Omega-3 Fatty Acid Lipidomics in Diabetes Peripheral Neuropathy
Status:
Not yet recruiting
Trial end date:
2026-01-01
Target enrollment:
Participant gender:
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 4 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.