Lovaza® and Microvascular Function in Type 2 Diabetes
Condition: Hypertriglyceridemia; Diabetic Neuropathy
MeSH terms: Diabetic Neuropathies; Hypertriglyceridemia
Study type: Interventional
Phase: Phase 4

Summary: 
      The objective of this study is to determine the efficacy of 6 months of 4 g/day oral Lovaza®
      on endothelial-dependent and heat-induced vasodilation in type 2 diabetics with neuropathy
      and elevated triglyceride levels. Omega-3 fatty acids appear to exert beneficial effects on
      vascular function that are independent of the changes in serum triglycerides. The efficacy
      will be compared with a placebo given at the same duration. Efficacy of the drug will be
      evaluated after 3 and 6 months of treatment. This timeline should be adequate for evaluation
      of the primary neurophysiological endpoints. Previously, the investigators have demonstrated
      that it is feasible to pharmacologically alter nerve fiber density in as little as 18 weeks
      and that this correlates with subjective and objective measures of neurovascular function.
      The investigators are predicting an enhancement of post-ischemic hyperemia of the foot
      dorsum, where the dilative mechanism is primarily endothelium-dependent and a similar
      improvement in heat-induced hyperemia.
    

Detailed description: 
      This pilot study is a within-subject repeated measures design. This study will compare the
      neurophysiological and vascular responses to placebo and treatment with Lovaza® (omega-3-acid
      ethyl esters, Reliant Pharmaceuticals, Inc.) in subjects with type 2 diabetes, neuropathy,
      and dyslipidemia.

      Lovaza's potential mechanism of action is the inhibition of acyl Coenzyme A:1,
      2-diacylglycerol acyltransferase and increased peroxisomal β-oxidation in the liver.

      Subjects will be recruited and a baseline of physiological, neurological and hematological
      profile established for each patient. Forty-four subjects (20 in the active arm, 20 in the
      placebo arm, and 2 replacements for each arm) will receive 4 g/day Lovaza® tablets or placebo
      for a period of 6 months. All subjects will receive a physical and neurological exam as well
      as neurovascular function testing. This includes nerve conduction studies, quantitative
      sensory testing, quantitative autonomic testing, and skin blood flow testing, which includes,
      ischemia reperfusion. Lab tests include an insulin resistance profile, hepatic and renal
      function profiles, lipid profile, C-reactive protein, thyroid stimulating hormone, and fatty
      acids. Other tests include inflammatory markers such as adiponectin and tumor necrosis
      factor-α. The study is powered to detect differences in microvascular function after 6 months
      of Lovaza® and differences in ethnic responses.
    

Intervention name(s): omega-3-ethyl esters; Placebo
Intervention type(s): Drug; Drug
Intervention description(s): Lovaza (TM) (omega-3-ethyl esters) 1 gram Capsules are indicated as an adjunct to diet to reduce very high (>500 mg/dL) triglyceride (TG) levels in adult patients.; Subjects are males or non-pregnant, non-lactating females age 18-80 years. All subjects must have been diagnosed with type 2 diabetes mellitus a minimum of two years according to the current ADA criteria and triglyceride levels above 149 mg/dL. Subjects in this arm will be taking placebo for 6 months.
Other intervention name(s): Lovaza
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary purpose: Treatment