Leishmaniasis, CutaneousFLYBITENCT03999970
A Clinical Study to Develop an Uninfected Sand Fly Biting Protocol
A study testing Sand fly bite in people with Leishmaniasis, Cutaneous and Insect Bites, run by University of York at 1 site in United Kingdom.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 65 yearsHealthy volunteers can take part
- Conditions the study is for
- Leishmaniasis, Cutaneous, Insect Bites
- What is being tested?
- Sand fly bite
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 12 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- 3 Oct 2019to 10 Jan 2020
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Healthy adults aged 18 to 65 years on the day of screening
- Willing and able to give written informed consent
- Willing to undergo an Hepatitis B, Hepatitis C \& HIV test
- Willing to undergo a pregnancy test during screening and follow-up visits and must not be breastfeeding (female volunteers)
- Willing to refrain from blood donation during the study
- Using a reliable and effective form of contraception (female volunteers)
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- Judged, in the opinion of a medically qualified Clinical Investigator, to be able and likely to comply with all study requirements as set out in the protocol
- Without any other significant health problems as determined by medical history, physical examination, results of screening tests and the clinical judgment of a medically qualified Clinical Investigator
- Available for the duration of the study
- Willing to refrain from travel to regions where Leishmania-transmitting sand flies are present, from recruitment until the last study visit.
- Willing to consent to a report from the volunteer's GP (General Practitioner) confirming medical eligibility, to be provided before study entry
Who cannot join
- The volunteer may not enter the study if any of the following apply:
- Receipt of a live attenuated vaccine within 30 days or other vaccine within 14 days of screening
- Administration of immunoglobulins and/or any blood products within the three months preceding the planned study.
- History of allergic disease/atopy or reactions or a history of severe or multiple allergies to drugs or pharmaceutical agents
- Any significant chronic skin condition as judged by the medical team
- Any history of Leishmaniasis
Show all 20Show fewer
- Any history of travel within the last 30 days to regions where Leishmania major-transmitting sand flies are endemic*.
- Any past history of more than 30 contiguous days stay in regions where Leishmania major-transmitting sand flies are endemic*.
- Any history of severe local or general reaction to insect bites, defined as
- Local: extensive, indurated redness and swelling involving most of the antero-lateral thigh or the major circumference of the arm, not resolving within 72 hours
- General: fever ≥ 39.5°C within 48 hours, anaphylaxis, bronchospasm, laryngeal oedema, collapse, convulsions or encephalopathy within 48 hours
- Any history of anaphylaxis Females - pregnancy, less than 12 weeks postpartum, lactating or willingness/intention to become pregnant during the study and for 3 months following the study.
- Any clinically significant abnormal finding on screening biochemistry or haematology blood tests or urinalysis
- Total IgE levels >81 Kilo-units/L Any confirmed or suspected immunosuppressive or immunodeficient state, including HIV infection; asplenia; recurrent, severe infections and chronic (more than 14 days) immunosuppressant medication within the past 6 months
- Tuberculosis, leprosy, or malnutrition
- Any chronic illness requiring hospital specialist input
- Any significant psychiatric conditions
- Any other significant disease, disorder or finding, which, in the opinion of a medically qualified Clinical Investigator, may either put the volunteer at risk because of participation in the study, or may influence the result of the study, or the volunteer's ability to participate in the study
- Unlikely to comply with the study protocol
- Involved in current or recent research within the past 3 months (as judged by study investigators) *This refers to regions where Leishmania major-transmitting sand flies are endemic including (but not limited to) the Middle East, Sub-Saharan Africa, and Asia.
Trial locations and contacts
1 site in 1 country.
United Kingdom1 site
Translational Research Facility, Department of Biology, University of York
York, North Yorkshire
About this study
Official title: A Clinical Study to Develop a Sand Fly Biting Protocol Using Pathogen-free Blood-fed Sand Flies
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 particular sand fly is visible but small and inconspicuous. There are different types of leishmaniasis around the world and some can be very serious. They 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 available but many of them are not easy to use or don't work well. Therefore new treatments and vaccines are needed that prevent or work against leishmaniasis.
