Pharmacokinetic and in Vitro Transmission Blocking Activities Study of Primaquine Compare to Methylene Blue in Healthy Volunteer Both G6PD Normal and G6PD Deficiency
Condition: G6PD Normal; G6PD Deficient; Healthy
MeSH terms: Glucosephosphate Dehydrogenase Deficiency
Study type: Interventional
Phase: Phase 1

Summary: 
      The emergence of partial artemisinin resistance in Plasmodium falciparum on the Cambodia-Thai
      border and more recently on the Myanmar-Thai border jeopardizes the renewed global efforts of
      control and elimination of malaria. Containment of this severe threat requires reduction of
      transmission of the resistant phenotype by adding gametocytocidal drugs to the treatment of
      falciparum malaria. Mathematical models also predict that transmission blocking will be
      required if the goal of malaria elimination is to be achieved. The only drug currently
      available with strong gametocytocidal properties against the more mature gametocytes is
      primaquine. However, the oxidative properties of primaquine readily causes acute haemolysis
      in glucose 6 phosphate dehydrogenase (G6PD) deficiency, the degree of which appears to be
      inversely related to G6PD enzyme activity. Because of these safety concerns, primaquine is
      not widely deployed in treatment regimens for falciparum malaria, even in areas with
      documented artemisinin resistance. Methylene blue, which does not exert its action through an
      oxidative mechanism, is a promising alternative as a gametocytocidal adjuvant to artemisinin
      combination therapies (ACTs). Paul Ehrlich discovered methylene blue as the first synthetic
      drug ever to treat malaria. In contrast with primaquine, the thiazine dye methylene blue
      asserts its properties as an oxidizing agent only at very high doses, whereas at
      pharmacologic doses it has reducing agent properties and is for this reason used as a
      medication for the treatment of methemoglobinemia. A recent laboratory study identified
      methylene blue as a potent inhibitor of gametocyte development across all stages, almost
      fully abolishing P. falciparum transmission to mosquitoes at concentrations readily
      achievable in humans. In addition, a recent clinical study in 180 children with uncomplicated
      falciparum malaria in Burkina Faso showed that, compared to artesunate-amodiaquine alone,
      addition of the cheap drug methylene blue to either artesunate or amodiaquine importantly
      reduced gametocyte carrier rates measured at days 3, 7, and 14 of follow-up. This effect was
      seen both in patients with and without P. falciparum gametocytaemia at baseline. The current
      series of studies will investigate further methylene blue as a potential gametocytocidal drug
      in the treatment of uncomplicated falciparum malaria.
    


Intervention name(s): Regimens (Primaquine, Methylene blue)
Intervention type(s): Drug
Intervention description(s): Primaquine 45 mg single dose Or Methylene Blue 600 mg single dose followed by Methylene Blue 600 mg single dose or Primaquine 45 mg single dose.
Intervention MeSH terms: Primaquine; Methylene Blue
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: G6PD; Primaquine; Methylene blue