The main objective of the investigators studies is to find a safe and effective disease modifying treatment for DPN by translating their preclinical findings (introduced above) to human DPN. However, in an initial step, the investigators’ immediate goal is to determine the most effective dosing combination that will raise the omega-3 index to 8-12 % (postulated to be required for a therapeutic effect) and leading to a maximum increase in circulating levels of omega-3 PUFA metabolites. The overall hypothesis is that a tailored supplementation with fish oil will lead to a therapeutic level in the omega-3 index and combining fish oil and salsalate vs. fish oil alone will safely increase the circulating levels of pro-resolving mediators of omega-3 PUFA and reduce markers of inflammation. The investigators will test this hypothesis in a dose finding clinical trial in subjects with type 2 diabetes with DPN. The Specific Aims are:
Specific Aim 1: Determine the optimal dose of fish oil needed to safely increase the omega-3 index to potentially therapeutic levels in subjects with type 2 diabetes and DPN.
Based on the investigator’s preclinical studies, they hypothesize that an omega-3 index of 8 – 12% will be needed for effectiveness in human DPN.
Specific Aim 2: Determine the optimal fish oil and salsalate combination on the profile and concentration of circulating omega-3 PUFA metabolites and changes in inflammatory markers in participants with type 2 diabetes and DPN.
The investigators will utilize state-of-the-art liquid chromatography tandem mass spectrometry (LC-MS/MS) to determine the change in the circulating lipidomic profile of omega-3 PUFA, and antibody-based assays to measure circulating inflammatory markers: C reactive protein, tumor necrosis factor alpha; and interleukins 6 and 10 in response to above combination in human subjects with type 2 diabetes and DPN.
Completing these aims will establish the optimal dose of fish oil-salsalate combination needed to raise the omega-3 index to potentially therapeutic levels in patients with type 2 diabetes and DPN, and their effect on the formation of the pro-resolving metabolites of omega-3 PUFA in circulation in these subjects.
The investigators proposed research will have immediate significant impact by generating the knowledge needed for the design of a phase 2/3 trial in human DPN to determine whether fish oil and salsalate in combination is an effective disease modifying therapy for DPN. The safety profile of fish oil and salsalate are excellent making them an ideal choice for chronic treatment of DPN.
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. By listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.