Read more
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 vital scientific knowledge that has led to advances in the development of drugs and vaccines.
This is an initial study using uninfected (disease-free) sand flies, taking place at the University of York. The information from this study will help us to develop a model in the future using infected sand flies so that the investigators can assess any future vaccines against Leishmaniasis. The investigators will also hold a focus group after the sand fly biting study to explore the experiences of individuals taking part in this study.
Read the detailed description
This is a healthy-volunteer clinical study to develop a sand fly biting protocol. 12 participants will be recruited for the study. It is an open-label randomized clinical study with 2 arms (for 2 different species of sand fly: Phlebotomus papatasi and Phlebotomus duboscqi). Participants will be randomized to each arm with 6 participants in each arm. This study will take place at the Translational Research Facility (Q Block), Hull York Medical School \& Department of Biology, University of York, York.
The participants will be followed up to 21 days post-sand fly bite. There will then be a focus group once all participants have completed their follow-up.
- Conditions
- Leishmaniasis, Cutaneous, Insect Bites
- Being tested
- Sand fly bite
- Keywords
- Cutaneous Leishmaniasis, Controlled Human Infection Model, Sand Fly, Human Challenge
- Medical subject headings
- Leishmaniasis, Cutaneous, Insect Bites and Stings
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Sand fly biteOther
Comparison between sand fly bites from two different species (Phlebotomus papatasi and Phlebotomus duboscqi)
| Study group | Role | What they receive |
|---|---|---|
| Phlebotomus papatasi sand fly bite | Active comparator | Volunteers aged between 18-65 years will receive a bite or bites by sand flies using a watch-like biting chamber placed on the arm. The investigators will initially evaluate the use of biting chambers containing up to 5 sand flies maintained on the arm for 30 minutes, and evaluate the sand fly species Phlebotomus papatasi fed on blood twice in the laboratory prior to human exposure. Receives: Other: Sand fly bite |
| Phlebotomus duboscqi sand fly bite | Active comparator | Volunteers aged between 18-65 years will receive a bite or bites by sand flies using a watch-like biting chamber placed on the arm. The investigators will initially evaluate the use of biting chambers containing up to 5 sand flies maintained on the arm for 30 minutes, and evaluate the sand fly species Phlebotomus duboscqi fed on blood twice in the laboratory prior to human exposure. Receives: Other: Sand fly bite |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percentage of participants who successfully undergo sand fly bite during a 30 minute exposure determined by visual dermatoscopy
Development of a sand fly biting protocol using pathogen-free sand flies which is effective and safe for volunteers:
Volunteers aged between 18-65 years will receive a bite or bites by sand flies using a watch-like biting chamber placed on the arm. The investigators will initially evaluate the use of biting chambers containing up to 5 sand flies maintained on the arm for 30 minutes, and evaluate the two sand fly species Phlebotomus papatasi and Phlebotomus duboscqi fed on blood twice in the laboratory prior to human exposure.
Measured: 21 days
Secondary outcomes (7)
Percentage of participants with visual changes following sand fly bite using photography.
The investigators will use photography to identify and record skin changes following sand fly bite by use of photography.
Measured: 21 days
Percentage of participants with visual changes following sand fly bite using dermatoscopy.
The investigators will use dermatoscopy to identify and record skin changes following sand fly bite.
Measured: 21 days
Percentage of participants with demonstrable serological evidence of sand fly bite. To determine human immunological response to sand fly bite using serology and cellular response measurement.
The investigators will measure serology including Leishmania and sand fly salivary gland antibodies following sand fly bite.
Measured: 21 days
Percentage of participants with demonstrable cellular response evidence of sand fly bite.
The investigators will measure cellular response following sand fly bite
Measured: 21 days
Percentage of participants with demonstrable evidence of change in IgE (immunoglobulin E) following sand fly bite.
The investigators will measure IgE at baseline and following sand fly bite
Measured: 21 days
Percentage of participants with significant change in C-reactive protein following sand fly bite.
