease Presence of diabetes mellitus, whether controlled by diet or drugs. (We will eliminate subjects with undiagnosed diabetes by screening for fasting glucose > 126 mg/dL) Use of any dietary supplements providing more than 50 mg of niacin or 100 mg of n-3 FA Use of any herbal preparations or weight-loss products Taking any lipid-lowering drugs for at least four weeks prior to screening for the study Medically-required treatment with nitrates, calcium channel blockers, or adrenergic blocking agents (per the Niaspan package insert) Hemoglobin < 12 g/dL (owing to the significant amount of blood being drawn) LDL-C > 145 mg/dL. (This restriction will prevent the randomization of any subject whose LDL-C levels, if assigned to an n-3 FA group, might rise by 10% and thus exceed 160 mg/dL) Known substance abuse Participation in a clinical drug trial anytime during the 30 days prior to screening Anyone whom the investigators judge to be a poor candidate
Trial locations and contacts
1 site in 1 country.
United States1 site
Sanford Clinic Clinical Research Services
Sioux Falls, South Dakota, 57105
About this study
This research study is being conducted to test the effects of two drugs on blood lipids (cholesterol and triglycerides) and blood sugar (glucose) levels in patients with diabetes or "pre-diabetes" (both of which have a condition called "insulin-resistance"). These products are Niaspan (extended release nicotinic acid) and Omacor (omega-3 acid ethyl esters). We hypothesize that the combination of Niaspan and Omacor will reduce serum triglyceride levels, increase HDL-cholesterol levels and do so without altering glucose levels.
Read the detailed description
The insulin resistance syndrome (IRS) afflicts approximately 25% of the US adult population. Its principal components include some or all of the following: central obesity, elevated triglyceride levels, decreased high density lipoprotein cholesterol (HDL-C) levels, a preponderance of small, dense low density lipoprotein (LDL) particles, hyperglycemia, hypertension, and increased thrombotic tendency. Subjects with the IRS are at increased risk for type 2 diabetes and/or coronary heart disease (CHD). While lifestyle changes (diet and exercise) often improve many of the manifestations of the IRS, pharmacotherapy is often needed to normalize individual components.
In recent studies from our laboratory, niacin and fish oil (n-3 fatty acids, FA) used in combination in insulin resistant individuals led to an expected improved the lipid phenotype (reduced triglycerides, increased HDL-C, and fewer, small, dense LDL particles). What was not expected, however, was that an important marker of adipose tissue insulin resistance - meal-induced suppression of free fatty acid (FFA) flux - would be improved as well. Further, knowing that these agents (given as monotherapy) have been reported to worsen glycemia in diabetic subjects, we were surprised to find no significant deterioration in glycemic control. Further preliminary studies in patients with poorly-controlled type 2 diabetes confirmed the ability of this combination of over-the-counter natural agents to significantly improve the lipid profile without adverse effects on glycemia.
Our working hypothesis is that excessive FFA flux from adipose tissue raises serum triglyceride concentrations and leads to other manifestations of the IRS. FFA flux is chronically elevated in insulin resistant subjects due to the insensitivity (i.e., resistance) of their adipocytes to the anti-lipolytic effects of insulin. Released FFA (especially from visceral adipose depots) stimulate hepatic triglyceride synthesis, leading to elevated serum triglyceride levels which subsequently contribute to reduced HDL-C and increased small, dense LDL concentrations. In addition, a high FFA flux can interfere with whole body glucose disposal. If this hypothesis is true, then interventions that improve adipocyte insulin sensitivity may be expected to improve a spectrum of risk factors associated with the insulin resistant state.
Since our preliminary studies support this hypothesis, we propose the following four specific aims which will be tested in a 4-arm, randomized, placebo-controlled, double blind trial:
Specific Aim 1. To test the hypothesis that n-3 FA and niacin (given singly and in combination) will enhance insulin-mediated suppression of FFA rate of appearance (Ra; a surrogate for adipose tissue insulin sensitivity) in insulin resistant subjects.
Specific Aim 2. To test the hypothesis that n-3 FA and niacin (given singly and in combination) will improve insulin sensitivity in insulin resistant subjects.
Specific Aim 3. To test the hypothesis that n-3 FA and niacin (given singly and in combination) will reduce VLDL-triglyceride production rates in insulin resistant subjects.
