Schistosomiasis Diagnosis Using a CAA Antigen Test (FreebiLyGAB)

July 26, 2021 updated by: Prof. Ayola Akim ADEGNIKA, Centre de Recherche Médicale de Lambaréné

Prospective, Observational Study to Assess the Performance of CAA Measurement as a Diagnostic Tool for the Detection of Schistosoma Haematobium Infections in Pregnant Women and Their Newborn and Child in Lambaréné, Gabon

Schistosomiasis is one of most important human parasitic diseases worldwide. Pregnant women and their infants are two vulnerable population groups, particularly in sub-Saharan Africa, where - amongst other infectious agents - they are heavily exposed to infections with S. haematobium. Adoption of the recommendation and implementation by national disease control programs was however delayed in most African countries, due to the lack of safety data in humans and in the unborn babies. First results from randomized controlled trials with PZQ in pregnant women meanwhile have provided evidence for the safety of PZQ also in newborns.

In Gabon, S. haematobium is the primarily prevalent Schistosoma species infection. As it is true for most of observational and interventional studies on schistosomiasis, the power of the study is weakened due to the low sensitivity of reference schistosomiasis diagnosis applied, and one might correctly assume that a considerable proportion of samples were misclassified as negative in the control groups. Therefore, diagnostic tests that are highly sensitive and specific are essential to the detection of Schistosoma infections and are urgently needed for a test-and-treat strategy to control schistosomiasis in pregnancy as well as tools to determine efficacy of new interventions tested in clinical trials. Circulating anodic antigen (CAA) and circulating cathodic antigen (CCA) have levels correlating with the number of worms and have also been shown to clear within a few days or weeks after successful treatment. Assays measuring serum levels of these antigens (POC-CCA, UCP-LF CAA) are therefore deemed to assess drug efficacy.

Based on above mentioned tools, we decided to assess the accuracy of CAA measurement to determine the Schistosoma infection in two specific conditions: A) as a diagnostic tool for S. haematobium to prepare for the future implementation of a PZQ test-and-treat strategy and B) as a diagnostic tool to measure efficacy of praziquantel in schistosomiasis and pregnancy intervention trials.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

Study design

The freeBILy-GAB study is a set of interlinked prospective, observational studies conducted in Gabon to comprehensively assess the performance of CAA measurement for the detection of S. haematobium infections in pregnant women and infants. The study is composed of 3 sub-studies each targeted to assess a specific objective (see figure 1 for a schematic trial design, procedures and stages). The study activities will also contribute to safety reporting of PZQ use in pregnant women.

Sub-study A: At baseline, a diagnostic study will be conducted that will also allow to select sub-study B study participants. The approach is a prospective, cross-sectional, observational study conducted in pregnant women to determine the sensitivity and specificity of the UCP-LF CAA test for the detection of S. haematobium infections using urine samples. In the absence of a sensitive reference standard test, the index test (UCP-LF CAA) will be compared against a composite diagnostic reference test based on extensive egg microscopy, serology, qPCR on egg DNA, and POC-CCA. Sampling will include standardized urine collection of 3 consecutive days for S. haematobium diagnosis by egg microscopy, UCP-LF CAA testing, qPCR, and POC-CCA, one (1) stool sample (within the 3 days of urine sampling) to control for S. intercalatum and soil-transmitted helminths infections, and 1 blood sample (within the 3 days of urine sampling) to measure anti-Schistosoma antibodies and to detect any other parasitic infections endemic in the region including filarial and Plasmodia spps. and to provide blood cell counts and hemoglobin to assess pregnant women health status. The laboratory staff involved in performing the laboratory assays using the new techniques will be trained prior to the start of the study. Volunteers positive for any parasitic infection except filaria will be treated for the respective parasitic infection (S. haematobium, STH and malaria parasites) following national treatment guidelines. Women positive for S. haematobium by egg microscopy or UCP-LF CAA at baseline will receive either PZQ treatment (1x 40 mg/kg) within 7 days after the third urine sample (early PZQ treatment) or after delivery (late PZQ treatment) following an allocation ratio of 3:1. The late PZQ treatment group serves as a safety control group of PZQ administration to pregnant women and exposure of their offspring (s). Maternal and perinatal safety and efficacy outcomes will be assessed. For efficacy in offspring, birthweight (with low birthweight defined as weight at birth <2.5 kg) and small gestational age (used as an indicator for possible intrauterine growth restriction) will be investigated. In addition, the exposure to PZQ during pregnancy will be evaluated in infants at the age of 12 and 24 months. For efficacy in mothers, maternal anemia (defined as Hb < 11 g/dl) at inclusion and at delivery will be investigated.

Sub-study B is an observational, follow-up study of pregnant women infected with S. haematobium by egg microscopy and/or UCP-LF CAA test and treated with PZQ or intended for late PZQ treatment (see sub-study A). The aim of this sub-study is to assess if the UCP-LF CAA test can be used to evaluate treatment efficacy of PZQ during pregnancy. Women positive for S. haematobium by egg microscopy and/or UCP-LF CAA test and treated with PZQ (see sub-study A) will be actively followed-up. Urine will be collected on day 2, day 4 and day 6 after PZQ treatment to determine the kinetics of CAA decay and then once a week until both egg microscopy as well UCP-LF CAA assay become negative but no longer than 6 weeks after PZQ treatment.

