Comparison Trial Between Two Repellent Products and a Positive Control Against Culicoides Nubeculosus Midges
Condition: Midge Bites
Study type: Interventional

Summary: 
      Comparison trial between two repellent products and a positive control against Culicoides
      nubeculosus midges. A single-centre laboratory setting study using healthy volunteers to test
      two insect repellent products and a positive control product against Culicoides nubeculosus
      midges. The test products are designed for use by the general public in areas where midge
      biting is likely.
    

Detailed description: 
      Mosquitoes, midges and other biting insects are vectors of extremely important diseases such
      as malaria, yellow fever, filariasis and many viruses and also may be of great nuisance
      value. The use of repellent products can provide added personal protection from disease
      transmission and nuisance bites. New effective repellents would offer an additional option
      for protection against biting insects. The aim of this study is to determine the
      effectiveness of two topically applied insect repellent products provided and one positive
      control against Culicoides nubeculosus. Culicoides nubeculosus is a common species of biting
      midges belonging to the family Ceratopogonidae. Culicoides midges are small biting flies
      found throughout the world, breeding primarily in moist, damp, muddy habitats. To develop
      their eggs, female Culicoides require a blood meal from warm-blooded vertebrates, most often
      a domesticated animal and humans. Culicoides are implicated in the transmission of multiple
      zoonotic diseases, such as bluetongue virus, African horse sickness, and bovine ephemeral
      fever, and their bites can be painful and can cause uncomfortable irritation to both humans
      and livestock.

      This is a single-centre, single-arm study with all participants testing two formulations
      containing PMD and a positive control product containing Picaridin. The control for each test
      is an untreated arm. There is no blinding or randomisation employed, since the outcome
      measures are based on midge behaviour. Repellent product testing takes place in a laboratory
      setting using 7 participants (preferably gender balanced). Each participant will test both
      PMD formulations and a positive control product.

      Volunteers will be consented prior to any screening procedures being undertaken. Volunteers
      who do not meet the criteria for eligibility will be excluded. In order to assess sensitivity
      in those volunteers who claim not to be sensitive to insect bites, volunteers will be given a
      bite test using the midge species used for testing. Participants can stop at any time without
      giving a reason for withdrawing. Data collected to the point of withdrawal will be used in
      the analysis of the study, unless the participant requests that their data is not used, in
      which case it will be removed from the database. Participants may also be removed at the
      discretion of the Chief Investigator, where continued participation may affect the safety of
      the participant or where there is a development of any condition which might interfere with
      study participation.

      All adverse events and serious adverse events should be reported. Any questions concerning
      adverse event reporting should be directed to the chief investigator in the first instance.

      The midges will be obtained from insecticide-susceptible reference strains held at the
      Pirbright Institute (Institute for Animal Health). They will be maintained at 22-24°C, 80-90%
      relative humidity, with a 12:12 hour photoperiod. Female midges will be host-seeking, of
      uniform age and 3-8 days post-emergence. Active host-seeking females will be selected to
      ensure a good response from the test midges using an aspirator or an appropriate airflow
      apparatus. Before the start of each test, the participant will insert a bare (control) left
      arm into the cage for 1 minute to assess biting activity of the midges. Only cages with at
      least 10 midges landing within one minute will be used in the tests. This same procedure is
      used to assess whether volunteers are attractive to the midges. The number of midges probing
      or biting the arm after 1 minute will be counted and recorded (to provide biting rate data of
      the control test for the Protective Efficacy endpoint) and the arm removed from the cage.
      Immediately after, the right (treated) arm is inserted into the cage for 1 minute. The number
      of midges probing or biting the arm after 1 minute will be counted and recorded. A further
      hour post-application of the repellent product, the left arm (control) of the volunteer is
      again inserted into the cage. The number of midges probing or biting the arm after 1 minute
      will be counted and recorded and the arm removed from the cage. If less than 10 midges land
      on the untreated arm during this 1 minute test the cage will be refreshed with new midges and
      the test repeated. Immediately after, the right (treated) arm is again inserted into the cage
      for 1 minute. The number of midges probing or biting the arm after 1 minute will be counted
      and recorded. This procedure will be repeated at hourly intervals throughout the test.

      The products will be applied to the forearm between the wrist and elbow. Volunteers' forearm
      surface area is estimated using the WHO protocol for testing skin repellents below:

      Area=1⁄(2 ) (C_W+C_E ) X D_EW

      Where CW is the circumference of the wrist; CE is the circumference of the elbow; and DEW is
      the distance between the wrist and elbow in centimetres (cm). The dose is expressed using
      µl/cm2. The appropriate dose is then measured using a micropipette or balance and applied to
      the arm using a gloved finger.

      Participants will be followed up within 72 hours after the test to assess any possible side
      effects or reactions to the bites and/or products.

      With the exception of the Volunteer Questionnaire, which is completed by the participant, all
      data collected will be recorded in the case report forms (CRF) and signed by the person
      completing the CRF. The CRF is considered to be source data. Data to be collected are:
      Participant number and date of visit on every page, confirmation of informed consent, date of
      birth, eligibility details, bite test details (midge species, timing, 10 min and 72 h
      assessments), test visits (eligibility checklist, forearm measurement, product details,
      product application details, arm-in-cage testing data (time, fitness check, No. midges
      probing control arm, No. midges probing treated arm)) and adverse event monitoring. Data will
      be double entered and verified to ensure accuracy. CRFs will be kept in locked storage.
      Information in the database for each test will be linked to a relevant SOP, risk assessment,
      contract, and files of statistical analysis and location of report copy.
    

Intervention name(s): p-Menthane,3-8-diol (PMD) Topical Repellent; Picaridin Topical Repellent
Intervention type(s): Other; Other
Intervention description(s): p-Menthane,3-8-diol (PMD) is a recommended active ingredient, which has been evaluated for safe use by the U.S. Environmental Protection Agency (USEPA)1. According to the USEPA laboratory exposure of animals to the active ingredient, PMD, this resulted in no adverse effects except eye irritation. The eye irritation potential of the finished product formulation has not been studied; therefore as a precaution, the products will be handled in the same way as the active ingredient. The researcher and participant must wear eye protection during application of the product and the potential for eye irritation is described in the Participant Information Sheet. . Participants will be excluded if they have a known allergy to any of the product ingredients, or any skin condition, which may affect their reaction to the product.
There isn't a relevant intervention type hence why other is specified. It is to deter mosquitoes landing on the skin of a human.; Icaridin (trade names include Picaridin) is a known mosquito and midge repellent active ingredient. The active ingredient, Picaridin, has been classified as potentially mildly irritating/uncomfortable to the eyes - participants and researcher will wear safety glasses during handling of the products and the participants will be warned about the potential for irritation during the Informed Consent Procedure. Participants will also be excluded if they have a known allergy to any of the product ingredients, or any skin condition which may affect their reaction to the product.
There isn't a relevant intervention type hence why other is specified. It is to deter mosquitoes landing on the skin of a human.
Other intervention name(s): NEO-PART PMD-XLTM (40% PMD) or NEO-PART PMD-XLTM (35% PMD); Smidge (20% Picaridin)
Intervention model: Single Group Assignment
Intervention model description: This was a single-centre, single-arm study with all participants testing one or more products at one dose. The control for each test was an untreated arm. There was no blinding or randomisation employed, since the outcome measures were based on midge behaviour. Repellent product testing took place in a laboratory setting using 15 participants, with a minimum of 3 of either gender per repellent product. Each participant tested at least one single product at one dose.
Masking: None (Open Label)
Primary purpose: Prevention