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Validating Egg-based Diagnostics and Molecular Markers for the Spread of Anthelmintic Resistance (StarwormsWP1)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT03465488
Recruitment Status : Completed
First Posted : March 14, 2018
Last Update Posted : October 21, 2019
Swiss Tropical & Public Health Institute
Information provided by (Responsible Party):
Virologie, University Ghent

Brief Summary:

Soil-transmitted helminths (STHs) are a group of parasitic worms that infect millions of children in sub-tropical and tropical countries, resulting in malnutrition, growth stunting, intellectual retardation and cognitive deficits. To control the morbidity due to these worms, school-based deworming programs are implemented, in which anthelminthic drugs are administered to children without prior diagnosis. The continued fight against these worms is aided by the London declaration on neglected tropical diseases, which helps sustain and expand global drug donation program, resulting in an unprecedented growth of deworming programs. However, the high degree of drug pressure makes deworming programs vulnerable to the development of anthelmintic resistance because they only rely on one drug with sometimes suboptimal efficacy and there is no availability of alternative drugs. Moreover, at present, there is no surveillance system to monitor the emergence and spread of anthelmintic resistance. It remains unclear to what extent the efficacy of drugs may have dropped and whether anthelmintic resistance is already present.

This project aims to strengthen the monitoring and surveillance of drug efficacy and anthelmintic resistance in STH programs. As such, it will support deworming programs in their quest to eliminate STHs as a public health problem.

The specific objectives of the first work package are to validate diagnostic tools to monitor drug efficacy and the spread of anthelmintic resistance, and to validate molecular markers for benzimidazole resistance.

This study will be conducted at four different sites (Ethiopia, Tanzania, Lao PDR and Brazil) and will focus on school-aged children (age 5-14). At baseline subjects will be asked to provide a recent stool sample which will be processed using 3 different microscopic techniques (KK, Mini-Flotac and FECPAKG2). All children will be treated with a single-oral dose of albendazole (ALB) 400 mg and 14-21 days after treatment, a second stool sample will be collected from all children to again determine the fecal egg counts. At each sampling, stool is stored in preservative. Stored stool will be shipped to Belgium for DNA extraction and quantitative PCR (qPCR) analysis. A subset of the samples will be analysed by pyrosequencing to evaluate the single nucleotide polymorphisms in the b-tubulin gene. Pooling of the stored samples will also be performed to compare with the values obtained from analysing individual samples.

Condition or disease Intervention/treatment Phase
Soil-transmitted Helminth Infections Drug: Albendazole Pill 400mg (GSK) Not Applicable

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 1000 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Diagnostic
Official Title: Validation of Both Automated Quality Assured Egg Counting System and Molecular Markers for Monitoring the Spread of Anthelmintic Resistance.
Actual Study Start Date : August 15, 2016
Actual Primary Completion Date : January 1, 2018
Actual Study Completion Date : September 1, 2019

Resource links provided by the National Library of Medicine

Drug Information available for: Albendazole

Arm Intervention/treatment
Experimental: Subjects
All participants that meet all inclusion criteria and none of the exclusion criteria will be enrolled in the study and receive a subject identifier (SubjectID). At baseline, all participants will receive a single treatment of albendazole 400mg and their stool will be examined for helminth eggs. Two to three weeks after treatment a follow-up examination of their stool is performed.
Drug: Albendazole Pill 400mg (GSK)
One single dose of 400mg Albendazole is provided at baseline.
Other Name: Albendazole 400mg form GlaxoSmithKline (Batch Nr: 335726)

Primary Outcome Measures :
  1. Validation of the performance of FECPAKG2 to assess drug efficacy [ Time Frame: up to 12 months ]
    We will validate the performance of the FECPAKG2 as well as its ability to assess drug efficacy by means of egg reduction rates.

  2. In depth evaluation of the FECPAKG2 technique to assess drug efficacy [ Time Frame: up to 12 months ]
    We will check the variation in egg counts obtained in repeated measurements and by different technicians and make a cost assessment.

