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Proposal 681

Title of the Proposed Research

A randomized, double blind, placebo-controlled trial to evaluate the effect of rosiglitazone on metabolic markers in psoriasis patients

Lead Researcher

Alexa B. Kimball

Affiliation

Massachusetts General Hospital
Boston, MA
US

Funding Source

None

Potential Conflicts of Interest

None

Data Sharing Agreement Date

15 August 2014

Lay Summary

Psoriasis is a complex autoimmune inflammatory disease that is associated with hyperproliferation of keratinocytes and elevated levels of numerous inflammatory biomarkers, including cytokines, chemokines, and acute-phase reactants such as fibrinogen and C-reactive protein (CRP) [1]. The psoriasis population has been found to suffer from a higher prevalence of diabetes mellitus [2] and metabolic syndrome [3]. Although the exact pathophysiologic mechanism underlying this association between psoriasis and diabetes and between psoriasis and metabolic syndrome remains unclear, the chronic inflammatory state in psoriasis with the effects of pro-inflammatory cytokines and adipokines may be a significant contributing factor [4]. Rosiglitazone maleate is an anti-diabetic drug in the thiazolidinedione class, which binds and activates peroxisome proliferator-activated receptor gamma (PPAR?), resulting in modulation of insulin sensitivity, inhibition of cytokine production, and promotion of cell differentiation [5]. Previous studies in diabetic patients have shown that although rosiglitazone leads to improved glycemic control, it is also associated with adverse effects on lipid metabolism, including increased total cholesterol, LDL, and triglyceride level [6]. There have been no studies to our knowledge that have analyzed whether these metabolic effects of rosiglitazone hold true within the psoriasis population, whose altered expression of inflammatory mediators and adipokines may affect the impact of rosiglitazone on lipid metabolism.

This study aims to assess the prevalence and incidence of diabetes among psoriasis patients, explore the effect of rosiglitazone on metabolic markers (including fasting plasma glucose, HbA1c, total cholesterol, LDL, and triglyceride level) within psoriasis patients, and examine whether these metabolic effects correlate with the dosage of rosiglitazone. The research will be conducted using the statistical software JMP Pro 11 to perform ANOVA analyses comparing the levels of metabolic markers among patients in the four study arms (2, 4, or 8 mg rosiglitazone or placebo). The prevalence and incidence of diabetes will also be assessed.

References

  • Siegel, D. et al. Inflammation, atherosclerosis, and psoriasis. Clin. Rev. Allergy Immunol 2013.
  • Armstrong, A. W. et al. Psoriasis and the risk of diabetes mellitus: a systematic review and meta-analysis. JAMA Dermatol 2013.
  • Neimann, A. L. et al. Prevalence of cardiovascular risk factors in patients with psoriasis. J. Am. Acad. Dermatol 2006.
  • Gerdes, S. et al. Adipokines and psoriasis. Exp. Dermatol 2011.
  • Kolak, M. et al. Effects of chronic rosiglitazone therapy on gene expression in human adipose tissue in vivo in patients with type 2 diabetes. J. Clin. Endocrinol. Metab 2007.
  • Deeg, M. et al. Pioglitazone versus Rosiglitazone: Effects on Lipids, Lipoproteins, and Apolipoproteins in Head-to-Head Randomized Clinical Studies. PPAR Res 2008.

Study Data Provided

Study 49653/330: A Randomized, Double Blind, Placebo Controlled, Parallel Group Study to Assess the Safety and Efficacy of Three Dose Levels of Rosiglitazone Maleate in the Treatment of Chronic Plaque Psoriasis
Study 49653/331: A Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Study to Assess the Safety and Efficacy of Rosiglitazone Maleate in the Treatment of Chronic Plaque Psoriasis

Statistical Analysis Plan

This will be added after the research is published.

Publication Citation