IPV in Moderate to Severe Chronic Malnourished 9-12 Month Old Children in Karachi. (MIPV)

January 14, 2014 updated by: Anita Kaniz Mehdi Zaidi, Aga Khan University

Immunogenicity of Combined Bivalent OPV and IPV Vaccines at 9 - 12 Months of Age Compared to bOPV Alone in Malnourished and Non-Malnourished Pakistani Infants.

Chronic malnutrition is associated with lack of effective gut immunity which is a possible explanation for why we see polio cases among a proportion of children who have received 7 or more doses of OPV.Our proposed idea is to evaluate if IPV antigen given later in life may act together to boost humoral and mucosal immunity in children belonging to low-income background in Karachi who have moderate to severe chronic malnutrition (height for age Z score less than -2SD). We also intend to compare eIPV + OPV with OPV only in non-malnourished infants at 9 -12 month of age. Thus, the proposed study is a combination of two trials, with study population stratified by nutritional status, each with a reference arm (bOPV) and an experimental arm (bOPV plus IPV).

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

The development of chronic malnutrition is a complex interplay of multiple factors; including genetic predisposition and a whole host of environmental insults. In the urban squatter and peri-urban settlement environments of Karachi where the Aga Khan University (AKU) has established surveillance programs, half of all infants have moderate to severe chronic malnutrition (height for age Z score less than -2 SD) by the time they are 9 -12 months old. IPV has the advantage of parenteral route, thereby bypassing the damaged gut mucosa of malnourished children. It also does not cause the rare vaccine-associated paralysis. Its effectiveness depends on stimulation of serum (blood) neutralizing antibodies that block the spread of poliovirus to the central nervous system. The main disadvantages that have precluded IPV use in low-income countries is high cost, difficulty in adding another injectable vaccine in the EPI schedule at 6, 10, and 14 weeks, and lack of ability to induce a strong mucosal immune response and therefore prevent enteral infection. Additionally, maternal antibodies at this early age neutralize IPV quite effectively. However, as the median age of polio in Pakistan is 15 months for poliovirus type 1 and 18 months for poliovirus type 3, it may be feasible to give a single IPV dose at an older age, avoiding the effects of maternal antibodies and boosting immunity against polio before the majority of these children enter their risk period in Pakistan. Enhanced potency IPV (eIPV) with higher antigen content yields greater than 90% seropositivity against all 3 types after one dose and 100% seropositivity after two doses. Thus using eIPV combined with OPV at 9 - 12 months in moderate to severe chronically malnourished infants may provide improved seroconversion as well as some stimulation of the mucosal immune response. Our proposed idea is to evaluate if IPV antigen given later in life may act together to boost humoral and mucosal immunity in children belonging to low-income background in Karachi who have moderate to severe chronic malnutrition (height for age Z score less than -2SD). We also intend to compare eIPV + OPV with OPV only in non-malnourished infants at 9 -12 month of age. Thus, the proposed study is a combination of two trials, with study population stratified by nutritional status, each with a reference arm (bOPV) and an experimental arm (bOPV plus IPV).

Study Type

Interventional

Enrollment (Actual)

840

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Pakistan
    • Sindh
      • Karachi, Sindh, Pakistan, 74800
        • Aga Khan University

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

9 months to 1 year (CHILD)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Infant aged 9 - 12 months of age
  • Resident of the study area for last 3 month at the time of enrolment
  • Parent/guardian provides informed consent

Exclusion Criteria:

  • Infant already enrolled in any other polio intervention study.
  • Infant found acutely ill at the time of enrolment, requiring emergent medical care
  • Infant with moderate and severe acute malnutrition, defined by a very low weight for height (below -2z and -3z scores of the median WHO growth standards respectively).
  • Refusal of blood testing
  • Receipt of supplementary dose of OPV within 4 weeks of first study visit
  • Infant with certain medical conditions i.e., cerebral palsy, syndromic infants, infants on corticosteroids because of any medical illness, thrombocytopenia (contraindication of intramuscular injections), malignancies and infant with primary immunodeficiency

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: PREVENTION
  • Allocation: RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: NONE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
NO_INTERVENTION: Chronic malnourished bOPV
This arm will receive only bOPV
EXPERIMENTAL: Malnourished IPV+bOPV
This arm will receive IPV and bOPV
Biological: Injectable polio vaccine and Bivalent oral polio vaccine

One dose of IPV given IM (arm, thigh) to infant aged 9-12 month after randomization.

There will be two groups Chronic Malnourished group and Non-Malnourished group. Each group has two arms, which were randomized on IPV+bOPV and bOPOV alone
NO_INTERVENTION: Normally nourished bOPV
This arm will receive only bOPV
EXPERIMENTAL: Normally nourished IPV+bOPV
This arm will receive both IPV and bOPV
Biological: Injectable polio vaccine and Bivalent oral polio vaccine

One dose of IPV given IM (arm, thigh) to infant aged 9-12 month after randomization.

There will be two groups Chronic Malnourished group and Non-Malnourished group. Each group has two arms, which were randomized on IPV+bOPV and bOPOV alone

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Compare the difference in seropositivity and mean geometric titers between baseline sera and post-intervention sera (after 1 month) in chronically malnourished and non-malnourished infants (9-12 month)
Time Frame: 12 months
compare the difference in seropositivity and mean geometric titers between baseline sera and post-intervention sera (after 1 month) in chronically malnourished and non-malnourished infants (9-12 month)receive bivalent OPV compared to single dose of IPV + bOPV
12 months
Compare the effect of IPV on seropositivity between chronically malnourished and normally nourished 9-12 month old infants.
Time Frame: 12 months
12 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Compare mucosal immunity in moderate to severe chronically malnourished and non-malnourished infant who receive bivalent OPV at 9-12 months of age
Time Frame: 12 months
To compare mucosal immunity in moderate to severe chronically malnourished infant who receive bivalent OPV at 9-12 months of age (reference arm) with infant who receive IPV combined with bivalent OPV at 9-12 months of age after a challenge dose of bOPV given one month later.
12 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Aga Khan University

Collaborators

National Institutes of Health (NIH)
World Health Organization

Investigators

  • Principal Investigator: Anita K.M Zaidi, MBBS, SM, Aga Khan University
  • Study Director: Ali F Saleem, MBBS, MCR, FCPS, Aga Khan University
  • Study Director: Farheen Quadri, MBBS, MSCR, Aga Khan University

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

October 1, 2012

Primary Completion (ACTUAL)

September 1, 2013

Study Completion (ACTUAL)

October 1, 2013

Study Registration Dates

First Submitted

September 27, 2012

First Submitted That Met QC Criteria

September 27, 2012

First Posted (ESTIMATE)

September 28, 2012

Study Record Updates

Last Update Posted (ESTIMATE)

January 16, 2014

Last Update Submitted That Met QC Criteria

January 14, 2014

Last Verified

January 1, 2014

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • MIPV
  • ACTRN 12612000259842 (REGISTRY: Australia-New Zealand Trial Registry)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Immunity to Polio Vaccines in Malnourished Infants

Clinical Trials on Injectable polio vaccine and Bivalent oral polio vaccine

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Albania

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

3
Subscribe