Effect of Zinc Supplementation on Response to Oral Polio Vaccine in Infants in Pakistan: a Randomized, Controlled Trial
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 320
- 试验地点
- 1
- 主要终点
- Seroconversion rates of polio virus (type 1 and type 3), from blood samples collected at the time of recruitment, at 6 weeks and 18 weeks.
研究概览
简要总结
Pakistan is one of the 4 developing countries where cases of poliomyelitis are still being identified. Despite the incessant efforts by WHO and UNICEF, this disease is far from control. There is a need to develop new and innovative strategies to contain the disease and eradicate it from the countries where new cases continue to be identified.
Zinc is an essential component of scores of enzymes in the human body. Recent reports have indicated that this trace element along with other micronutrients enhances the protective functions of immune cells. Moreover, zinc deficiency leads to dysregulation of balanced host responses to infection resulting into decreased antibody production and suppressed immunity. Zinc is also an essential cofactor for thymulin which is known to modulate cytokine release and induce immune cell proliferation. Zinc deficiency is also found to impair an individual's epithelial barrier function, which may further depress the vaccine entry into the mucosal cells.
Role of zinc in the prevention of diarrheal diseases and other infections in children is well documented. However, there are very few reports about its contribution to enhanced immunity by supporting body's natural defense system.
Zinc insufficiency is widespread in socioeconomically deprived children in South Asia and the recent most national nutrition survey (2003) . Moreover, diarrhea is also very common in infants in Pakistan. Such diarrheal episodes can limit entry of attenuated polio virus into the mucosal cells, thereby, leading to inadequate immune response. Association between recent diarrheal history and increased vaccine failure in infants has been shown in a study from Brazil. The recent Lancet Nutrition series has also recommended regular zinc supplementation to address child undernutrition and stunting and underscored the need to treat diarrheal episodes with zinc to expedite recovery. Other recent studies of zinc supplementation in low birth weight infants in South Asia have also shown significant improvement in diarrheal disease burden and mortality.
On the basis of these lines of evidence, it is possible that some of the cases of vaccine failure in this region could be a consequence of compromised immunity and, hence, diminished response to OPV. This could potentially be reversed by addressing such gross undernutrition and micronutrient deficiencies. It can thus be hypothesized that zinc supplementation at community scale would enhance the immune response in infants to OPV.
In order to test this research question, the investigators propose to undertake 12-month randomized controlled trial among a cohort of Pakistani infants of 0-14 days of age. Such a trial would enable us to understand the synergistic role of zinc (if any) with OPV in enhancing immune response against polio and sero-conversion rates.
详细描述
The investigators propose to carry out a randomized controlled clinical trial in Pakistan to assess the efficacy of zinc supplementation in the first 18 weeks of life on seroconversion due to OPV.
Infants of 0-14 days of age will be recruited and randomized into 2 groups; all the groups would receive the respective OPV doses according to the EPI schedule, and the intervention group, in addition, would receive 10 mg of elemental zinc on a daily basis, for 18 weeks, starting at the age of 14 days.
At 18 weeks (after the 4 weeks of last OPV), the investigators provide an additional dose of bOPV as a challenge and collect stool samples to at 0 and 7 days after delivery at of the bOPV.
Study settings The rural settlement of Hala (population ~ 200,000), located about 200 km north-east of Karachi, Pakistan would be the selected study site, as a high proportion of at-risk under 5 children reside in the area. The large proportion of this population falls in the lower socioeconomic group, according to a recently conducted census in 2008, making the site eminently suitable to test out the trial hypotheses.
The Department of Pediatrics & Child Health, AKU has established liaison with the community members and local government stakeholders, with its research office located in a district-level tertiary care hospital. The nearby vaccination center would assist in delivering the OPV doses, according to the EPI schedule, along with other EPI vaccines. The tertiary health care center (Taluka Hospital, Hala) would provide a place for evaluation and treatment for any unforeseen adverse reactions / events, free of cost.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Basic Science
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 1 Day 至 14 Days（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •0 to 14 days of healthy newborns
排除标准
- •Infants beyond 14 days of age
- •Preterm infants (< 37 weeks gestation or < 2 kg birth weight).
研究组 & 干预措施
Zinc Supplement
2.5 ml Zinc supplement syrup daily containing 10 mg of elemental zinc
干预措施: Zinc Sulfate (Drug)
Placebo
2.5 ml supplement syrup daily without elemental zinc
干预措施: Placebo (Other)
结局指标
主要结局
Seroconversion rates of polio virus (type 1 and type 3), from blood samples collected at the time of recruitment, at 6 weeks and 18 weeks.
时间窗: From birth to 18 weeks
次要结局
- Effect of zinc supplementation on growth of infants(Day 14 to 18 weeks)
- Prevalence of excretion of poliovirus serotypes 1, 3 at 0 and 7 days after the administration of bOPV(18 and 19 Weeks)
研究者
Dr Zulfiqar Ahmed Bhutta
Founding Director, Centre of Excellence in Women and Child Health
Aga Khan University