Single-sex Female Controlled Human Schistosomiasis Mansoni Infection

NCT04269915 | Completed DMC

• 1 other identifier: CoHSI2
• Study Type: interventional
• Target: 13
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

Schistosomiasis; Schistosomiasis Mansoni

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (5)

• 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

Study Arms (1)

Intervention

EXPERIMENTAL

Volunteers will be exposed to escalating doses of female Schistosoma mansoni cercariae

Biological: female Schistosoma mansoni cercariae

Interventions

female Schistosoma mansoni cercariae BIOLOGICAL

Viable female Schistosoma mansoni cercariae of the Puerto Rican strain

Intervention

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Leiden University Medical Center: lead

Study Sites (1)

Leiden University Medical Center

Leiden, 2333 ZA, Netherlands

Location

Related Publications (1)

• 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.

  PMID: 37837930 BACKGROUND

MeSH Terms

Conditions

Schistosomiasis; Schistosomiasis mansoni

Condition Hierarchy (Ancestors)

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

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: OTHER
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: February 10, 2020
• First Posted: February 17, 2020
• Study Start: August 12, 2020
• Primary Completion: April 14, 2022
• Study Completion: December 12, 2022
• Last Updated: April 19, 2024

Record last verified: 2024-04

Locations

NL (1)