Clinical trial NCT02597556: The Impact of Anthelmintic Treatment on the Incidence of Diarrheal Disease in Vietnamese School Children
Official title: A Randomized, Double-blind, Placebo-controlled Trial to Evaluate the Impact of Anthelmintic Treatment on the Incidence of Diarrheal Disease in School Children in Southern Vietnam
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE4
Conditions: Intestinal Helminthiasis
Diarrhea
Keywords: Albendazole
Ancylostoma duodenale
Ascariasis lumbricoides
Coinfection
Diarrhea
Helminths
Necator americanus
Microbiota
Trichuris trichiura
Lead sponsor: Oxford University Clinical Research Unit, Vietnam
Sponsor class: OTHER
Collaborators: name: Hospital for Tropical Diseases, Ho Chi Minh City, Vietnam
name: Ho Chi Minh Preventive Medicine Centre, Vietnam
name: Princeton University
name: Cu Chi Health Department
First posted: 2015-11-05
Enrollment: 0
Sex: ALL
Minimum age (years): 6
Maximum age (years): 15
Standard ages: CHILD
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Cheap and effective drugs called 'anthelmintics' are routinely administered to children in developing countries to eliminate infections by parasitic helminths. However, the effects of anthelmintic treatment on other pathogens (e.g., bacteria, viruses, protozoa) remain unknown. The aim of this study is to investigate the impact of anthelmintic treatment on the incidence of viral- and bacterial-induced diarrhea in school children in southern Vietnam. Diarrheal disease remains a substantial cause of morbidity and mortality in children in Vietnam, and these children are typically co-infected with intestinal helminths. As helminths and diarrheal pathogens infect the same intestinal niche, anthelmintic treatments may alter host immune responses and the composition of the gut microbiota in ways that affect infection and disease risks caused by diarrheal pathogens.

This study will recruit 350 helminth-infected and 350 helminth-uninfected children aged 6-15 years. Recruited children will be randomized to receive either anthelmintic or placebo treatment once every three months and will be monitored for incidences of diarrheal disease for 12 months. At the 12-month time point, all children will receive anthelmintic treatment. Blood and stool samples will be collected throughout the study and used for evaluation of anemia and host immune responses, and for classification of gut microbes and parasite detection, respectively. The interventional study proposed here will provide an important first test of whether anthelmintic treatments have any indirect effects on infections caused by diarrheal pathogens.

Detailed description: This study is a randomized, double-blind, placebo-controlled trial to evaluate the effects of 400 mg albendazole treatment against placebo on the incidence of diarrheal disease caused by viral and bacterial pathogens in school children in southern Vietnam. Children will be enrolled from three primary schools in Cu Chi district in Ho Chi Minh City, Vietnam. Children will be screened for infections by the four most common soil-transmitted helminths, Ascaris lumbricoides, Trichuris trichiura, Necator americanus, and Ancylostoma duodenale. Infected and uninfected individuals will be recruited into the study and randomized to either receive albendazole treatment once every three months for 12 months, or to placebo once every three months for 9 months, after which albendazole treatment will be given at month 12, in accordance with the current deworming schedule in Cu Chi district. A questionnaire regarding the participant's demographics, his/her daily habits, and potential sources of infection will be administered at baseline. Weekly active and passive surveillance of diarrheal cases will be conducted throughout the study, and a health questionnaire will be administered during all cases of diarrhea and at the end of the study.

Eligibility criteria: Inclusion Criteria:

* Between 6-15 years of age
* Written informed consent from a parent or guardian
* Written assent from children \>10 years of age

Exclusion Criteria:

* Subjects who do not fulfill any component of the inclusion criteria
* Subjects that are both hookworm-positive and anemic, as defined by the WHO guidelines

Primary outcomes:
measure: Incidence of diarrheal disease assessed by 12 months of weekly active and passive case surveillance
timeFrame: 12 months
Secondary outcomes:
measure: Prevalence and intensity of soil-transmitted helminth infections by real-time PCR and microscopy
timeFrame: Baseline, 0.5, 3, 6, 6.5, 9, and 12 months, and during and two weeks after diarrhea cases
measure: Prevalence and intensity of enteric viruses and bacteria that cause diarrhea assessed by real-time PCR and the Luminex xTAG Gastrointestinal Pathogen Panel
timeFrame: Time Frame: Baseline, 3, 6, 9, and 12 months, and during and two weeks after diarrhea cases
measure: Changes in fecal microbiota composition by Illumina sequencing
timeFrame: Baseline, 0.5, 3, 6, 6.5, 9, and 12 months, and during and two weeks after diarrhea cases
measure: Changes in blood cytokine (Th1, Th2, TH17, and Treg) levels by bead-based immunoassays
timeFrame: Baseline, 6, and 12 months of study
measure: Antibody isotype response to helminth and diarrheal antigens by ELISA
timeFrame: Baseline, 6, and 12 months
measure: Mean z-scores (height-for-age, weight-for-age, weight-for-height)
timeFrame: Baseline and 12 months
Other outcomes:
Locations:
city: Ho Chi Minh city
country: Vietnam
facility: Cu Chi, Viet Nam
Study officials:
affiliation: Oxford University Clinical Research Unit
name: Stephen Baker, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Pham Ngoc Thach University of Medicine
name: Nghia Ho Dang Trung, PhD, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Princeton University, USA
name: Andrea Graham, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Princeton University, USA
name: Jacqueline Leung, MA
role: STUDY_DIRECTOR
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