Pro-Resolving Mediators in Acute Inflammation in Humans
Condition: Inflammation; Skin; Resolution; Blister
MeSH terms: Blister; Dermatitis; Inflammation
Study type: Interventional
Phase: Early Phase 1

Summary: 
      The investigators are undertaking a clinical blister model with or without dietary
      supplementation with omega-3 fatty acids (i.e., Lovaza) to determine the role of specialized
      pro-resolving mediators - endogenous lipids converted from omega-3 fatty acid precursors
      including those in Lovaza - on inflammation parameters and their resolution.
    

Detailed description: 
      The specific aims of this study are based on the hypothesis that in health, natural
      pro-resolving mechanisms, including specialized pro-resolving mediators and cellular
      effectors, are generated to promote the resolution of acute inflammation. The specific aims
      are:

      Aim 1. Map the formation of specialized pro-resolving mediators and their relationship to
      acute tissue inflammation Aim 2. Determine the influence of omega-3 fatty acids on the
      formation and action of pro-resolving mediators during acute inflammation.

      Medical history and clinical information will be obtained from the participant's health
      record for study purposes to be sure that participants meet the appropriate inclusion and
      exclusion criteria. The phlebotomy and topical application of the cantharidin, the imaging
      and clinical assessment and sampling of blister exudates will be performed by Dr. Katherine
      Walker or Dr. Joseph Merola and clinical study team at Brigham and Women's Hospital in the
      Building For Transformative Medicine (3rd floor, 60 Fenwood Road, Boston, MA). The
      biochemical, immunological and histological analyses will be performed in the laboratories of
      Drs. Bruce Levy and Charles Serhan at BWH in the Building For Transformative Medicine (3rd
      floor, 60 Fenwood Road).

      The intervention protocol will involve simultaneous topical application of 12.5 mcl 0.1%
      cantharidin to two sites on the volar surface of one forearm. This dose is known to elicit a
      consistent, safe, localized reaction entailing redness (erythema), mild tenderness and warmth
      at the site, 2-3 cm in diameter. Subsequently, blister exudative fluid will be removed from
      each blister site, one during onset phase of inflammation (24 hrs after cantharidin) and the
      second during resolution phase (72 hrs after cantharidin). The blister exudates will be
      sampled by piercing the roof of the blister with a sterile needle to collect the exudate at
      designated time points. The site is disinfected prior to collection of the blister exudate
      and subsequently protected by a wound dressing after the sample collection step.

      The intervention protocol will be performed twice for each participant, under 2 distinct
      conditions:

        1. without omega-3 fatty acid supplementation

        2. with omega-3 fatty acid supplementation: the participant will take 4 capsules (1gram
           each) of Lovaza daily at 8pm, starting the evening before blister induction and
           continuing until the second blister fluid has been removed.

      This study is a crossover design to evaluate the production of pro-resolving mediators and
      resolution of experimental inflammation with and without additional omega-3 fatty acid
      supplementation, and to allow each subject to serve as an internal control by undergoing
      blister formation in both conditions. In order to reduce the influence of repeated
      cantharidin blister exposures on the outcome measurements, subjects will be randomized to
      start with either the Lovaza arm or the non-supplementation arm of the blister protocol.
    

Intervention name(s): Lovaza; Cantharone; Phlebotomy
Intervention type(s): Drug; Other; Other
Intervention description(s): Lovaza contains ethyl esters of omega-3 fatty acids (EPA and DHA) obtained from the oil of several fish sources.; Cantharone is a clinical blistering agent for topical use to remove warts and molluscum contagiosum. We plan to use the drug to elicit a small skin blister and inflammatory response. This is a well described clinical inflammation research experimental model with multiple publications of its safety and utility in tracking the host inflammatory response.; Subjects will have blood drawn from the antecubital vein for not more than 15mL at each visit.
Other intervention name(s): omega-3 fatty acid ethyl esters
Allocation: Non-Randomized
Intervention model: Crossover Assignment
Intervention model description: Subjects will participate in a total of 6 study visits clustered into two groups of 3 visits (baseline, 24h and 72h after blister induction) for a total of 72 hours duration. The crossover for each group of 3 visits will be separated by at least 1 week.
Masking: None (Open Label)
Primary purpose: Basic Science
Keywords: Specialized pro-resolving mediators