Specific Aim 4. To test the hypothesis that n-3 FA and niacin (given singly and in combination) will improve the dyslipidemic profile (i.e., reduce serum triglyceride and small, dense LDL concentrations and elevate HDL-C concentrations) in insulin resistant subjects.
At the completion of these studies, we expect to have detailed information on the potential therapeutic efficacy and the kinetic mechanism of action of combined treatment with n-3 FA and niacin. A better understanding of the action of these agents should lead to a clearer appreciation of the relationship between FFA flux and insulin resistance, to more effective therapy for the dyslipidemia of insulin resistance and ultimately to reduced risk for CAD in this burgeoning patient population.
- Conditions
- Metabolic Syndrome, Hypertriglyceridemia
- Being tested
- omega-3 acid ethyl esters, extended release niacin, placebo, combined treatment
- Keywords
- triglycerides, HDL-cholesterol, insulin resistance, omega-3 fatty acids, niacin
- Medical subject headings
- Metabolic Syndrome, Hypertriglyceridemia, Insulin Resistance
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
omega-3 acid ethyl estersDrug
Also called lovaza omacor
4 q qd
extended release niacinDrug
Also called niaspan
2 g qpm
placeboDrug
omacor placebo plus niaspan placebo
omega-3 acid ethyl estersDrug
Also called lovaza omacor
4 g qd
combined treatmentDrug
Also called lovaza, omacor, niaspan
omega-3 acid ethyl esters 4 g qd and extended release niacin, titrate up to 2 g Qpm
| Study group | Role | What they receive |
|---|---|---|
| 1 | Placebo comparator | Dual placebo Receives: Drug: placebo |
| 2 | Experimental | niaspan Receives: Drug: extended release niacin |
| 3 | Experimental | lovaza Receives: Drug: omega-3 acid ethyl esters |
| 4 | Experimental | combined therapy Receives: Drug: combined treatment |
What is being measured
The primary outcome is the main question the study is designed to answer.
Serum TG
Change From Baseline to 4 Months in Serum Triglycerides
Measured: 4 months
Secondary outcomes (1)
Non-HDL-C
Change From Baseline to 4 Months in Serum Non-HDL cholesterol
Measured: baseline and 4 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Feb 2006 (estimated)
- Study startOct 2007
- Primary completionAug 2008
- Study completionDec 2008
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 (3)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 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 68 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of South Dakota
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, William S. Harris, PhD, FAHA, FNLA, University of South Dakota
- Investigators
- William S Harris, PhD, Principal investigator, Sanford Research/USD
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00286234
- Sponsor's protocol ID
- DK61486 (completed)
- Other IDs
- R01DK061486
- Status last verified
- Sep 2021
- First submitted
- 2 Feb 2006
- Last updated
- 26 Oct 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Savinova OV, Fillaus K, Harris WS, Shearer GC. Effects of niacin and omega-3 fatty acids on the apolipoproteins in overweight patients with elevated triglycerides and reduced HDL cholesterol. Atherosclerosis. 2015 Jun;240(2):520-5. doi: 10.1016/j.atherosclerosis.2015.04.793. Epub 2015 Apr 22.
PubMed 25932792Shearer GC, Pottala JV, Hansen SN, Brandenburg V, Harris WS. Effects of prescription niacin and omega-3 fatty acids on lipids and vascular function in metabolic syndrome: a randomized controlled trial. J Lipid Res. 2012 Nov;53(11):2429-35. doi: 10.1194/jlr.P022392. Epub 2012 Aug 14.
PubMed 22892157Hu S, Shearer GC, Steffes MW, Harris WS, Bostom AG. Once-daily extended-release niacin lowers serum phosphorus concentrations in patients with metabolic syndrome dyslipidemia. Am J Kidney Dis. 2011 Jan;57(1):181-2. doi: 10.1053/j.ajkd.2010.06.029. Epub 2010 Oct 8. No abstract available.
