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

• ClinicalTrials.gov Identifier: NCT02755324
• Recruitment Status: Completed
• First Posted: April 28, 2016
• Last Update Posted: November 18, 2020
• Sponsor: Leiden University
• Information provided by (Responsible Party): Meta Roestenberg, Leiden University Medical Center

Study Description

Brief 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.

Condition or disease	Intervention/treatment	Phase
Schistosomiasis; Schistosoma Mansoni	Biological: male Schistosoma mansoni cercariae	Not Applicable

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 17 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Other
• Official Title: Establishing a Single-sex Controlled Human Schistosomiasis Infection Model: Safety and Dose Finding
• Actual Study Start Date: October 27, 2016
• Actual Primary Completion Date: July 19, 2018
• Actual Study Completion Date: January 21, 2019

Arms and Interventions

Arm	Intervention/treatment
Experimental: Intervention; Volunteers will be exposed to escalating doses of male Schistosoma mansoni cercariae	Biological: male Schistosoma mansoni cercariae; Viable male Schistosoma mansoni cercariae of the Puerto Rican strain

Outcome Measures

Primary Outcome Measures :

1. Number of grade 3 and 4 adverse events, possibly, probably or definitely related to controlled human Schistosoma mansoni infection with male cercariae. [ Time Frame: 20 weeks ]
2. The number of male cercariae at which 100% volunteers show detectable Schistosoma mansoni circulating anodic antigen (CAA). [ Time Frame: 12 weeks ]

Secondary Outcome Measures :

1. Average number of weeks until positive serum circulating anodic antigen test [ Time Frame: 12 weeks ]
2. Comparison of the height of the peak serum circulating anodic antigen concentration in low dose compared with high dose group [ Time Frame: 12 weeks ]
3. Comparison of the humoral (antibody) response profile by protein and glycan array between infected and uninfected individuals [ Time Frame: 1 year ]
4. Differences in in ex vivo lymphocyte profiles between infected and uninfected individuals [ Time Frame: 1 year ]

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 45 Years (Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Criteria

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.

Contacts and Locations

Locations

Netherlands

Leiden University Medical Center

Leiden, Netherlands, 2333 ZA

Sponsors and Collaborators

Leiden University

Investigators

• Principal Investigator: Meta Roestenberg; LUMC

More Information

Publications of Results:

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.

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, van Diepen A, van Lieshout L, van Dam GJ, Corstjens PLAM, Hokke CH, Yazdanbakhsh M, Visser LG, Roestenberg M. A controlled human Schistosoma mansoni infection model to advance novel drugs, vaccines and diagnostics. Nat Med. 2020 Mar;26(3):326-332. doi: 10.1038/s41591-020-0759-x. Epub 2020 Feb 17.

• Responsible Party: Meta Roestenberg, MD, PhD, Leiden University Medical Center
• ClinicalTrials.gov Identifier: NCT02755324
• Other Study ID Numbers: CoHSI1
• First Posted: April 28, 2016
• Last Update Posted: November 18, 2020
• Last Verified: November 2020

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Undecided

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Schistosomiasis; Infections; Trematode Infections; Helminthiasis; Parasitic Diseases; Vector Borne Diseases