Validating Egg-based Diagnostics and Molecular Markers for the Spread of Anthelmintic Resistance (StarwormsWP1)
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|ClinicalTrials.gov Identifier: NCT03465488|
Recruitment Status : Completed
First Posted : March 14, 2018
Last Update Posted : October 21, 2019
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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|
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||1000 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|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|
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)
- 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.
- 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.
- 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.
- 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.
- 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.
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|Ages Eligible for Study:||5 Years to 18 Years (Child, Adult)|
|Sexes Eligible for Study:||All|
|Accepts Healthy Volunteers:||Yes|
- 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
- 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
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
|Fiocruz - Research institute of Renê Rachou|
|Belo Horizonte, Minas Gerais, Brazil|
|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|
|Principal Investigator:||Bruno Levecke, PhD||University Ghent|
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
|Responsible Party:||Virologie, Professor, University Ghent|
|Other Study ID Numbers:||
|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.|
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|
|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|
Molecular Mechanisms of Pharmacological Action