The Impact of Anthelmintic Treatment on the Incidence of Diarrheal Disease in Vietnamese School Children

Sponsor

Oxford University Clinical Research Unit, Vietnam (Other)

Overall Status

Withdrawn

CT.gov ID

NCT02597556

Collaborator

Hospital for Tropical Diseases, Ho Chi Minh City, Vietnam (Other), Ho Chi Minh Preventive Medicine Centre, Vietnam (Other), Princeton University (Other), Cu Chi Health Department (Other)

Enrollment

Location

Arms

Duration (Months)

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Intestinal Helminthiasis Diarrhea	Drug: Albendazole Drug: Placebo	Phase 4

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

0 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

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 Start Date :

Feb 1, 2016

Actual Primary Completion Date :

May 1, 2016

Actual Study Completion Date :

May 1, 2016

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Albendazole Albendazole will be administered as a single 400mg chewable tablet at 0, 3, 6, 9, and 12 months.	Drug: Albendazole A single 400mg dose of Albendazole administered at 0, 3, 6, 9, and 12 months.
Placebo Comparator: Placebo Matching Placebo will be administered as a single chewable tablet at 0, 3, 6, and 9 months. At month 12, all participants will receive a single 400mg Albendazole tablet.	Drug: Placebo Matching placebo tablet administered at 0, 3, 6, and 9 months. At month 12, all participants will receive a single dose of 400mg Albendazole.

Arm

Intervention/Treatment

Active Comparator: Albendazole

Albendazole will be administered as a single 400mg chewable tablet at 0, 3, 6, 9, and 12 months.

Drug: Albendazole

A single 400mg dose of Albendazole administered at 0, 3, 6, 9, and 12 months.

Placebo Comparator: Placebo

Matching Placebo will be administered as a single chewable tablet at 0, 3, 6, and 9 months. At month 12, all participants will receive a single 400mg Albendazole tablet.

Drug: Placebo

Matching placebo tablet administered at 0, 3, 6, and 9 months. At month 12, all participants will receive a single dose of 400mg Albendazole.

Outcome Measures

Primary Outcome Measures

Incidence of diarrheal disease assessed by 12 months of weekly active and passive case surveillance [12 months]
Incidence of diarrhea will be defined according to WHO guidelines as three or more loose stools in a 24-hour period or at least one bloody/mucoid stool. To be considered a new episode of diarrhea, at least three intervening days of normal stools without other gastrointestinal symptoms need to have passed between diarrhea occurrences.

Secondary Outcome Measures

Prevalence and intensity of soil-transmitted helminth infections by real-time PCR and microscopy [Baseline, 0.5, 3, 6, 6.5, 9, and 12 months, and during and two weeks after diarrhea cases]
Prevalence and intensity of enteric viruses and bacteria that cause diarrhea assessed by real-time PCR and the Luminex xTAG Gastrointestinal Pathogen Panel [Time Frame: Baseline, 3, 6, 9, and 12 months, and during and two weeks after diarrhea cases]
Changes in fecal microbiota composition by Illumina sequencing [Baseline, 0.5, 3, 6, 6.5, 9, and 12 months, and during and two weeks after diarrhea cases]
Changes in blood cytokine (Th1, Th2, TH17, and Treg) levels by bead-based immunoassays [Baseline, 6, and 12 months of study]
Antibody isotype response to helminth and diarrheal antigens by ELISA [Baseline, 6, and 12 months]
Mean z-scores (height-for-age, weight-for-age, weight-for-height) [Baseline and 12 months]

Eligibility Criteria

Criteria

Ages Eligible for Study:

6 Years to 15 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Cu Chi, Viet Nam	Ho Chi Minh city		Vietnam	700000

Sponsors and Collaborators

Oxford University Clinical Research Unit, Vietnam
Hospital for Tropical Diseases, Ho Chi Minh City, Vietnam
Ho Chi Minh Preventive Medicine Centre, Vietnam
Princeton University
Cu Chi Health Department

Investigators

Principal Investigator: Stephen Baker, PhD, Oxford University Clinical Research Unit
Principal Investigator: Nghia Ho Dang Trung, PhD, MD, Pham Ngoc Thach University of Medicine
Principal Investigator: Andrea Graham, PhD, Princeton University, USA
Study Director: Jacqueline Leung, MA, Princeton University, USA