Add-on Study of Pentoxifylline in Cutaneous Leishmaniasis
Condition: Cutaneous Leishmaniasis
MeSH terms: Leishmaniasis; Leishmaniasis, Cutaneous
Study type: Interventional
Phase: Phase 2/Phase 3

Summary: 
      The purpose of this study is to determine whether adding pentoxifylline to treatment of
      American cutaneous leishmaniasis with meglumine antimoniate increases the rate and speed of
      clinical response without diminishing safety, and to identify immune correlates of the
      healing response.
    

Detailed description: 
      Failure of first line therapies for cutaneous leishmaniasis is a public health issue. Since
      pathogenesis of dermal leishmaniasis is mediated by the immune and inflammatory responses,
      resolution of disease and control of infection are intimately linked to the host response.
      Several investigations have substantiated "proof of principal" for the therapeutic gain of
      co-adjuvant immunotherapy. This study will evaluate the efficacy and safety of using
      pentoxifylline (PTX) as a co-adjuvant in the treatment of cutaneous leishmaniasis with
      meglumine antimoniate in a randomized, double-blind, controlled trial. One arm will receive
      meglumine antimoniate and PTX and the other arm will receive meglumine antimoniate plus
      placebo. Efficacy will be assessed at the end of the treatment, and 5, 7, 13 and 26 weeks
      after initiation of treatment. Efficacy will be measured as the proportion of patients with
      definitive cure at 26 weeks after initiation of treatment, and time to healing. Safety will
      be assessed at the end of treatment with respect to the frequency and severity of adverse
      events.

      Blood samples will be taken to evaluate the effects of PTX invitro and ex vivo on cells of
      the immune system. Proliferation and secretion of cytokines relevant to the immune and
      inflammatory responses by peripheral blood mononuclear cells will be measured before and
      after treatment. Likewise, macrophages will be differentiated from peripheral blood monocytes
      and infected with a strain of L. panamensis transfected with the luciferase (luc) gene. The
      investigators will measure the capacity of patient macrophages to kill parasites before and
      after treatment using a luminometric assay of viable parasite burden. Additionally, the
      investigators will measure the expression of inducible nitric oxide synthase, an enzyme that
      is necessary for nitric oxide production, one of the main leishmanicidal mechanisms used by
      macrophages. The investigators postulate that the use of the co-adjuvant with antimonials
      will increase the therapeutic response and that indicators predictive of a healing response
      can be identified by this prospective analysis of the immune response and therapeutic
      outcome.
    

Intervention name(s): Meglumine antimonate; Placebo; Pentoxifylline
Intervention type(s): Drug; Drug; Drug
Intervention description(s): Glucantime® 20mg/kg/day IM daily for 20 days; Placebo 400mg orally 3 times a day for 20 days; Pentoxifylline 400mg orally 3 times a day for 20 days
Other intervention name(s): Glucantime ®
Intervention MeSH terms: Meglumine Antimoniate; Pentoxifylline
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary purpose: Treatment
Keywords: Cutaneous Leishmaniasis; pentoxifylline; immunomodulation