A study to investigate the dose of Bilharzia worms that can be safely used to infect humans as a first step to enable testing Bilharzia vaccines

Not Applicable

• Conditions: Schistosomiasis; Infections and Infestations; Schistosomiasis [bilharziasis]

• Registration Number: ISRCTN14033813
• Lead Sponsor: ondon School of Hygiene & Tropical Medicine

Brief Summary

2023 Protocol article in https://pubmed.ncbi.nlm.nih.gov/37538934/ (added 04/08/2023)

Detailed Description

Not available

Study Timeline

• Study Start: 2021-02-01
• Last Update Posted: 22 July 2024
• Study Completion: 2025-12-31

Recruitment & Eligibility

• Status: Ongoing
• Sex: All
• Target Recruitment: 66

Inclusion Criteria

1. Volunteer is aged =18 and =45 years and in good health
2. Volunteer is able to communicate well with the research team members and is available to attend all study visits
3. Volunteer has an adequate understanding of the procedures of the study and agrees to abide strictly thereby
4. Volunteer will remain within Uganda during the study period and is reachable by mobile telephone from until at least week 16 of the study period
5. Volunteer understands the need to avoid contact with waterbodies where Schistosoma is transmitted and can demonstrate that they are able and willing to do so for the full 12-16 week period until the controlled infection has been cured
6. Volunteer agrees to refrain from blood donation throughout the study period
7. For a female volunteer: volunteer agrees to use adequate contraception and not to breastfeed for the duration of the study
8. Volunteer has signed informed consent

Exclusion Criteria

1. Evidence of current Schistosoma infection based on highly sensitive CAA assay (at a conservative cut-off level of >0.5 pg/ml)
2. Evidence of malaria or of intestinal helminth infections (if identified, these will be treated and the volunteer may be reconsidered for inclusion)
3. Any history, or evidence at screening, of clinically significant symptoms, physical signs or abnormal laboratory values suggestive of systemic conditions, such as cardiovascular, pulmonary, renal, hepatic, neurological, dermatological, endocrine, malignant, haematological, infectious, immune-deficient, psychiatric and other disorders, which could compromise the health of the volunteer during the study or interfere with the interpretation of the study results. These include, but are not limited to, any of the following. Note that volunteers may be reconsidered for inclusion following recovery from treatable conditions:
3.1. Temperature =37.5°C/99.5°F
3.2. Body weight <50 kg or Body Mass Index (BMI) <18.0 or >30.0 kg/m² at screening
3.3. Positive HIV, HBV or HCV screening tests
3.4. The use of immune modifying drugs within three months prior to study onset (inhaled and topical corticosteroids and oral anti-histamines exempted) or expected use of such during the study period
3.5. History of malignancy of any organ system (other than localized basal cell carcinoma of the skin), treated or untreated, within the past 5 years
3.6. Any history of treatment for severe psychiatric disease by a psychiatrist in the past year
3.7. History of drug or alcohol abuse interfering with normal social function in the period of 1 year prior to study onset
3.8. Any clinically significant abnormalities (including extended QT interval) on electrocardiogram
4. The chronic use of any drug known to interact with praziquantel, artesunate or lumefantrine metabolism (e.g. phenytoïn, carbamazepine, phenobarbital, primidone, dexamethasone, rifampicin, cimetidine, flecainide, metoprolol, imipramine, amitriptyline, clomipramine, class IA and III antiarrhythmics, antipsychotics, antidepressants, macrolides, fluoroquinolones, imidazole- and triazole antimycotics, antihistamines). Because lumefantrine may cause extension of QT-time, chronic use of drugs with effect on QT interval are excluded from the study
5. For female volunteers: positive urine pregnancy test at screening, or breastfeeding
6. Known hypersensitivity to or contra-indications (including co-medication) for use of praziquantel, artesunate or lumefantrine
7. Participation in another research study involving receipt of an investigational product in the 30 days preceding enrolment, or planned use during the study period
8. Being an employee or student of the Uganda Virus Research Institute or its campus partners, or of Entebbe Hospital
9. Volunteer who, in the opinion of the investigator, does not fully understand the purpose of the study or requirements for participation or is unlikely to adhere to the requirements of the study

Study & Design

• Study Type: Interventional
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
1. Frequency and magnitude of adverse events after controlled human Schistosoma mansoni infection with male cercariae measured using a diary kept by the volunteer and a questionnaire filled out at every visit documenting the participants’ symptoms and signs. These data will be collected at baseline, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 20, 22, 24 and 52 weeks <br>2. Number of male cercariae at which 100% of volunteers show patent infection, i.e. detectable Schistosoma mansoni circulating anodic antigen (CAA), measured using the predefined dose of cercariae administered and a serum CAA assay. A patent infection will be defined as a positive serum CAA test (>1.0 pg/ml) at any time between 0 and 12 weeks following infection with cercariae. CAA will be measured at baseline, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 and 12 weeks