Lovaza® and Microvascular Function in Type 2 Diabetes
Condition: Hypertriglyceridemia; Diabetic Neuropathy
MeSH terms: Diabetic Neuropathies; Hypertriglyceridemia
Intervention: omega-3-ethyl esters; Placebo
Intervention description: 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.
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Enrollment: 44.0
Sex: All
Minimum age: 18 Years
Maximum age: 80 Years
Healthy volunteers: No

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.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Subjects may be males or non-pregnant, non-lactating females age 18-80 years.

          2. Subjects must have been diagnosed with type 2 diabetes mellitus according to the
             current ADA criteria.

          3. Triglyceride levels above 149 mg/dL

          4. Minimum of 2 years after diagnosis of type 2 diabetes

          5. Prior to participation in this study, each subject must sign an informed consent
             document.

        Exclusion Criteria:

          1. Presence of type 1 diabetes mellitus (defined as C-peptide < 1 ng/ml or diabetes onset
             at < 35 years of age in a non-obese patient).

          2. Presence of diabetic retinopathy that is more severe than "background" level.

          3. Presence of diabetic nephropathy, defined by urine dipstick results greater than 300
             mg/100 mL for protein (proteinuria).

          4. Presence of clinically significant neuropathy that is clearly of non-diabetic origin,
             e.g. alcoholic or autoimmune.

          5. Bilateral amputation of lower extremities or foot ulcers involving the great toes.
             Presence of neuroarthropathy (Charcot deformity) is allowable.

          6. History of major macrovascular events such as myocardial infarction or stroke.

          7. Participation in another clinical trial concurrently or within 30 days prior to entry
             into this study.

          8. The use of ACE-inhibiting agents or angiotensin receptor blockade therapy (ARB) is
             allowed but must have been stable for at least 30 days prior to study entry and may
             not change during the course of the study. This is prudent due to their potential
             effects on blood flow.

          9. Patients with moderate or severe hepatic insufficiency or abnormalities of liver
             function defined as any liver enzymes (aspartate aminotransferase,alanine
             transaminase, alkaline phosphatase) greater than 3 times the upper limit of normal.

         10. Presence of pedal edema.

         11. Presence or history of heart failure New York Heart Association Class II or greater.

         12. Other serious medical conditions that in the opinion of the investigator, would
             compromise the subject's participation in the study.

         13. Concomitant use of medications known to exacerbate triglyceride levels, such as
             estrogens.