C-Reactive protein will be measured at baseline and following sand fly bite/
Measured: 21 days
Determine size of lesion following sand fly bite over time
Rulers will be used to determine the changing size of any lesion
Measured: 21 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Jun 2019
- Study start3 Oct 2019
- Primary completion23 Dec 2019
- Study completion10 Jan 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Leishmaniasis, CutaneousStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Clinical study
- Masking
- None (open label)
- Enrolment
- 12 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of York
- Sponsor type
- University, hospital or other
- Collaborators
- Medical Research Council
- Responsible party
- Principal investigator, Paul Kaye, University of York
- Investigators
- Charles Lacey, BMBS, MD, Principal investigator, University of York
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03999970
- Sponsor's protocol ID
- RE19_030_266151
- Acronym
- FLYBITE
- Status last verified
- Oct 2022
- First submitted
- 23 May 2019
- Last updated
- 31 Oct 2022
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Parkash V, Ashwin H, Sadlova J, Vojtkova B, Jones G, Martin N, Greensted E, Allgar V, Kamhawi S, Valenzuela JG, Layton AM, Jaffe CL, Volf P, Kaye PM, Lacey CJN. A clinical study to optimise a sand fly biting protocol for use in a controlled human infection model of cutaneous leishmaniasis (the FLYBITE study). Wellcome Open Res. 2021 Jun 30;6:168. doi: 10.12688/wellcomeopenres.16870.1. eCollection 2021.
PubMed 34693027Parkash V, Jones G, Martin N, Steigmann M, Greensted E, Kaye P, Layton AM, Lacey CJ. Assessing public perception of a sand fly biting study on the pathway to a controlled human infection model for cutaneous leishmaniasis. Res Involv Engagem. 2021 May 30;7(1):33. doi: 10.1186/s40900-021-00277-y.
PubMed 34053461
Study at a glance
From the registry record, last updated by the sponsor on 31 Oct 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Clinical Study to Develop a Sand Fly Biting Protocol Using Pathogen-free Blood-fed Sand Flies
- ClinicalTrials.gov ID
- NCT03999970
- Acronym / sponsor ID
- FLYBITE / RE19_030_266151
- Conditions
- Leishmaniasis, Cutaneous, Insect Bites
- Keywords
- Cutaneous Leishmaniasis, Controlled Human Infection Model, Sand Fly, Human Challenge
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 12 participants (actual)
- Lead sponsor
- University of YorkUniversity, hospital or other
- Collaborators
- Medical Research Council
- Study start
- 3 Oct 2019 (actual)
- Primary completion
- 23 Dec 2019 (actual)
- Study completion
- 10 Jan 2020 (actual)
- First posted
- 27 Jun 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 particular sand fly is visible but small and inconspicuous. There are different types of leishmaniasis around the world and some can be very serious. They 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 available but many of them are not easy to use or don't work well. Therefore new treatments and vaccines are needed 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 vital scientific knowledge that has led to advances in the development of drugs and vaccines.
This is an initial study using uninfected (disease-free) sand flies, taking place at the University of York. The information from this study will help us to develop a model in the future using infected sand flies so that the investigators can assess any future vaccines against Leishmaniasis. The investigators will also hold a focus group after the sand fly biting study to explore the experiences of individuals taking part in this study.
Detailed description
This is a healthy-volunteer clinical study to develop a sand fly biting protocol. 12 participants will be recruited for the study. It is an open-label randomized clinical study with 2 arms (for 2 different species of sand fly: Phlebotomus papatasi and Phlebotomus duboscqi). Participants will be randomized to each arm with 6 participants in each arm. This study will take place at the Translational Research Facility (Q Block), Hull York Medical School \& Department of Biology, University of York, York.
The participants will be followed up to 21 days post-sand fly bite. There will then be a focus group once all participants have completed their follow-up.
