Clinical Trial: Phase I Methodology Study to Validate the Cantharidin Blister Model in Healthy Volunteers

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

Official Title: A Randomised, Single Blind, Placebo-Controlled, Cross-over, Phase 1 Methodology Study to Validate the Cantharidin Blister Model in Healthy Male Volunteers

Brief Summary: The purpose of this study is to refine the cantharidin-induced blister assay in healthy volunteers as a model of inflammatory disease. The study is an experimental trial in healthy volunteers in two parts; Part 1 to optimise the model and Part 2 to validate using two anti-inflammatory treatments with different modes of action.

Detailed Summary: The purpose of this study is to refine the cantharidin-induced blister assay. The cantharidin-induced skin blister assay may be a valuable tool for evaluation of the pharmacodynamic effects of novel anti-inflammatory drugs in healthy volunteers, particularly for novel concepts targeting neutrophilic or monocytic inflammation. The study is an experimental trial in healthy volunteers for the purpose of evaluating the variability (between subjects and within subject) of the size and contents (cellular and fluid) of blisters induced on the forearm by direct application of cantharidin. Specifically, the aim is to assess whether variability is reduced in the current study, in which cantharidin will be applied directly to the skin in order to minimise the variation in total skin exposure. Once experimental design has been optimised then Part 2 of the study will examine the effects of a course of anti-inflammatory treatment prior to induction of blisters on the size and/or contents of blisters in a single blind crossover protocol.
Sponsor: GlaxoSmithKline

Current Primary Outcome:

  • Blister volume of fluid [ Time Frame: 48 hours ]
    Volume of fluid extracted from blisters induced by cantharidin application
  • Cell population in blister fluid [ Time Frame: 48 hours ]
    Flow cytometry performed on cells from blister fluid including measurement of some or all of the following parameters: CD45, CD16, CD14, cell viability, CD206, CD64 or CD84, apoptosis, total blister leukocytes (CD45+), monocytes (CD14+), neutrophils (CD16 high), monocyte/macrophage like cells (CD64+ or CD84+); subsets of these cells that are undergoing apoptosis; subsets of monocyte/macrophages
  • Inflammatory mediators in blister fluid [ Time Frame: 48 hours ]
    Inflammatory mediators in blister fluid, measured by immunoassay as primary endpoints may include (but will not be limited to): MPO, IL-10, IL-8, IL-6, IL-1β, TNF-α, LTB4.


Original Primary Outcome: Same as current

Current Secondary Outcome:

  • Blister volume of fluid [ Time Frame: 72 hours ]
    Volume of fluid extracted from blisters induced by cantharidin application
  • Cell population in blister fluid [ Time Frame: 72 hours ]
    Flow cytometry performed on cells from blister fluid including measurement of some or all of the following parameters: CD45, CD16, CD14, cell viability, CD206, CD64 or CD84, apoptosis, total blister leukocytes (CD45+), monocytes (CD14+), neutrophils (CD16 high), monocyte/macrophage like cells (CD64+ or CD84+); subsets of these cells that are undergoing apoptosis; subsets of monocyte/macrophages
  • Inflammatory mediators in blister fluid [ Time Frame: 72 hours ]
    Inflammatory mediators in blister fluid, measured by immunoassay as primary endpoints may include (but will not be limited to): MPO, IL-10, IL-8, IL-6, IL-1β, TNF-α, LTB4.
  • Numbers and types of leukocytes in blood, and inflammatory mediators in plasma [ Time Frame: 72 hours ]
  • Blister healing/skin appearance at 6 week follow up [ Time Frame: 6 weeks ]


Original Secondary Outcome: Same as current

Information By: GlaxoSmithKline

Dates:
Date Received: November 28, 2012
Date Started: August 2010
Date Completion:
Last Updated: January 7, 2013
Last Verified: January 2013