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

Immunity to Polio Vaccines in Malnourished Infants Clinical Trial

— MIPV  

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.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01695798
• Other study ID #: MIPV
• Secondary ID: ACTRN 1261200025
• Status: Completed
• Phase: Phase 4
• First received: September 27, 2012
• Last updated: January 14, 2014
• Start date: October 2012
• Est. completion date: October 2013

Study information

• Verified date: January 2014
• Source: Aga Khan University
• Contact: n/a
• Is FDA regulated: No
• Health authority: Switzerland:World Health Organization
• Study type: Interventional

Clinical Trial 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).

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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 840
• Est. completion date: October 2013
• Est. primary completion date: September 2013
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 9 Months to 12 Months

Eligibility

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 Design

Allocation: Randomized, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Prevention

Related Conditions & MeSH terms

• Immunity to Polio Vaccines in Malnourished Infants
• Immunity to Polio Vaccines in Non-malnourished Infants
• Malnutrition

Intervention

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

Locations

Country	Name	City	State
Pakistan	Aga Khan University	Karachi	Sindh

Sponsors (3)

Lead Sponsor	Collaborator
Aga Khan University	National Institutes of Health (NIH), World Health Organization

Country where clinical trial is conducted

Pakistan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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)	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	No
Primary	Compare the effect of IPV on seropositivity between chronically malnourished and normally nourished 9-12 month old infants.		12 months	No
Secondary	Compare mucosal immunity in moderate to severe chronically malnourished and non-malnourished infant who receive bivalent OPV at 9-12 months of age	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	No