Sub-study C is an observational, longitudinal study on mothers and their newborn babies. This sub-study aims to determine the incidence of S. haematobium infections and age to first S. haematobium infection in life time in infants born from mothers included in the study. Therefore, between 6 and 24 months post-delivery, mother and her infant will be asked to provide urine every three month until UCP-LF CAA test becomes positive for S. haematobium detection. In addition a questionnaire addressing water contact of mother and infant will be applied. If UCP-LF CAA test becomes positive, mothers will be treated with 1x 40 mg/kg PZQ.

Furthermore, outcome of PZQ treatment during pregnancy on infant development will be assessed at the age of 12 and 24 months after delivery in the two groups (early and late PZQ treatment groups). This allows for a comparison to the freeBILy-MAD study in Madagascar.

Study Type

Interventional

Enrollment (Anticipated)

100

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

  • Name: Josiane Y Honkpehedji, MD
  • Phone Number: +24104584616
  • Email: hyjosy@gmail.com

Study Locations

  • Gabon
      • Lambaréné, Gabon
        • Recruiting
        • Centre de Recherches Medicales de Lambarene
        • Contact:
    • Moyen Ogooué
      • Lambaréné, Moyen Ogooué, Gabon, BP 242
        • Not yet recruiting
        • Centre de Recherches Medicales de Lambarene
        • Contact:
        • Contact:
          • Jean C Dejon, MD

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Child
  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Genders Eligible for Study

Female

Description

Inclusion Criteria:

  • Pregnant women with a gestational age comprised between 16 and 30 weeks (based on last date of menses)
  • Willing to deliver in one of the four maternities: three in Lambaréné and one in Fougamou
  • Provide a written informed consent for both themselves and for newborn follow-up or the written informed consent by the legal guardian if pregnant woman is a minor

Exclusion Criteria:

  • - Willing to move out of the study area within the coming 24 months
  • Known having a medically confirmed complicated pregnancy a complicated pregnancy.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Diagnostic
  • Allocation: Randomized
  • Interventional Model: Factorial Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Schistosomiasis treated during pregnancy
Praziquantel 40mg/kg once will be given during pregnancy at second to third trimester
Drug: Praziquantel
Praziquantel to treat schistosomiasis during pregnancy
Other Names:
  • PZQ
Active Comparator: Schistosomiasis treated after pregnancy
Praziquantel 40mg/kg once will be given to parturient after delivery during lactation
Drug: Praziquantel
Praziquantel to treat schistosomiasis during pregnancy
Other Names:
  • PZQ
Experimental: All study participants
UCP-LF CAA and composite diagnostic reference test based on extensive egg microscopy, plus serology, plus qPCR on egg DNA, and plus POC-CC will be used to detect schistosomiasis infection in pregnant women
Diagnostic test: UCP-LF CAA
UCP-LF CAA to diagnose Schistosomiasis during pregnancy
Other Names:
  • CAA
Diagnostic test: composite diagnostic
composite diagnostic reference test based on extensive egg microscopy, serology, qPCR on egg DNA, and POC-CCA to diagnose Schistosomiasis during pregnancy
Other Names:
  • Composite

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
UPC-LF CAA performance
Time Frame: first two years of the study
Test performance of the UCP-LF CAA test for the detection of S. haematobium infection in pregnancy (sub-study A)
first two years of the study
Egg reduction rate
Time Frame: first two years of the study
Egg reduction rate after PZQ treatment (sub-study B)
first two years of the study
CAA reduction rate
Time Frame: first two years of the study
CAA reduction and after PZQ treatment (sub-study B)
first two years of the study
Prevalence of S. hematobium in children using UCP-LF CAA
Time Frame: last two years of the study
Prevalence of S. haematobium infections in infants below two years of age in our study areas as determined by UCP-LF CAA test (sub-study C)
last two years of the study
Prevalence of S. hematobium in children using microscopy
Time Frame: last two years of the study
Prevalence of S. haematobium infections in infants below two years of age in our study areas as determined by egg microscopy
last two years of the study

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Clinical safety assessment upon PZQ intake
Time Frame: anytime after drug administration until the last born child reach two years old.

Adverse events related and or unrelated to PZQ administration to pregnant women will be assessed clinically:

  • During pregnancy
  • At delivery
  • During the first two years of unborn child
anytime after drug administration until the last born child reach two years old.
Efficacy rate using microscopy
Time Frame: first two years of the study
PZQ Cure rate for S. haematobium treatment in pregnancy (sub-study B) assessed by microscopy test
first two years of the study
Efficacy rate using UCP-LF CAA test
Time Frame: first two years of the study
PZQ Cure rate for S. haematobium treatment in pregnancy (sub-study B) assessed by UCP-LF CAA test
first two years of the study

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Centre de Recherche Médicale de Lambaréné

Collaborators

Universität Tübingen

Investigators

  • Principal Investigator: Ayola A ADEGNIKA, MD, PhD, Centre de Recherches Médicales de Lambaréné (CERMEL)
  • Study Chair: Andrea Kreidenweiss, PhD, University Hospital Tuebingen

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

May 1, 2019

Primary Completion (Anticipated)

April 1, 2022

Study Completion (Anticipated)

May 1, 2022

Study Registration Dates

First Submitted

December 8, 2018

First Submitted That Met QC Criteria

December 17, 2018

First Posted (Actual)

December 19, 2018

Study Record Updates

Last Update Posted (Actual)

July 27, 2021

Last Update Submitted That Met QC Criteria

July 26, 2021

Last Verified

July 1, 2021

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • FreebiLyGAB

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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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