Human Soil Transmitted Helminths (STH) Resistance to Benzimidazole in School Aged Children Living in Gabon

NCT ID: NCT04326868

Last Updated: 2021-08-02

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 255 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-11-11
• Study Completion Date: 2021-01-30

Brief Summary

Soil-transmitted helminths (STHs) infections are common in subtropics and mostly affect the poorest communities, with an impact on human health in many parts of the world. In 2017, World Health organization (WHO) reports more than 1.5 billion people are infected with soil-transmitted helminths worldwide, including 568 million school-age children who need treatment and preventive interventions. Preventive chemotherapy and periodic mass administration with benzimidazoles (BZ) [albendazole (ABZ) and mebendazole (MBZ)] are used to control these parasites. However, rapid reinfection with Ascaris lumbricoides within six months after a completed treatment has been reported, while the reinfection with hookworms is slow. Similarly, the efficacy of these drugs on Trichuris trichiura cure rate is poor. After many years of use of this drug class, there is an increase possibility that BZ resistance could develop. This resistance may occur due to single nucleotide polymorphisms (SNPs) in the β-tubulin gene at positions 167, 198 or 200, as has been reported in animals. Little data exist to show whether any of these polymorphisms do influence the BZ efficacy against STH in humans. The present study will develop methods to look for molecular evidence of BZ drug resistance in human population in order to support the investigation of the control and elimination of neglected tropical diseases (NTDs) in our communities.

Detailed Description

A Randomized Controlled Clinical Trial (RCT) cohort study, to evaluate the efficacy and safety of three benzimidazole derivates drug (Albendazole, Mebendazole, Albendazole Mebendazole, and Albendazole-Pyrantel) to treat major STH in school aged children from Lambaréné and surroundings. After obtaining informed consent from parents or guardians, stool samples will be collected, for infectious status. If positive the participant will be treated with either drug combination. The efficacy and SNP frequencies will be assessed at weeks 3 and 6 post treatment

Description of study population Children of school and preschool age (2 to 17 years old) living in Lambaréné and the surrounding areas are eligible. The choice of school and preschool-aged children is based on the fact that they constitute the main population at risk of infection. In addition, most of the resources available for public health interventions in many endemic areas of soil-transmitted helminths target this group as a cost-effective method for reaching a large part of the population.

The previous analysis of patient cohort reported a success rate of 61% multispecies prevalence amongst children in the study area and considering a significance level of 95% confidence interval (α =5%) and a minimum power of 80%, the investigators will have to include a total of 255 participants in the study

Conditions

Helminths Infection; Drug Resistance

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: SINGLE

Study Groups

Albendazole

ABZ (400mg)

Group Type: ACTIVE_COMPARATOR

Benzimidazole Anthelmintic

Intervention Type: DRUG

The participants diagnosed positive will be randomly assigned to one of the following treatment arms of the study. Parents or guardians of eligible children will be asked to bring them to the CERMEL (clinic). after a brief clinical examination child fulfilling inclusion criteria will be randomly assigned to one of the following treatment regimens of the study.

Albendazole and Mebendazole

ABZ 400mg + 1 tablet of MBZ (500mg)

Group Type: EXPERIMENTAL

Benzimidazole Anthelmintic

Intervention Type: DRUG

The participants diagnosed positive will be randomly assigned to one of the following treatment arms of the study. Parents or guardians of eligible children will be asked to bring them to the CERMEL (clinic). after a brief clinical examination child fulfilling inclusion criteria will be randomly assigned to one of the following treatment regimens of the study.

Albendazole and Pyrantel

ABZ (400mg) + Pyr (125 mg)

Group Type: EXPERIMENTAL

Benzimidazole Anthelmintic

Intervention Type: DRUG

The participants diagnosed positive will be randomly assigned to one of the following treatment arms of the study. Parents or guardians of eligible children will be asked to bring them to the CERMEL (clinic). after a brief clinical examination child fulfilling inclusion criteria will be randomly assigned to one of the following treatment regimens of the study.

Interventions

Benzimidazole Anthelmintic

The participants diagnosed positive will be randomly assigned to one of the following treatment arms of the study. Parents or guardians of eligible children will be asked to bring them to the CERMEL (clinic). after a brief clinical examination child fulfilling inclusion criteria will be randomly assigned to one of the following treatment regimens of the study.

Intervention Type: DRUG

Other Intervention Names

Albendazole; Mebendazole; Pyrantel

Eligibility Criteria

Inclusion Criteria

• Living in Lambaréné and surrounding areas
• Written informed consent or assent
• Microscopy positive for any major Soil-Transmitted helminths

Exclusion Criteria

• Microscopy negative for any STH
• Pregnant women
• Do not be available for followed up.

• Minimum Eligible Age: 2 Years
• Maximum Eligible Age: 17 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Centre de Recherche Médicale de Lambaréné

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Ayôla Akim ADEGNIKA

Role: PRINCIPAL_INVESTIGATOR

Centre de Recherche Médicale de Lambaréné

Locations

Centre de Recherches Médicales de Lammbaréné

Lambaréné, Moyen-Ogooué Province, Gabon

Countries

Gabon

References

Nguema Moure PA, Nzamba Maloum M, Manouana GP, Laclong Lontchi R-A, Mbong Ngwese M, Edoa JR, Frejus Zinsou J, Meulah B, Mahmoudou S, N'noh Dansou EM, Josiane Honkpehedji Y, Romeo Adegbite B, Agnandji ST, Ramharter M, Lell B, Borrmann S, Kremsner PG, Dejon-Agobe JC, Adegnika AA. A randomized assessors-blind clinical trial to evaluate the safety and the efficacy of albendazole alone and in combination with mebendazole or pyrantel for the treatment of Trichuris trichiura infection in school-aged children in Lambarene and surroundings. Antimicrob Agents Chemother. 2024 May 2;68(5):e0121123. doi: 10.1128/aac.01211-23. Epub 2024 Apr 2.

Reference Type: DERIVED

PMID: 38563751 (View on PubMed)

Other Identifiers

CEI- 007/2019

Identifier Type: OTHER

Identifier Source: secondary_id

0084/2019/PR/SG/CNER

Identifier Type: -

Identifier Source: org_study_id