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Niacin, N-3 Fatty Acids and Insulin Resistance

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00286234
Recruitment Status : Completed
First Posted : February 3, 2006
Last Update Posted : May 1, 2013
Information provided by:
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Brief 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"). 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.

Condition or disease Intervention/treatment Phase
Metabolic Syndrome Hypertriglyceridemia Drug: omega-3 acid ethyl esters Drug: extended release niacin Drug: placebo Drug: combined treatment Phase 4

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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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 10 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Niacin, N-3 Fatty Acids and Insulin Resistance
Study Start Date : October 2007
Actual Primary Completion Date : August 2008
Actual Study Completion Date : December 2008

Resource links provided by the National Library of Medicine

Arm Intervention/treatment
Placebo Comparator: 1
Dual placebo
Drug: placebo
omacor placebo plus niaspan placebo

Experimental: 2
Drug: extended release niacin
2 g qpm
Other Name: niaspan

Experimental: 3
Drug: omega-3 acid ethyl esters
4 q qd
Other Name: lovaza omacor

Drug: omega-3 acid ethyl esters
4 g qd
Other Name: lovaza omacor

Experimental: 4
combined therapy
Drug: combined treatment
omega-3 acid ethyl esters 4 g qd and extended release niacin, titrate up to 2 g Qpm
Other Names:
  • lovaza, omacor
  • niaspan

Primary Outcome Measures :
  1. Serum TG and HDL-C [ Time Frame: baseline and 4 months ]

Secondary Outcome Measures :
  1. Insulin sensitivity, postprandial triglyceridemia, peripheral arterial tonometry [ Time Frame: baseline and 4 months ]

Information from the National Library of Medicine

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Ages Eligible for Study:   40 Years to 69 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

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

Exclusion Criteria:

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00286234

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United States, South Dakota
Sanford Clinic Clinical Research Services
Sioux Falls, South Dakota, United States, 57105
Sponsors and Collaborators
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
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Principal Investigator: William S Harris, PhD Sanford Research/USD

Publications automatically indexed to this study by Identifier (NCT Number):
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Responsible Party: William S. Harris, Sanford Research/USD Identifier: NCT00286234     History of Changes
Other Study ID Numbers: DK61486 (completed)
First Posted: February 3, 2006    Key Record Dates
Last Update Posted: May 1, 2013
Last Verified: April 2013
Keywords provided by National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK):
insulin resistance
omega-3 fatty acids
Additional relevant MeSH terms:
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Metabolic Syndrome
Insulin Resistance
Glucose Metabolism Disorders
Metabolic Diseases
Lipid Metabolism Disorders
Nicotinic Acids
Hypoglycemic Agents
Physiological Effects of Drugs
Hypolipidemic Agents
Molecular Mechanisms of Pharmacological Action
Lipid Regulating Agents
Vasodilator Agents
Vitamin B Complex
Growth Substances