Study Status: RECRUITING
Recruit Status: RECRUITING
Study Type: INTERVENTIONAL
Official Title: Effects of Fish Oil � Salsalate on the Omega-3 Index and the Circulating Lipodome of Omega-3 Polyunsaturated Fatty Acid Metabolites in Patients With Type 2 Diabetes and Diabetic Neuropathy
Brief Summary: Diabetic peripheral neuropathy (DPN) is the most common chronic complication of diabetes, affecting about 50% of patients with diabetes and leading to severe morbidity, poor quality of life, high mortality, and high health care costs.
Due to the complex structure and anatomy of the peripheral nervous system, DPN presents with a very broad spectrum of clinical symptoms and deficits, including severe pain, sensory deficits, foot ulcers and amputations.
Presently there is no treatment for DPN and even with good blood glucose control DPN develops especially in patients with type 2 diabetes.
There is a need to identify effective interventions for DPN.
Preclinical studies have provided evidence that the combination of fish oil and salsalate is an effective treatment of DPN.
The human subject study to be performed will examine the effect of fish oil with and without salsalate on the blood lipid profile and circulating metabolites of omega-3 polyunsaturated fatty acids (PUFA).
Fish oil is an excellent source for the nutrition dependent omega-3 PUFA, primarily eicosapentaenoic acid (EPA; 20:5) and docosahexaenoic acid (DHA; 22:6).
These fatty acids are the source of anti-inflammatory metabolites known as resolvin, neuroprotectin and maresin.
Preclinical studies have also demonstrated that the metabolites of EPA and DHA are neuroprotective.
Furthermore, when fish oil is combined with salsalate the production of these metabolites is increased in vivo.
Thus, the investigators hypothesize that fish oil and salsalate will be an effective therapy of DPN.
However, prior to doing a formal study of the effect of fish oil + salsalate on DPN there is a need to learn more about what concentration combination will provide the most efficacious effect on the omega-3 index (defined as the sum of EPA and DHA, as a percentage of total fatty acids in red blood cells) and that will safely increase the production of the anti-inflammatory metabolites.
These studies will be performed at two sites the University of Iowa (Dr.
Yorek) and University of Michigan (Dr.
Pop-Busui) by treating human subjects with type 2 diabetes and DPN with either 2g or 4g of fish oil per day (capsules) for 4 months and then adding salsalate 1.5 g or 3g per day (tablets) to the fish oil treatments for an additional 2 months.
At baseline and after treatment with fish oil alone and after treatment with the combination of fish oil and salsalate the omega-3 index and levels of circulating omega-3 PUFA metabolites will be determined as primary endpoints.
Secondary endpoints will include determination of circulatory inflammatory markers and non-invasive measurements for DPN.
The risks to subjects are minimal and are very reasonable in relation to the importance of the knowledge to be gained.