DeBoer Mark Daniel, Platts-Mills James A, Scharf Rebecca J, McDermid Joann M, Wanjuhi Anne W, Gratz Jean, Svensen Erling, Swann Jon R, Donowitz Jeffrey R, Jatosh Samwel, Houpt Eric R, Mduma Estomih
Department of Pediatrics, University of Virginia, Charlottesville, Virginia, USA.
Department of Medicine, University of Virginia, Charlottesville, Virginia, USA.
BMJ Open. 2018 Jul 7;8(7):e021817. doi: 10.1136/bmjopen-2018-021817.
In many developing areas in the world, a high burden of enteric pathogens in early childhood are associated with growth deficits. The tryptophan-kynurenine-niacin pathway has been linked to enteric inflammatory responses to intestinal infections. However, it is not known in these settings whether scheduled antimicrobial intervention to reduce subclinical enteric pathogen carriage or repletion of the tryptophan-kynurenine-niacin pathway improves linear growth and development.
We are conducting a randomised, placebo-controlled, factorial intervention trial in the rural setting of Haydom, Tanzania. We are recruiting 1188 children within the first 14 days of life, who will be randomised in a 2×2 factorial design to administration of antimicrobials (azithromycin and nitazoxanide, randomised together) and nicotinamide. The nicotinamide is administered as a daily oral dose, which for breast-feeding children aged 0-6 months is given to the mother and for children aged 6-18 months is given to the child directly. Azithromycin is given to the child as a single oral dose at months 6, 9, 12 and 15; nitazoxanide is given as a 3-day course at months 12 and 15. Mother/child pairs are followed via monthly in-home visits. The primary outcome is the child's length-for-age Z-score at 18 months. Secondary outcomes for the child include additional anthropometry measures; stool pathogen burden and bacterial microbiome; systemic and enteric inflammation; blood metabolomics, growth factors, inflammation and nutrition; hydrogen breath assessment to estimate small-intestinal bacterial overgrowth and assessment of cognitive development. Secondary outcomes for the mother include breastmilk content of nicotinamide, other vitamins and amino acids; blood measures of tryptophan-kynurenine-niacin pathway and stool pathogens.
This trial has been approved by the Tanzanian National Institute for Medical Research, the Tanzanian FDA and the University of Virginia IRB. Findings will be presented at national and international conferences and published in peer-review journals.
5.0, 4 December 2017.
Haydom Lutheran Hospital, Haydom, Manyara, Tanzania.
NCT03268902; Pre-results.
在世界上许多发展中地区，幼儿肠道病原体的高负担与生长发育迟缓有关。色氨酸-犬尿氨酸-烟酸途径与肠道感染的肠道炎症反应有关。然而，在这些地区，尚不清楚定期进行抗菌干预以减少亚临床肠道病原体携带或补充色氨酸-犬尿氨酸-烟酸途径是否能改善线性生长和发育。
我们正在坦桑尼亚海多姆的农村地区进行一项随机、安慰剂对照、析因干预试验。我们将在出生后的前14天内招募1188名儿童，他们将按照2×2析因设计随机接受抗菌药物（阿奇霉素和硝唑尼特，联合随机分配）和烟酰胺治疗。烟酰胺作为每日口服剂量给药，对于0至6个月的母乳喂养儿童，给母亲服用；对于6至18个月的儿童，直接给儿童服用。阿奇霉素在第6、9、12和15个月时给儿童单次口服；硝唑尼特在第12和15个月时进行为期3天的疗程给药。通过每月的家访对母婴对进行随访。主要结局是18个月时儿童的年龄别身长Z评分。儿童的次要结局包括额外的人体测量指标；粪便病原体负担和细菌微生物组；全身和肠道炎症；血液代谢组学、生长因子、炎症和营养；氢气呼气评估以估计小肠细菌过度生长以及认知发育评估。母亲的次要结局包括母乳中烟酰胺、其他维生素和氨基酸的含量；色氨酸-犬尿氨酸-烟酸途径的血液指标和粪便病原体。
本试验已获得坦桑尼亚国家医学研究所、坦桑尼亚食品药品管理局和弗吉尼亚大学机构审查委员会的批准。研究结果将在国内和国际会议上展示，并发表在同行评审期刊上。
5.0，2017年12月4日。
坦桑尼亚曼雅拉海多姆路德医院。
NCT03268902；预结果。
