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

Study Status: Withdrawn
Recruit Status: Withdrawn
Study Type: Interventional

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

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 Summary: 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.
Sponsor: Oxford University Clinical Research Unit, Vietnam

Current Primary Outcome: Incidence of diarrheal disease assessed by 12 months of weekly active and passive case surveillance [ Time Frame: 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.


Original Primary Outcome: Same as current

Current Secondary Outcome:

  • Prevalence and intensity of soil-transmitted helminth infections by real-time PCR and microscopy [ Time Frame: 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: 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 [ Time Frame: 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 [ Time Frame: Baseline, 6, and 12 months of study ]
  • Antibody isotype response to helminth and diarrheal antigens by ELISA [ Time Frame: Baseline, 6, and 12 months ]
  • Mean z-scores (height-for-age, weight-for-age, weight-for-height) [ Time Frame: Baseline and 12 months ]


Original Secondary Outcome: Same as current

Information By: Oxford University Clinical Research Unit, Vietnam

Dates:
Date Received: November 3, 2015
Date Started: February 2016
Date Completion:
Last Updated: December 14, 2016
Last Verified: December 2016