Single-sex Female Controlled Human Schistosomiasis Mansoni Infection

Establishing a Female-only Controlled Human Schistosoma Mansoni Infection Model: a Safety and Dose Finding Study (CoHSI2)

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

Study Overview

• Status: Completed
• Conditions: Schistosomiasis; Schistosomiasis Mansoni
• Intervention / Treatment: Biological: female Schistosoma mansoni cercariae

• Study Type: Interventional
• Enrollment (Actual): 13
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Netherlands
  • Leiden, Netherlands, 2333 ZA
    • Leiden University Medical Center

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Subject is aged ≥ 18 and ≤ 45 years and in good health.
• Subject has adequate understanding of the procedures of the study and agrees to abide strictly thereby.
• Subject is able to communicate well with the investigator, is available to attend all study visits.
• Subject will remain within Europe (excluding Corsica) during the study period and is reachable by mobile telephone from week 3 to week 8 of the study period.
• Subject agrees to refrain from blood donation to "Sanquin" (blood bank) or for other purposes throughout the study period.
• For female subjects: subject agrees to use adequate contraception and not to breastfeed for the duration of study.
• Subject has signed informed consent.

Exclusion Criteria:

• 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 human immunodeficiency virus (HIV), hepatitis B virus (HBV) or hepatitis C virus (HCV) 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.
  • The chronic use of any drug known to interact with praziquantel, artesunate or lumefantrine metabolism (e.g. phenytoin, carbamazepine, phenobarbital, primidon, dexamethasone, rifampicin, cimetidine, flecainide, metoprolol, imipramine, amitriptyline, clomipramine, class I-A 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.
• For female subjects: positive urine pregnancy test at screening.
• Any history of schistosomiasis or treatment for schistosomiasis.
• Positive serology for schistosomiasis or elevated serum CAA at screening.
• Known hypersensitivity to or contra-indications (including co-medication) for use of praziquantel, artesunate or lumefantrine.
• Being an employee or student of the department of parasitology or infectious diseases of the Leiden University Medical Center.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Intervention; Volunteers will be exposed to escalating doses of female Schistosoma mansoni cercariae	Biological: female Schistosoma mansoni cercariae; Viable female Schistosoma mansoni cercariae of the Puerto Rican strain

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Number and severity of adverse events, possibly, probably or definitely related to controlled human Schistosoma mansoni infection with female cercariae.	20 weeks
Number of female cercariae at which 100% volunteers show detectable Schistosoma mansoni circulating anodic antigen.	8 weeks

Secondary Outcome Measures

Outcome Measure	Time Frame
Average number of weeks until positive serum circulating anodic antigen (CAA) test	8 weeks
Comparison of peak serum circulating anodic antigen (CAA) concentration in different dose groups	8 weeks
Humoral (antibody) response profile by protein and glycan array between infected and uninfected individuals	1 year
Ex vivo lymphocyte profiles using flow cytometry between infected and uninfected individuals	1 year
Changes over time in commensal gut bacteria by looking at the relative abundance of microbiota using 16S rRNA gene amplicon sequencing after controlled human Schistosoma mansoni infection with female cercariae	1 year

Collaborators and Investigators

• Sponsor: Leiden University Medical Center

Publications and helpful links

General Publications

• Koopman JPR, Houlder EL, Janse JJ, Casacuberta-Partal M, Lamers OAC, Sijtsma JC, de Dood C, Hilt ST, Ozir-Fazalalikhan A, Kuiper VP, Roozen GVT, de Bes-Roeleveld LM, Kruize YCM, Wammes LJ, Smits HH, van Lieshout L, van Dam GJ, van Amerongen-Westra IM, Meij P, Corstjens PLAM, Jochems SP, van Diepen A, Yazdanbakhsh M, Hokke CH, Roestenberg M. Safety and infectivity of female cercariae in Schistosoma-naive, healthy participants: a controlled human Schistosoma mansoni infection study. EBioMedicine. 2023 Nov;97:104832. doi: 10.1016/j.ebiom.2023.104832. Epub 2023 Oct 12.

Study record dates

Study Major Dates

• Study Start (Actual): August 12, 2020
• Primary Completion (Actual): April 14, 2022
• Study Completion (Actual): December 12, 2022

Study Registration Dates

• First Submitted: February 10, 2020
• First Submitted That Met QC Criteria: February 13, 2020
• First Posted (Actual): February 17, 2020

Study Record Updates

• Last Update Posted (Estimated): April 19, 2024
• Last Update Submitted That Met QC Criteria: April 18, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Infections; Vector Borne Diseases; Parasitic Diseases; Helminthiasis; Trematode Infections; Schistosomiasis; Schistosomiasis mansoni
• Other Study ID Numbers: CoHSI2

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No