Study design
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- Clinical study
| Arm | Type | Receives |
|---|---|---|
| Phlebotomus papatasi sand fly bite | Active comparator | Other: Sand fly biteVolunteers aged between 18-65 years will receive a bite or bites by sand flies using a watch-like biting chamber placed on the arm. The investigators will initially evaluate the use of biting chambers containing up to 5 sand flies maintained on the arm for 30 minutes, and evaluate the sand fly species Phlebotomus papatasi fed on blood twice in the laboratory prior to human exposure. |
| Phlebotomus duboscqi sand fly bite | Active comparator | Other: Sand fly biteVolunteers aged between 18-65 years will receive a bite or bites by sand flies using a watch-like biting chamber placed on the arm. The investigators will initially evaluate the use of biting chambers containing up to 5 sand flies maintained on the arm for 30 minutes, and evaluate the sand fly species Phlebotomus duboscqi fed on blood twice in the laboratory prior to human exposure. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- Healthy adults aged 18 to 65 years on the day of screening
- Willing and able to give written informed consent
- Willing to undergo an Hepatitis B, Hepatitis C \& HIV test
- Willing to undergo a pregnancy test during screening and follow-up visits and must not be breastfeeding (female volunteers)
- Willing to refrain from blood donation during the study
Key exclusion criteria (20 listed)
- Receipt of a live attenuated vaccine within 30 days or other vaccine within 14 days of screening
- Administration of immunoglobulins and/or any blood products within the three months preceding the planned study.
- History of allergic disease/atopy or reactions or a history of severe or multiple allergies to drugs or pharmaceutical agents
- Any significant chronic skin condition as judged by the medical team
- Any history of Leishmaniasis
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Sand fly biteComparison between sand fly bites from two different species (Phlebotomus papatasi and Phlebotomus duboscqi) | Other | Phlebotomus duboscqi sand fly bite, Phlebotomus papatasi sand fly bite |
Primary outcome
Percentage of participants who successfully undergo sand fly bite during a 30 minute exposure determined by visual dermatoscopy
Time frame: 21 days
Development of a sand fly biting protocol using pathogen-free sand flies which is effective and safe for volunteers: Volunteers aged between 18-65 years will receive a bite or bites by sand flies using a watch-like biting chamber placed on the arm. The investigators will initially evaluate the use of biting chambers containing up to 5 sand flies maintained on the arm for 30 minutes, and evaluate the two sand fly species Phlebotomus papatasi and Phlebotomus duboscqi fed on blood twice in the laboratory prior to human exposure.
7 secondary outcomes
Percentage of participants with visual changes following sand fly bite using photography.
Time frame: 21 days
Percentage of participants with visual changes following sand fly bite using dermatoscopy.
Time frame: 21 days
Percentage of participants with demonstrable serological evidence of sand fly bite. To determine human immunological response to sand fly bite using serology and cellular response measurement.
Time frame: 21 days
Percentage of participants with demonstrable cellular response evidence of sand fly bite.
Time frame: 21 days
Percentage of participants with demonstrable evidence of change in IgE (immunoglobulin E) following sand fly bite.
Time frame: 21 days
Percentage of participants with significant change in C-reactive protein following sand fly bite.
Time frame: 21 days
Determine size of lesion following sand fly bite over time
Time frame: 21 days
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 31 Oct 2022.
- Results publication: PubMed 34693027Parkash V, Ashwin H, Sadlova J, Vojtkova B, Jones G, Martin N, Greensted E, Allgar V, Kamhawi S, Valenzuela JG, Layton AM, Jaffe CL, Volf P, Kaye PM, Lacey CJN. A clinical study to optimise a sand fly biting protocol for use in a controlled human infection model of cutaneous leishmaniasis (the FLYBITE study). Wellcome Open Res. 2021 Jun 30;6:168. doi: 10.12688/wellcomeopenres.16870.1. eCollection 2021.
- Derived from this study: PubMed 34053461Parkash V, Jones G, Martin N, Steigmann M, Greensted E, Kaye P, Layton AM, Lacey CJ. Assessing public perception of a sand fly biting study on the pathway to a controlled human infection model for cutaneous leishmaniasis. Res Involv Engagem. 2021 May 30;7(1):33. doi: 10.1186/s40900-021-00277-y.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Charles Lacey, BMBS, MD principal investigator
University of York
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Sand fly bite in people with Leishmaniasis, Cutaneous and Insect Bites, run by University of York at 1 site in United Kingdom.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 11 inclusion and 20 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 31 Oct 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Percentage of participants who successfully undergo sand fly bite during a 30 minute exposure determined by visual dermatoscopy (time frame: 21 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03999970, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 31 Oct 2022.