Role of Insulin Action in Psoriasis Pathogenesis

Psoriasis Clinical Trial

Official title: Role of Insulin Action in Psoriasis Pathogenesis

Status Recruiting

Clinical Trial Summary

The goal of this study is to collect more information from people with plaque psoriasis and to determine if insulin plays a role in the pathogenesis of psoriasis. The main question it aims to answer is if insulin action is preserved or even enhanced in psoriatic lesions despite insulin resistance elsewhere. Participants with plaque psoriasis will have punch biopsies taken of lesional and non-lesional skin after an overnight fast and then during an oral glucose tolerance test. Biopsy specimens will then be assessed for markers of insulin action.

Clinical Trial Description

Psoriasis exhibits a clear and robust epidemiologic association with type 2 diabetes mellitus (T2DM). Although T2DM may exacerbate psoriasis and/or complicate its treatment, we do not understand the mechanisms connecting them. As a starting point, psoriasis appears to worsen the insulin resistance (IR) that underlies T2DM. The study investigators hypothesize that the hyperinsulinemia that attempts to compensate for IR retains the ability to drive proliferation of psoriatic lesions. This would set up a vicious cycle in which psoriasis worsens IR, which in turn stimulates insulin hypersecretion that further intensifies psoriasis. In order to test this hypothesis, the investigators must first determine if insulin signaling in psoriatic lesions is actually hyperactive. The investigators therefore propose in this pilot study to elucidate the nature of insulin signaling in psoriasis by measuring phosphorylation of AKT, insulin's key intracellular signaling mediator, in skin biopsies. We will perform shave punch biopsies of lesional and non-lesional skin in overnight-fasted patients with psoriasis who are overweight or obese and therefore at risk of IR. Another set of biopsies will be taken during an oral glucose tolerance test that stimulates endogenous insulin secretion. The investigators expect that AKT phosphorylation will be attenuated in non-lesional skin of patients determined to have IR compared to those who are Insulin Sensitive (IS) or Insulin Intermediate (II), but that AKT phosphorylation will be preserved or even enhanced in lesional skin despite IR. Determining that insulin action is excessive in psoriatic lesions would suggest reducing insulin levels as a novel psoriasis treatment strategy that would also help to spare patients from difficult immunomodulatory treatments. ;

Related Conditions & MeSH terms

• Insulin Resistance
• Overweight
• Overweight and Obesity
• Plaque Psoriasis
• PreDiabetes
• Psoriasis

• NCT number: NCT06242847
• Study type: Observational
• Source: Columbia University
• Contact: Zachary Sone
• Phone: 2123059336
• Email: zds2120@cumc.columbia.edu
• Status: Recruiting
• Start date: February 2, 2024
• Completion date: May 2025