  3. Validation of b-tubulin gene as a molecular marker for benzimidazole resistance [ Time Frame: up to 24 months ]
    This will be done through assessment of the polymorphisms at the b-tubulin gene using a pyrosequencing approach. We will compare results obtained from the 4 different study sites which have a varying MDA history as well as results obtained from responders, poor responders and non-responders within each different site.

Secondary Outcome Measures :
  1. Comparing the sensitivity of quantitative PCR with traditional diagnostic tools (Kato-Katz, Mini-FLOTAC and FECPAKG2) for the detection of soil-transmitted helminth infections. [ Time Frame: up to 12 months ]
    It is commonly accepted that molecular tools are more sensitive to traditional diagnostic tools, however studies comparing qPCR with a wide range of traditional microscopic techniques are scarce. In this project we will evaluate the performance of qPCR in terms of sensitivity to detect infection compared to the results obtained by coprological analysis of samples by Kato-Katz, Mini-FLOTAC and FECPAKG2.

  2. Comparing the use of individual and pooled stool samples to assess polymorphisms in the β-tubulin gene. [ Time Frame: up to 24 months ]
    Pyrosequencing results for β-tubulin gene from individual samples will be compared to those from pooled samples. This will shed a light on whether or not pooling stool samples provides similar information regarding the presence of single nucleotide polymorphisms as when compared to evaluating individual samples. This is important because pooling samples would allow important cuts in both technical and financial resources to process the samples.

Information from the National Library of Medicine

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Ages Eligible for Study:   5 Years to 18 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes

Inclusion Criteria:

  • Subject, male or female, is 5-14 years of age
  • Subject is otherwise in an healthy condition (medical history and physical examination)
  • Parent(s)/guardians of subjects (or their legally-accepted representatives) signed an informed consent document indicating that they understand the purpose of and procedures required for the study and are willing to have their child participate in the study.
  • Subject of ≥6 years has assented (agreed) to participate in the study.
  • Subject of ≥12 has signed an informed consent document indicating that they understand the purpose of and procedures required for the study and are willing to participate in the study.
  • The subject swallowed the entire drug (ALB 400 mg) under supervision
  • Subject provides a stool sample of at least 9 grams

Exclusion Criteria:

  • Subject has active diarrhea (defined as the passage of 3 or more loose or liquid stools per day) at baseline or follow-up
  • Subject has any acute medical condition or is experiencing a severe concurrent medical condition
  • Subject has a known hypersensitivity to benzimidazole drugs
  • Subject has received an anthelminthic treatment within 90 of the start of the treatment.
  • Subject vomited within 4 hours after drug administration
  • Subject is unable to provide a stool sample at follow-up

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03465488

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Fiocruz - Research institute of Renê Rachou
Belo Horizonte, Minas Gerais, Brazil
Jimma University
Jimma, Ethiopia
Lao People's Democratic Republic
National Institute of Public Health
Vientiane, Lao People's Democratic Republic
The Public Health Laboratory - Ivo de Carneri (PHL-IdC)
Chake Chake, Pemba, Tanzania
Sponsors and Collaborators
University Ghent
Swiss Tropical & Public Health Institute
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Principal Investigator: Bruno Levecke, PhD University Ghent
Additional Information:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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Responsible Party: Virologie, Professor, University Ghent
ClinicalTrials.gov Identifier: NCT03465488    
Other Study ID Numbers: OPP1120972
First Posted: March 14, 2018    Key Record Dates
Last Update Posted: October 21, 2019
Last Verified: October 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: De-identified results will be shared online and with collaborating researchers for further extensive analysis.
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Time Frame: A general overview of the project is already published on our project website. The specific study protocol for work-package 1 of the project is currently being submitted for publication. Once final data is collected, De-identified data will be available through the project website as well. No specific time-frame will be applied.
Access Criteria: Free access for all
URL: https://www.starworms.org/tools/overview/starworms-documents

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
Keywords provided by Virologie, University Ghent:
helminth infections
drug resistance
benzimidazole drugs
Additional relevant MeSH terms:
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Parasitic Diseases
Antiparasitic Agents
Anti-Infective Agents
Anticestodal Agents
Antiplatyhelmintic Agents
Antiprotozoal Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents