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

This study has been completed.
Sponsor:
Collaborators:
World Health Organization
Information provided by (Responsible Party):
Anita Kaniz Mehdi Zaidi, Aga Khan University
ClinicalTrials.gov Identifier:
NCT01695798
First received: September 27, 2012
Last updated: January 14, 2014
Last verified: January 2014
  Purpose

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).


Condition Intervention Phase
Immunity to Polio Vaccines in Malnourished Infants
Immunity to Polio Vaccines in Non-malnourished Infants
Biological: Injectable polio vaccine and Bivalent oral polio vaccine
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Prevention
Official Title: 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.

Resource links provided by NLM:


Further study details as provided by Aga Khan University:

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

  • Compare the effect of IPV on seropositivity between chronically malnourished and normally nourished 9-12 month old infants. [ Time Frame: 12 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]
    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.


Enrollment: 840
Study Start Date: October 2012
Study Completion Date: October 2013
Primary Completion Date: September 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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


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).

  Eligibility

Ages Eligible for Study:   9 Months to 12 Months
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01695798

Locations
Pakistan
Aga Khan University
Karachi, Sindh, Pakistan, 74800
Sponsors and Collaborators
Aga Khan University
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
  More Information

No publications provided

Responsible Party: Anita Kaniz Mehdi Zaidi, Professor, Aga Khan University
ClinicalTrials.gov Identifier: NCT01695798     History of Changes
Other Study ID Numbers: MIPV, ACTRN 12612000259842
Study First Received: September 27, 2012
Last Updated: January 14, 2014
Health Authority: Switzerland:World Health Organization

Keywords provided by Aga Khan University:
poliomyelitis
oral polio vaccine
OPV
seroconversion
mucosal immunity
malnutrition
IPV
Inactivated polio vaccine
Pakistan

Additional relevant MeSH terms:
Poliomyelitis
Malnutrition
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
Nutrition Disorders

ClinicalTrials.gov processed this record on April 17, 2014