Soil-transmitted Helminth Infections Clinical Trial
— StarwormsWP1Official title:
Validation of Both Automated Quality Assured Egg Counting System and Molecular Markers for Monitoring the Spread of Anthelmintic Resistance.
| Verified date | October 2019 |
| Source | University Ghent |
| Contact | n/a |
| Is FDA regulated | No |
| Health authority | |
| Study type | Interventional |
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.
| Status | Completed |
| Enrollment | 1000 |
| Est. completion date | September 1, 2019 |
| Est. primary completion date | January 1, 2018 |
| Accepts healthy volunteers | Accepts Healthy Volunteers |
| Gender | All |
| Age group | 5 Years to 18 Years |
| Eligibility |
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 |
| Country | Name | City | State |
|---|---|---|---|
| Brazil | Fiocruz - Research institute of Renê Rachou | Belo Horizonte | Minas Gerais |
| Ethiopia | Jimma University | Jimma | |
| Lao People's Democratic Republic | National Institute of Public Health | Vientiane | |
| Tanzania | The Public Health Laboratory - Ivo de Carneri (PHL-IdC) | Chake Chake | Pemba |
| Lead Sponsor | Collaborator |
|---|---|
| University Ghent | Swiss Tropical & Public Health Institute |
Brazil, Ethiopia, Lao People's Democratic Republic, Tanzania,
| Type | Measure | Description | Time frame | Safety issue |
|---|---|---|---|---|
| Primary | Validation of the performance of FECPAKG2 to assess drug efficacy | We will validate the performance of the FECPAKG2 as well as its ability to assess drug efficacy by means of egg reduction rates. | up to 12 months | |
| Primary | In depth evaluation of the FECPAKG2 technique to assess drug efficacy | We will check the variation in egg counts obtained in repeated measurements and by different technicians and make a cost assessment. | up to 12 months | |
| Primary | Validation of b-tubulin gene as a molecular marker for benzimidazole resistance | 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. | up to 24 months | |
| Secondary | Comparing the sensitivity of quantitative PCR with traditional diagnostic tools (Kato-Katz, Mini-FLOTAC and FECPAKG2) for the detection of soil-transmitted helminth infections. | 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. | up to 12 months | |
| Secondary | Comparing the use of individual and pooled stool samples to assess polymorphisms in the ß-tubulin gene. | Pyrosequencing results for ß-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. | up to 24 months |
| Status | Clinical Trial | Phase | |
|---|---|---|---|
| Completed |
NCT04177654 -
Monitoring Drug Efficacy and Anthelmintic Resistance in Soil-transmitted Helminth Programs
|