Clinical Trial: Effect of Zinc Supplementation on Response to Oral Polio Vaccine in Infants in Pakistan

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

Official Title: Effect of Zinc Supplementation on Response to Oral Polio Vaccine in Infants in Pakistan: a Randomized, Controlled Trial

Brief Summary:

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 undernutr

Detailed Summary:

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.

Study population The trial would recruit full term healthy infants of eit
Sponsor: Aga Khan University

Current Primary Outcome: 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. [ Time Frame: From birth to 18 weeks ]

Original Primary Outcome: Same as current

Current Secondary Outcome:

  • Prevalence of excretion of poliovirus serotypes 1, 3 at 0 and 7 days after the administration of bOPV [ Time Frame: 18 and 19 Weeks ]
  • Effect of zinc supplementation on growth of infants [ Time Frame: Day 14 to 18 weeks ]


Original Secondary Outcome: Same as current

Information By: Aga Khan University

Dates:
Date Received: October 25, 2010
Date Started: May 2010
Date Completion:
Last Updated: March 31, 2011
Last Verified: October 2010