<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT01695798</url>
  </required_header>
  <id_info>
    <org_study_id>MIPV</org_study_id>
    <secondary_id>ACTRN 12612000259842</secondary_id>
    <nct_id>NCT01695798</nct_id>
  </id_info>
  <brief_title>IPV in Moderate to Severe Chronic Malnourished 9-12 Month Old Children in Karachi.</brief_title>
  <acronym>MIPV</acronym>
  <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.</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Aga Khan University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>World Health Organization</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>National Institutes of Health (NIH)</agency>
      <agency_class>NIH</agency_class>
    </collaborator>
  </sponsors>
  <source>Aga Khan University</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Chronic malnutrition is associated with lack of effective gut immunity which is a possible&#xD;
      explanation for why we see polio cases among a proportion of children who have received 7 or&#xD;
      more doses of OPV.Our proposed idea is to evaluate if IPV antigen given later in life may act&#xD;
      together to boost humoral and mucosal immunity in children belonging to low-income background&#xD;
      in Karachi who have moderate to severe chronic malnutrition (height for age Z score less than&#xD;
      -2SD). We also intend to compare eIPV + OPV with OPV only in non-malnourished infants at 9&#xD;
      -12 month of age. Thus, the proposed study is a combination of two trials, with study&#xD;
      population stratified by nutritional status, each with a reference arm (bOPV) and an&#xD;
      experimental arm (bOPV plus IPV).&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The development of chronic malnutrition is a complex interplay of multiple factors; including&#xD;
      genetic predisposition and a whole host of environmental insults. In the urban squatter and&#xD;
      peri-urban settlement environments of Karachi where the Aga Khan University (AKU) has&#xD;
      established surveillance programs, half of all infants have moderate to severe chronic&#xD;
      malnutrition (height for age Z score less than -2 SD) by the time they are 9 -12 months old.&#xD;
      IPV has the advantage of parenteral route, thereby bypassing the damaged gut mucosa of&#xD;
      malnourished children. It also does not cause the rare vaccine-associated paralysis. Its&#xD;
      effectiveness depends on stimulation of serum (blood) neutralizing antibodies that block the&#xD;
      spread of poliovirus to the central nervous system. The main disadvantages that have&#xD;
      precluded IPV use in low-income countries is high cost, difficulty in adding another&#xD;
      injectable vaccine in the EPI schedule at 6, 10, and 14 weeks, and lack of ability to induce&#xD;
      a strong mucosal immune response and therefore prevent enteral infection. Additionally,&#xD;
      maternal antibodies at this early age neutralize IPV quite effectively. However, as the&#xD;
      median age of polio in Pakistan is 15 months for poliovirus type 1 and 18 months for&#xD;
      poliovirus type 3, it may be feasible to give a single IPV dose at an older age, avoiding the&#xD;
      effects of maternal antibodies and boosting immunity against polio before the majority of&#xD;
      these children enter their risk period in Pakistan. Enhanced potency IPV (eIPV) with higher&#xD;
      antigen content yields greater than 90% seropositivity against all 3 types after one dose and&#xD;
      100% seropositivity after two doses. Thus using eIPV combined with OPV at 9 - 12 months in&#xD;
      moderate to severe chronically malnourished infants may provide improved seroconversion as&#xD;
      well as some stimulation of the mucosal immune response. Our proposed idea is to evaluate if&#xD;
      IPV antigen given later in life may act together to boost humoral and mucosal immunity in&#xD;
      children belonging to low-income background in Karachi who have moderate to severe chronic&#xD;
      malnutrition (height for age Z score less than -2SD). We also intend to compare eIPV + OPV&#xD;
      with OPV only in non-malnourished infants at 9 -12 month of age. Thus, the proposed study is&#xD;
      a combination of two trials, with study population stratified by nutritional status, each&#xD;
      with a reference arm (bOPV) and an experimental arm (bOPV plus IPV).&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>October 2012</start_date>
  <completion_date type="Actual">October 2013</completion_date>
  <primary_completion_date type="Actual">September 2013</primary_completion_date>
  <phase>Phase 4</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Prevention</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>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)</measure>
    <time_frame>12 months</time_frame>
    <description>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</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Compare the effect of IPV on seropositivity between chronically malnourished and normally nourished 9-12 month old infants.</measure>
    <time_frame>12 months</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Compare mucosal immunity in moderate to severe chronically malnourished and non-malnourished infant who receive bivalent OPV at 9-12 months of age</measure>
    <time_frame>12 months</time_frame>
    <description>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.</description>
  </secondary_outcome>
  <number_of_arms>4</number_of_arms>
  <enrollment type="Actual">840</enrollment>
  <condition>Immunity to Polio Vaccines in Malnourished Infants</condition>
  <condition>Immunity to Polio Vaccines in Non-malnourished Infants</condition>
  <arm_group>
    <arm_group_label>Chronic malnourished bOPV</arm_group_label>
    <arm_group_type>No Intervention</arm_group_type>
    <description>This arm will receive only bOPV</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Malnourished IPV+bOPV</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>This arm will receive IPV and bOPV</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Normally nourished bOPV</arm_group_label>
