Description Module
The Description Module contains narrative descriptions of the clinical trial, including a brief summary and detailed description. These descriptions provide important information about the study's purpose, methodology, and key details in language accessible to both researchers and the general public.
Description Module path is as follows:
Study -> Protocol Section -> Description Module
Description Module
Ignite Creation Date:
2025-12-25 @ 2:02 AM
Ignite Modification Date:
2025-12-25 @ 2:02 AM
NCT ID:
NCT05169060
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.
Detailed Description:
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.
Study:
NCT05169060
Study Brief:
Protocol Section:
NCT05169060