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

This study has been completed.
Sponsor:
Collaborator:
World Health Organization
Information provided by:
Aga Khan University
ClinicalTrials.gov Identifier:
NCT01229579
First received: October 25, 2010
Last updated: March 31, 2011
Last verified: October 2010
  Purpose

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.


Condition Intervention
Poliomyelitis
Drug: Zinc Sulfate
Drug: Placebo

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Basic Science
Official Title: Effect of Zinc Supplementation on Response to Oral Polio Vaccine in Infants in Pakistan: a Randomized, Controlled Trial

Resource links provided by NLM:


Further study details as provided by Aga Khan University:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Prevalence of excretion of poliovirus serotypes 1, 3 at 0 and 7 days after the administration of bOPV [ Time Frame: 18 and 19 Weeks ] [ Designated as safety issue: No ]
  • Effect of zinc supplementation on growth of infants [ Time Frame: Day 14 to 18 weeks ] [ Designated as safety issue: No ]

Estimated Enrollment: 320
Study Start Date: May 2010
Study Completion Date: January 2011
Primary Completion Date: January 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Zinc Supplement
2.5 ml Zinc supplement syrup daily containing 10 mg of elemental zinc
Drug: Zinc Sulfate
2.5 ml Zinc supplement syrup daily containing 10 mg of elemental zinc from day 14 to 18 weeks of age.
No Intervention: Placebo
2.5 ml supplement syrup daily without elemental zinc
Drug: Placebo
2.5 ml syrup daily with no elemental zinc from day 14 to 18 weeks of age.

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   up to 14 Days
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 0 to 14 days of healthy newborns

Exclusion Criteria:

  • Infants beyond 14 days of age
  • Preterm infants (< 37 weeks gestation or < 2 kg birth weight).
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01229579

Locations
Pakistan
Project Office, Aga Khan University, Matiari
Matiari, Sindh, Pakistan, 71000
Sponsors and Collaborators
Aga Khan University
World Health Organization
  More Information

No publications provided

Responsible Party: Dr Zulfiqar Ahmed Bhutta, Aga Khan University
ClinicalTrials.gov Identifier: NCT01229579     History of Changes
Other Study ID Numbers: 1291-Peds/ERC-09
Study First Received: October 25, 2010
Last Updated: March 31, 2011
Health Authority: Pakistan: AKU ERC

Keywords provided by Aga Khan University:
poliomyelitis
OPV
zinc supplement
diarrhea
placebo
double blind randomized control trial
elemental zinc
seroconversion
bOPV
infants
immunity

Additional relevant MeSH terms:
Poliomyelitis
Myelitis
Central Nervous System Viral Diseases
Virus Diseases
Enterovirus Infections
Picornaviridae Infections
RNA Virus Infections
Central Nervous System Infections
Central Nervous System Diseases
Nervous System Diseases
Spinal Cord Diseases
Neuromuscular Diseases
Zinc
Zinc Sulfate
Trace Elements
Micronutrients
Growth Substances
Physiological Effects of Drugs
Pharmacologic Actions
Astringents
Dermatologic Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on April 14, 2014