PubMed 20888102
Study at a glance
From the registry record, last updated by the sponsor on 26 Oct 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Niacin, N-3 Fatty Acids and Insulin Resistance
- ClinicalTrials.gov ID
- NCT00286234
- Acronym / sponsor ID
- DK61486 (completed)
- Conditions
- Metabolic Syndrome, Hypertriglyceridemia
- Keywords
- triglycerides, HDL-cholesterol, insulin resistance, omega-3 fatty acids, niacin
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 68 participants (actual)
- Lead sponsor
- University of South DakotaUniversity, hospital or other
- Collaborators
- National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
- Study start
- Oct 2007
- Primary completion
- Aug 2008 (actual)
- Study completion
- Dec 2008 (actual)
- First posted
- 3 Feb 2006 (estimated)
- Results
- Posted 26 Oct 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This research study is being conducted to test the effects of two drugs on blood lipids (cholesterol and triglycerides) and blood sugar (glucose) levels in patients with diabetes or "pre-diabetes" (both of which have a condition called "insulin-resistance"). These products are Niaspan (extended release nicotinic acid) and Omacor (omega-3 acid ethyl esters). We hypothesize that the combination of Niaspan and Omacor will reduce serum triglyceride levels, increase HDL-cholesterol levels and do so without altering glucose levels.
Detailed description
The insulin resistance syndrome (IRS) afflicts approximately 25% of the US adult population. Its principal components include some or all of the following: central obesity, elevated triglyceride levels, decreased high density lipoprotein cholesterol (HDL-C) levels, a preponderance of small, dense low density lipoprotein (LDL) particles, hyperglycemia, hypertension, and increased thrombotic tendency. Subjects with the IRS are at increased risk for type 2 diabetes and/or coronary heart disease (CHD). While lifestyle changes (diet and exercise) often improve many of the manifestations of the IRS, pharmacotherapy is often needed to normalize individual components.
In recent studies from our laboratory, niacin and fish oil (n-3 fatty acids, FA) used in combination in insulin resistant individuals led to an expected improved the lipid phenotype (reduced triglycerides, increased HDL-C, and fewer, small, dense LDL particles). What was not expected, however, was that an important marker of adipose tissue insulin resistance - meal-induced suppression of free fatty acid (FFA) flux - would be improved as well. Further, knowing that these agents (given as monotherapy) have been reported to worsen glycemia in diabetic subjects, we were surprised to find no significant deterioration in glycemic control. Further preliminary studies in patients with poorly-controlled type 2 diabetes confirmed the ability of this combination of over-the-counter natural agents to significantly improve the lipid profile without adverse effects on glycemia.
Our working hypothesis is that excessive FFA flux from adipose tissue raises serum triglyceride concentrations and leads to other manifestations of the IRS. FFA flux is chronically elevated in insulin resistant subjects due to the insensitivity (i.e., resistance) of their adipocytes to the anti-lipolytic effects of insulin. Released FFA (especially from visceral adipose depots) stimulate hepatic triglyceride synthesis, leading to elevated serum triglyceride levels which subsequently contribute to reduced HDL-C and increased small, dense LDL concentrations. In addition, a high FFA flux can interfere with whole body glucose disposal. If this hypothesis is true, then interventions that improve adipocyte insulin sensitivity may be expected to improve a spectrum of risk factors associated with the insulin resistant state.
Since our preliminary studies support this hypothesis, we propose the following four specific aims which will be tested in a 4-arm, randomized, placebo-controlled, double blind trial:
Specific Aim 1. To test the hypothesis that n-3 FA and niacin (given singly and in combination) will enhance insulin-mediated suppression of FFA rate of appearance (Ra; a surrogate for adipose tissue insulin sensitivity) in insulin resistant subjects.
Specific Aim 2. To test the hypothesis that n-3 FA and niacin (given singly and in combination) will improve insulin sensitivity in insulin resistant subjects.
Specific Aim 3. To test the hypothesis that n-3 FA and niacin (given singly and in combination) will reduce VLDL-triglyceride production rates in insulin resistant subjects.
Specific Aim 4. To test the hypothesis that n-3 FA and niacin (given singly and in combination) will improve the dyslipidemic profile (i.e., reduce serum triglyceride and small, dense LDL concentrations and elevate HDL-C concentrations) in insulin resistant subjects.
