A Clinical Study to Develop a Controlled Human Infection Model Using Leishmania Major-infected Sand Flies
Condition: Leishmaniasis; Cutaneous Leishmaniases; Insect Bites
MeSH terms: Infections; Leishmaniasis; Leishmaniasis, Cutaneous; Insect Bites and Stings
Study type: Interventional

Summary: 
      The disease leishmaniasis mainly occurs in hot and tropical countries, affects millions of
      people and causes around 20,000 deaths across the world every year. Leishmaniasis is caused
      by the Leishmania parasite and is transmitted by sand flies. The parasite is tiny and not
      visible to the naked eye, whereas the sand fly is visible but small and inconspicuous.

      There are different types of leishmaniasis which can affect the skin (cutaneous
      leishmaniasis) or the internal organs of the body (visceral leishmaniasis). Some of the
      milder forms will produce skin problems which will be localised, whilst other forms of
      leishmaniasis will cause widespread skin changes. The skin lesions of cutaneous leishmaniasis
      can be disfiguring if left untreated.

      There are some treatments for leishmaniasis but many of them are not easy to use or don't
      work well. Therefore, new treatments are needed including vaccines that prevent or work
      against leishmaniasis.

      A solution being adopted for other diseases, which the investigators now wish to adopt for
      leishmaniasis is to develop a 'Controlled human infection model' (CHIM). These models involve
      deliberate exposure of individuals to an infection, in order to better understand how the
      disease works and to test potential vaccines and treatments. They have contributed knowledge
      that has led to advances in the development of treatments.

      This is study builds on an our initial successful study, FLYBITE, where uninfected
      (disease-free) sand flies were used to test the safety aspects and ensure that sand flies
      were able to bite human participants in a controlled environment. The investigators observed
      no major adverse effects and it was well tolerated by participants. The investigators
      therefore wish to proceed to a study using sand flies infected with a form of leishmaniasis
      that causes localised skin disease and is treatable, on the pathway to assessing future
      vaccines.
    

Detailed description: 
      This is a clinical study in up to twelve healthy Leishmania-naïve subjects aged between 18
      and 50 years old who develop a confirmed sand fly bite. Initially six subjects will be
      studied and exposed to biting by Phlebotomus duboscqi infected by Leishmania major. An
      adaptive design will be used, that has been pragmatically designed to minimise unnecessary
      exposure of volunteers to Leishmania and maximise the likelihood of developing a reproducible
      Controlled Human Infection Model.

      The primary objective is the development of a controlled human infection model of Leishmania
      major using sand fly transmission which is (a) effective and (b) safe.

      The first six subjects will be exposed to biting by Phlebotomus duboscqi (sand fly species)
      infected by Leishmania major (species of leishmaniasis causing cutaneous, ie skin disease)
      and assess the 'take rate', that is the number of subjects developing parasitologically
      confirmed cutaneous leishmaniasis (PCCL) lesions. If 6/6 subjects develop PCCL lesions no
      further recruitment will take place; if only < 6 subjects develop PCCL lesions, then an
      adaptive design will be followed.

      This study is based on an initial study, entitled FLYBITE (clinicaltrials.gov identifier:
      NCT03999970).

      the FLYBITE study was a clinical study to develop a sand fly biting protocol using
      pathogen-free blood-fed sand flies. Twelve healthy participants were enrolled into the study
      and all 12 participants experienced at least one successful sand fly bite.
    

Intervention name(s): biting by Phlebotomus duboscqi infected with Leishmania major
Intervention type(s): Other
Intervention description(s): The first six subjects will be exposed to biting by Phlebotomus duboscqi infected by Leishmania major and assess the 'take rate', that is the number of subjects developing parasitologically confirmed cutaneous leishmaniasis (PCCL) lesions. If 6/6 subjects develop PCCL lesions no further recruitment will take place; if only < 6 subjects develop PCCL lesions, then an adaptive design will be followed.
Intervention model: Single Group Assignment
Intervention model description: Controlled human infection study, with an adaptive design. The first six subjects will be exposed to biting by Phlebotomus duboscqi infected by Leishmania major and assess the 'take rate', that is the number of subjects developing parasitologically confirmed cutaneous leishmaniasis (PCCL) lesions. If 6/6 subjects develop PCCL lesions no further recruitment will take place; if only < 6 subjects develop PCCL lesions, then an adaptive design will be followed as described elsewhere.
Masking: None (Open Label)
Primary purpose: Other
Keywords: Leishmaniasis; Cutaneous Leishmaniases; Controlled Human Infection Model; Human Challenge; Sand Fly; Phlebotomus