Testing Insect Repellents Against Musca Sorbens, the Vector of Trachoma

NCT03813069 | Completed Phase 2 DMC

• 1 other identifier: 2018-kep-132
• Study Type: interventional
• Target: 64
• Locations: 2 countries
• Sites: 2

Brief Summary

Musca sorbens, a fly that feeds from ocular and nasal discharge on humans, is thought to be the vector of trachoma. We are developing methods of fly control that specifically target this species, in the hope of interrupting Ct transmission. To our knowledge, the use of commercially available insect repellents has never been tested for prevention of Musca sorbens fly-eye contact (i.e. nuisance and landing in the peri-ocular area). Given the likely necessity for prolonged and/or high frequency fly-eye contact for Ct transmission, the reduction of these contacts through the use of fly repellents presents an exciting opportunity for disease control. Here we propose a within-subject, non-masked, trial of the use of commercially available insect repellents against Musca sorbens, with two consecutive participant groups in the laboratory and in the field, and a primary endpoint of measuring the protective efficacy of each repellent product. Repellent products will be chosen from: DEET (N,N-diethyl-3-methylbenzamide), IR3535 (3-\[N-butyl-N-acetyl\]-aminopropionic acid ethyl ester), Picaridin (2-(2-hydroxyethyl)-1-piperidinecarboxylic acid 1-methylpropyl ester); PMD (para-Menthane-3,8-diol) or permethrin (m-Phenoxybenzyl)-cis,trans-3-(2,2-dichlorovinyl)-2,2-dimethylcyclopropanecarboxylate). Products tested will be either (1) topical repellents, or (2) in long-lasting, plastic formulations of repellents that can be worn on the body (wearable repellent technologies). The insect repellent synergist Vanillin (4-Hydroxy-3-methoxybenzaldehyde) may be added to the long-lasting plastic formulations, to improve the duration of protection.

Conditions

Trachoma

Outcome Measures

Primary Outcomes (2)

• Protective Efficacy (PE)

  The protection (protective efficacy, p) afforded by a repellent product will be presented as a percentage. p will be estimated by comparing fly-arm contact duration and fly-eye contact frequency, in laboratory and field trials respectively, after application (or wearing) of the repellent product to that during the control period.

  2 months

• Complete Protection Time (CPT)

  Median CPT will be estimated in stage two ('persistence') laboratory trials only, for those repellents that demonstrated more than 30 % PE. The complete protection time for a specific dose will be estimated as the time elapsed until the first fly landing on the arm in each replicate, and based on repeat estimates of CPT, the mCPT will be estimated using a Kaplan-Meier function.

  3 months

Study Arms (5)

Laboratory study

OTHER

Other: IR3535; Other: Permethrin lower dose; Other: Permethrin higher dose

Field study: IR3535

OTHER

Other: IR3535

Field study: Permethrin lower dose

OTHER

Other: Permethrin lower dose

Field study: Permethrin higher dose

OTHER

Other: Permethrin higher dose

Field study: control arm

NO INTERVENTION

Interventions

IR3535 OTHER

The topical repellent IR3535 (3-\[N-butyl-N-acetyl\]-aminopropionic acid ethyl ester) only

Field study: IR3535; Laboratory study

Permethrin lower dose OTHER

A fabric scarf, impregnated with the insecticide permethrin (m-Phenoxybenzyl)-cis,trans-3-(2,2-dichlorovinyl)-2,2-dimethylcyclopropanecarboxylate) that has contact irritancy/spatial repellency. Dose appropriate to children of 10-20 kg.

Field study: Permethrin lower dose; Laboratory study

Permethrin higher dose OTHER

A fabric scarf, impregnated with the insecticide permethrin (m-Phenoxybenzyl)-cis,trans-3-(2,2-dichlorovinyl)-2,2-dimethylcyclopropanecarboxylate) that has contact irritancy/spatial repellency. Dose appropriate to children more than 20 kg.