At the completion of these studies, we expect to have detailed information on the potential therapeutic efficacy and the kinetic mechanism of action of combined treatment with n-3 FA and niacin. A better understanding of the action of these agents should lead to a clearer appreciation of the relationship between FFA flux and insulin resistance, to more effective therapy for the dyslipidemia of insulin resistance and ultimately to reduced risk for CAD in this burgeoning patient population.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| 1 | Placebo comparator | Drug: placeboDual placebo |
| 2 | Experimental | Drug: extended release niacinniaspan |
| 3 | Experimental | Drug: omega-3 acid ethyl esterslovaza |
| 4 | Experimental | Drug: combined treatmentcombined therapy |
Who may qualify
- Ages
- 40 to 69 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (1 listed)
- 40 and 69 years of age Male or female (without hormonal cycling as described below) BMI > 25 Fasting serum triglycerides > 150 mg/dL Ratio of TG/HDL-C > 3.5
Key exclusion criteria (1 listed)
- BMIs > 40 kg/m2 TG > 750 mg/dL HDL-C < 10 mg/dL Presence of other secondary causes of dyslipidemia or hyperglycemia such as hepatic, renal, thyroid or other endocrine diseases History of hypersensitivity to niacin or fish oils History of gout, hepatitis, peptic ulcer or cardiovascular disease Presence of diabetes mellitus, whether controlled by diet or drugs. (We will eliminate subjects with undiagnosed diabetes by screening for fasting glucose > 126 mg/dL) Use of any dietary supplements providing more than 50 mg of niacin or 100 mg of n-3 FA Use of any herbal preparations or weight-loss products Taking any lipid-lowering drugs for at least four weeks prior to screening for the study Medically-required treatment with nitrates, calcium channel blockers, or adrenergic blocking agents (per the Niaspan package insert) Hemoglobin < 12 g/dL (owing to the significant amount of blood being drawn) LDL-C > 145 mg/dL. (This restriction will prevent the randomization of any subject whose LDL-C levels, if assigned to an n-3 FA group, might rise by 10% and thus exceed 160 mg/dL) Known substance abuse Participation in a clinical drug trial anytime during the 30 days prior to screening Anyone whom the investigators judge to be a poor candidate
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 acid ethyl estersAlso: lovaza omacor4 q qd | Drug | 3 |
| extended release niacinAlso: niaspan2 g qpm | Drug | 2 |
| placeboomacor placebo plus niaspan placebo | Drug | 1 |
| omega-3 acid ethyl estersAlso: lovaza omacor4 g qd | Drug | 3 |
| combined treatmentAlso: lovaza, omacor, niaspanomega-3 acid ethyl esters 4 g qd and extended release niacin, titrate up to 2 g Qpm | Drug | 4 |
Primary outcome
Serum TG
Time frame: 4 months
Change From Baseline to 4 Months in Serum Triglycerides
1 secondary outcome
Non-HDL-C
Time frame: baseline and 4 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Oct 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 25932792Savinova OV, Fillaus K, Harris WS, Shearer GC. Effects of niacin and omega-3 fatty acids on the apolipoproteins in overweight patients with elevated triglycerides and reduced HDL cholesterol. Atherosclerosis. 2015 Jun;240(2):520-5. doi: 10.1016/j.atherosclerosis.2015.04.793. Epub 2015 Apr 22.
- Derived from this study: PubMed 22892157Shearer GC, Pottala JV, Hansen SN, Brandenburg V, Harris WS. Effects of prescription niacin and omega-3 fatty acids on lipids and vascular function in metabolic syndrome: a randomized controlled trial. J Lipid Res. 2012 Nov;53(11):2429-35. doi: 10.1194/jlr.P022392. Epub 2012 Aug 14.
- Derived from this study: PubMed 20888102Hu S, Shearer GC, Steffes MW, Harris WS, Bostom AG. Once-daily extended-release niacin lowers serum phosphorus concentrations in patients with metabolic syndrome dyslipidemia. Am J Kidney Dis. 2011 Jan;57(1):181-2. doi: 10.1053/j.ajkd.2010.06.029. Epub 2010 Oct 8. No abstract available.
- Abstract to Published PaperLink provided by the sponsor.
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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.
William S Harris, PhD principal investigator
Sanford Research/USD
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 omega-3 acid ethyl esters, extended release niacin and combined treatment in people with Metabolic Syndrome and Hypertriglyceridemia, run by University of South Dakota 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 1 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 26 Oct 2021. 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.
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?
Yes. Results are posted in the registry (first posted 26 Oct 2021). 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?
Serum TG (time frame: 4 months). 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 NCT00286234, 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 26 Oct 2021.