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

NCT ID: NCT01695798

Last Updated: 2014-01-16

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 840 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-10-31
• Study Completion Date: 2013-10-31

Brief Summary

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).

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).

Conditions

Immunity to Polio Vaccines in Malnourished Infants; Immunity to Polio Vaccines in Non-malnourished Infants

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: NONE

Study Groups

Chronic malnourished bOPV

This arm will receive only bOPV

Group Type: NO_INTERVENTION

No interventions assigned to this group

Malnourished IPV+bOPV

This arm will receive IPV and bOPV

Group Type: EXPERIMENTAL

Injectable polio vaccine and Bivalent oral polio vaccine

Intervention Type: BIOLOGICAL

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

Normally nourished bOPV

This arm will receive only bOPV

Group Type: NO_INTERVENTION

No interventions assigned to this group

Normally nourished IPV+bOPV

This arm will receive both IPV and bOPV

Group Type: EXPERIMENTAL

Injectable polio vaccine and Bivalent oral polio vaccine

Intervention Type: BIOLOGICAL

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

Interventions

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

Intervention Type: BIOLOGICAL

Eligibility 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

• Minimum Eligible Age: 9 Months
• Maximum Eligible Age: 12 Months
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

World Health Organization

OTHER

Sponsor Role: collaborator

National Institutes of Health (NIH)

NIH

Sponsor Role: collaborator

Aga Khan University

OTHER

Sponsor Role: lead

Responsible Party

Anita Kaniz Mehdi Zaidi

Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Anita K.M Zaidi, MBBS, SM

Role: PRINCIPAL_INVESTIGATOR

Aga Khan University

Ali F Saleem, MBBS, MCR, FCPS

Role: STUDY_DIRECTOR

Aga Khan University

Farheen Quadri, MBBS, MSCR

Role: STUDY_DIRECTOR

Aga Khan University

Locations

Aga Khan University

Karachi, Sindh, Pakistan

Countries

Pakistan

Other Identifiers

ACTRN 12612000259842

Identifier Type: REGISTRY

Identifier Source: secondary_id

MIPV

Identifier Type: -

Identifier Source: org_study_id