Field study: Permethrin higher dose; Laboratory study

Eligibility Criteria

• Age: 3 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

Laboratory trial eligibility criteria 1. Participant is aged \> 18 years and \< 65 years and in good health 2. Participant has a good understanding of the procedures of the study and agrees to abide to these procedures 3. Participant is able to communicate well with the investigator, and attend the laboratory for all aspects of the laboratory studies 4. Participant has no known adverse reactions, or evidence at screening of adverse reactions, to the commercially available repellents DEET, PMD, IR3535, Picaridin or Permethrin, or to Vanilla 5. Participant has no known history of skin allergies or hypersensitivity to topical creams 6. Participant agrees to a pre-trial skin reactivity test for all the repellents that will be used in the trial 7. If in the event of the participant experiencing an adverse reaction to a repellent during the trial, the participant agrees to inform his/her general practitioner and seek appropriate treatment if necessary 8. Participant is willing to allow laboratory-reared Musca sorbens flies to land and crawl on their arm, during the modified arm-in-cage assay, for periods of up to ten minutes at a time 9. Participant agrees not to use any perfumed or scented product, including bathing products, for a 24-hour period before each laboratory session 10. Participant has signed informed consent 11. Participant is not a smoker, and will agree to refraining from smoking for the 12 hours before each laboratory trial Field trial eligibility criteria 1. Participant lives in the designated study site 2. Participating households must be within a one-hour drive of Feya General Hospital 3. Participant considers themselves to be in good health, as does the parent or guardian 4. Participant is aged \> 3 years and \< 12 years 5. Participant has a good understanding of the procedures of the study and agrees to abide to these procedures 6. The parent or guardian of the participant has a good understanding of the procedures of the study and agrees to abide to these procedures 7. Participant is able to communicate well with the investigator or fieldworker who is conducting the study 8. Participant has no known adverse reactions to the commercially available repellents DEET, PMD, IR3535, Picaridin or Permethrin, or to Vanilla 9. Participant has no known history of skin allergies or hypersensitivity to topical creams 10. Participant agrees to a pre-trial skin reactivity test for all the repellents that will be used in the trial 11. If in the event of the participant experiencing an adverse reaction to a repellent during the trial, the participant can request medical advice from the Stronger-SAFE field team nurses if they wish 12. Participant is willing to sit still on a chair outside their house, for sequential periods of up to ten minutes, allowing wild fly contact and landing on the body and face, as much as possible without disturbing fly behaviour 13. Participant agrees not to use any perfumed or scented product, including bathing products, for a 24-hour period before each laboratory session 14. Able and willing to give fully informed assent 15. The parent or guardian has signed informed consent

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• London School of Hygiene and Tropical Medicine: lead
• Federal Minstry of Health of Ethiopia: collaborator
• Oromia Regional Health Bureau, Ethiopia: collaborator
• The Fred Hollows Foundation, Ethiopia: collaborator
• The Fred Hollows Foundation, UK: collaborator
• The Fred Hollows Foundation, Australia: collaborator

Study Sites (2)

Fred Hollows Foundation

Addis Ababa, Ethiopia

Location

London School of Hygiene and Tropical Medicine

London, WC1E 7HT, United Kingdom

Location

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MeSH Terms

Conditions

Trachoma

Interventions

ethyl-3-(N-n-butyl-N-acetyl)aminopropionate; Permethrin

Condition Hierarchy (Ancestors)

Conjunctivitis, Bacterial; Eye Infections, Bacterial; Bacterial Infections; Bacterial Infections and Mycoses; Infections; Chlamydia Infections; Chlamydiaceae Infections; Gram-Negative Bacterial Infections; Eye Infections; Conjunctivitis; Conjunctival Diseases; Eye Diseases; Corneal Diseases

Intervention Hierarchy (Ancestors)

Phenyl Ethers; Ethers; Organic Chemicals; Phenols; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Pyrethrins; Cyclopentane Monoterpenes; Monoterpenes; Terpenes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: This is a within-subject, non-masked, trial of the use of commercially available insect repellents against Musca sorbens, with two consecutive participant groups in the laboratory and in the field, and a primary endpoint of measuring the protective efficacy of each repellent product. The first (laboratory-based) study has one arm, in which all participants test all repellent products. Those that are found to generate at least 30 % protective efficacy will be tested in the second (field-based) study, which will have four arms. Up to three arms will test a repellent product and there will be a control arm.

Study Record Dates

• First Submitted: January 7, 2019
• First Posted: January 23, 2019
• Study Start: January 10, 2019
• Primary Completion: December 23, 2019
• Study Completion: December 23, 2019
• Last Updated: April 8, 2020

Record last verified: 2020-04

Data Sharing

• IPD Sharing: Will share

Locations

ET (1); GB (1)