    <arm_group_type>No Intervention</arm_group_type>
    <description>This arm will receive only bOPV</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Normally nourished IPV+bOPV</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>This arm will receive both IPV and bOPV</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Injectable polio vaccine and Bivalent oral polio vaccine</intervention_name>
    <description>One dose of IPV given IM (arm, thigh) to infant aged 9-12 month after randomization.&#xD;
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</description>
    <arm_group_label>Malnourished IPV+bOPV</arm_group_label>
    <arm_group_label>Normally nourished IPV+bOPV</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Infant aged 9 - 12 months of age&#xD;
&#xD;
          -  Resident of the study area for last 3 month at the time of enrolment&#xD;
&#xD;
          -  Parent/guardian provides informed consent&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Infant already enrolled in any other polio intervention study.&#xD;
&#xD;
          -  Infant found acutely ill at the time of enrolment, requiring emergent medical care&#xD;
&#xD;
          -  Infant with moderate and severe acute malnutrition, defined by a very low weight for&#xD;
             height (below -2z and -3z scores of the median WHO growth standards respectively).&#xD;
&#xD;
          -  Refusal of blood testing&#xD;
&#xD;
          -  Receipt of supplementary dose of OPV within 4 weeks of first study visit&#xD;
&#xD;
          -  Infant with certain medical conditions i.e., cerebral palsy, syndromic infants,&#xD;
             infants on corticosteroids because of any medical illness, thrombocytopenia&#xD;
             (contraindication of intramuscular injections), malignancies and infant with primary&#xD;
             immunodeficiency&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>9 Months</minimum_age>
    <maximum_age>12 Months</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Anita K.M Zaidi, MBBS, SM</last_name>
    <role>Principal Investigator</role>
    <affiliation>Aga Khan University</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Ali F Saleem, MBBS, MCR, FCPS</last_name>
    <role>Study Director</role>
    <affiliation>Aga Khan University</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Farheen Quadri, MBBS, MSCR</last_name>
    <role>Study Director</role>
    <affiliation>Aga Khan University</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Aga Khan University</name>
      <address>
        <city>Karachi</city>
        <state>Sindh</state>
        <zip>74800</zip>
        <country>Pakistan</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Pakistan</country>
  </location_countries>
  <verification_date>January 2014</verification_date>
  <study_first_submitted>September 27, 2012</study_first_submitted>
  <study_first_submitted_qc>September 27, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 28, 2012</study_first_posted>
  <last_update_submitted>January 14, 2014</last_update_submitted>
  <last_update_submitted_qc>January 14, 2014</last_update_submitted_qc>
  <last_update_posted type="Estimate">January 16, 2014</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Aga Khan University</investigator_affiliation>
    <investigator_full_name>Anita Kaniz Mehdi Zaidi</investigator_full_name>
    <investigator_title>Professor</investigator_title>
  </responsible_party>
  <keyword>poliomyelitis</keyword>
  <keyword>oral polio vaccine</keyword>
  <keyword>OPV</keyword>
  <keyword>seroconversion</keyword>
  <keyword>mucosal immunity</keyword>
  <keyword>malnutrition</keyword>
  <keyword>IPV</keyword>
  <keyword>Inactivated polio vaccine</keyword>
  <keyword>Pakistan</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Poliomyelitis</mesh_term>
    <mesh_term>Malnutrition</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Vaccines</mesh_term>
  </intervention_browse>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT01695798
org study id: MIPV
secondary id: ACTRN 12612000259842
nct id: NCT01695798
lead sponsor: 
collaborator: 
collaborator: 
has dmc: Yes
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).
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).
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Prevention
masking: None (Open Label)
measure: 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
description: 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
measure: Compare the effect of IPV on seropositivity between chronically malnourished and normally nourished 9-12 month old infants.
time frame: 12 months
measure: 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
description: 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.
arm group label: Chronic malnourished bOPV
arm group type: No Intervention
description: This arm will receive only bOPV
arm group label: Malnourished IPV+bOPV
arm group type: Experimental
description: This arm will receive IPV and bOPV
arm group label: Normally nourished bOPV
arm group type: No Intervention
description: This arm will receive only bOPV
arm group label: Normally nourished IPV+bOPV
arm group type: Experimental
description: This arm will receive both IPV and bOPV
intervention type: Biological
intervention name: Injectable polio vaccine and Bivalent oral polio vaccine
description: 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
arm group label: Malnourished IPV+bOPV
arm group label: Normally nourished IPV+bOPV
criteria: 
gender: All
minimum age: 9 Months
maximum age: 12 Months
healthy volunteers: Accepts Healthy Volunteers
last name: Anita K.M Zaidi, MBBS, SM
role: Principal Investigator
affiliation: Aga Khan University
last name: Ali F Saleem, MBBS, MCR, FCPS
role: Study Director
affiliation: Aga Khan University
last name: Farheen Quadri, MBBS, MSCR
role: Study Director
affiliation: Aga Khan University
facility: 
country: Pakistan
responsible party type: Principal Investigator
investigator affiliation: Aga Khan University
investigator full name: Anita Kaniz Mehdi Zaidi
investigator title: Professor
mesh term: Poliomyelitis
mesh term: Malnutrition
mesh term: Vaccines