Single-sex Controlled Human Schistosomiasis Infection: Safety and Dose Finding

Schistosomiasis Clinical Trial

Official title:

Establishing a Single-sex Controlled Human Schistosomiasis Infection Model: Safety and Dose Finding

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02755324
• Other study ID #: CoHSI1
• Status: Completed
• Phase: N/A
• Start date: October 27, 2016
• Est. completion date: January 21, 2019

Study information

• Verified date: November 2020
• Source: Leiden University Medical Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Groups of 3 or 7 volunteers will be exposed to a predetermined number of male Schistosoma mansoni cercariae until 10 volunteers are found infected.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 17
• Est. completion date: January 21, 2019
• Est. primary completion date: July 19, 2018
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 45 Years

Eligibility

Inclusion Criteria:

1. Subject is aged = 18 and = 45 years and in good health.

2. Subject has adequate understanding of the procedures of the study and agrees to abide strictly thereby.

3. Subject is able to communicate well with the investigator, is available to attend all study visits.

4. Subject will remain within Europe (excluding Corsica) during the study period and is reachable by mobile telephone from week 3 to week 12 of the study period.

5. Subject agrees to refrain from blood donation throughout the study period.

6. For female subjects: subject agrees to use adequate contraception and not to breastfeed for the duration of study.

7. Subject has signed informed consent.

Exclusion Criteria:

1. 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:

• body weight <50 kg or Body Mass Index (BMI) <18.0 or >30.0 kg/m2 at screening;
• positive HIV, hepatitis B or hepatitis C screening tests;
• 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;
• history of malignancy of any organ system (other than localized basal cell carcinoma of the skin), treated or untreated, within the past 5 years;
• any history of treatment for severe psychiatric disease by a psychiatrist in the past year;
• history of drug or alcohol abuse interfering with normal social function in the period of one year prior to study onset.
• Any clinically significant abnormalities (including extended QT interval) on electrocardiogram

2. The chronic use of any drug known to interact with praziquantel, or artesunate or lumefantrine metabolism (e.g. phenytoin, carbamazepine, phenobarbital, primidon, dexamethasone, rifampicin, cimetidine, flecainide, metoprolol, imipramine, amitriptyline, clomipramine, class I and III anti-arrythmics, 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.

3. For female subjects: positive urine pregnancy test at screening.

4. Any history of schistosomiasis or treatment for schistosomiasis.

5. Positive serology for schistosomiasis or elevated serum or urine circulating anodic antigen or positive Schistosoma serology at baseline.

6. Known hypersensitivity to or contra-indications (including co-medication) for use of praziquantel or, artesunate or lumefantrine.

7. Being an employee or student of the department of parasitology or infectious diseases of the Leiden University Medical Center.

Related Conditions & MeSH terms

• Schistosoma Mansoni
• Schistosomiasis

Intervention

Biological:
• male Schistosoma mansoni cercariae
Viable male Schistosoma mansoni cercariae of the Puerto Rican strain

Locations

Country	Name	City	State
Netherlands	Leiden University Medical Center	Leiden

Sponsors (1)

Lead Sponsor	Collaborator
Leiden University

Country where clinical trial is conducted

Netherlands, 

References & Publications (2)

Langenberg MCC, Hoogerwerf MA, Janse JJ, van Lieshout L, Corstjens PLAM, Roestenberg M; CoHSI clinical trial team. Katayama Syndrome Without Schistosoma mansoni Eggs. Ann Intern Med. 2019 May 21;170(10):732-733. doi: 10.7326/L18-0438. Epub 2019 Jan 8. — View Citation

Langenberg MCC, Hoogerwerf MA, Koopman JPR, Janse JJ, Kos-van Oosterhoud J, Feijt C, Jochems SP, de Dood CJ, van Schuijlenburg R, Ozir-Fazalalikhan A, Manurung MD, Sartono E, van der Beek MT, Winkel BMF, Verbeek-Menken PH, Stam KA, van Leeuwen FWB, Meij P — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of grade 3 and 4 adverse events, possibly, probably or definitely related to controlled human Schistosoma mansoni infection with male cercariae.		20 weeks
Primary	The number of male cercariae at which 100% volunteers show detectable Schistosoma mansoni circulating anodic antigen (CAA).		12 weeks
Secondary	Average number of weeks until positive serum circulating anodic antigen test		12 weeks
Secondary	Comparison of the height of the peak serum circulating anodic antigen concentration in low dose compared with high dose group		12 weeks
Secondary	Comparison of the humoral (antibody) response profile by protein and glycan array between infected and uninfected individuals		1 year
Secondary	Differences in in ex vivo lymphocyte profiles between infected and uninfected individuals		1 year