Immunity to Polio Vaccines in Malnourished InfantsPhase 4MIPVNCT01695798
IPV in Moderate to Severe Chronic Malnourished 9-12 Month Old Children in Karachi.
A Phase 4 study testing Injectable polio vaccine and Bivalent oral polio vaccine in people with Immunity to Polio Vaccines in Malnourished Infants and Immunity to Polio Vaccines in Non-malnourished Infants, run by Aga Khan University at 1 site in Pakistan.
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… Read more about this study
- Who is it for?
- Ages 9 to 12 monthsHealthy volunteers can take part
- Conditions the study is for
- Immunity to Polio Vaccines in Malnourished Infants, Immunity to Polio Vaccines in Non-malnourished Infants
- What is being tested?
- Injectable polio vaccine and Bivalent oral polio vaccine
- Type of treatment
- Vaccines, Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 840 participants
- Where
- 1 sitePakistan
- Study dates
- Oct 2012to Oct 2013
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 9 to 12 months
- All sexes
- Healthy volunteers accepted
- Child
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
About this study
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.
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).
Read the 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
- Being tested
- Injectable polio vaccine and Bivalent oral polio vaccine
- Keywords
- poliomyelitis, oral polio vaccine, OPV, seroconversion, mucosal immunity, malnutrition, IPV, Inactivated polio vaccine, Pakistan
- Medical subject headings
- Poliomyelitis, HIV Seropositivity, Malnutrition
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Injectable polio vaccine and Bivalent oral polio vaccineBiological
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
| Study group | Role | What they receive |
|---|---|---|
| Chronic malnourished bOPV | No intervention | This arm will receive only bOPV |
| Malnourished IPV+bOPV | Experimental | This arm will receive IPV and bOPV Receives: Biological: Injectable polio vaccine and Bivalent oral polio vaccine |
| Normally nourished bOPV | No intervention | This arm will receive only bOPV |
| Normally nourished IPV+bOPV | Experimental | This arm will receive both IPV and bOPV Receives: Biological: Injectable polio vaccine and Bivalent oral polio vaccine |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 12 months
Compare the effect of IPV on seropositivity between chronically malnourished and normally nourished 9-12 month old infants.
Measured: 12 months
Secondary outcomes (1)
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.
Measured: 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Sep 2012 (estimated)
- Study startOct 2012
- Primary completionSep 2013
- Study completionOct 2013
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Immunity to Polio Vaccines in Malnourished InfantsStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 840 participants (actual)
Sponsor and investigators
- Lead sponsor
- Aga Khan University
- Sponsor type
- University, hospital or other
- Collaborators
- World Health Organization, National Institutes of Health (NIH)
- Responsible party
- Principal investigator, Anita Kaniz Mehdi Zaidi, Aga Khan University
- Investigators
- Anita K.M Zaidi, MBBS, SM, Principal investigator, Aga Khan UniversityAli F Saleem, MBBS, MCR, FCPS, Study director, Aga Khan UniversityFarheen Quadri, MBBS, MSCR, Study director, Aga Khan University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01695798
- Sponsor's protocol ID
- MIPV
- Other IDs
- ACTRN 12612000259842
- Acronym
- MIPV
- Status last verified
- Jan 2014
- First submitted
- 27 Sep 2012
- Last updated
- 16 Jan 2014
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 16 Jan 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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.
- ClinicalTrials.gov ID
- NCT01695798
- Acronym / sponsor ID
- MIPV / MIPV
- Conditions
- Immunity to Polio Vaccines in Malnourished Infants, Immunity to Polio Vaccines in Non-malnourished Infants
- Keywords
- poliomyelitis, oral polio vaccine, OPV, seroconversion, mucosal immunity, malnutrition, IPV, Inactivated polio vaccine
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 840 participants (actual)
- Lead sponsor
- Aga Khan UniversityUniversity, hospital or other
- Collaborators
- World Health Organization, National Institutes of Health (NIH)
- Study start
- Oct 2012
- Primary completion
- Sep 2013 (actual)
- Study completion
- Oct 2013 (actual)
- First posted
- 28 Sep 2012 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Chronic malnourished bOPV | No intervention | –This arm will receive only bOPV |
| Malnourished IPV+bOPV | Experimental | Biological: Injectable polio vaccine and Bivalent oral polio vaccineThis arm will receive IPV and bOPV |
| Normally nourished bOPV | No intervention | –This arm will receive only bOPV |
| Normally nourished IPV+bOPV | Experimental | Biological: Injectable polio vaccine and Bivalent oral polio vaccineThis arm will receive both IPV and bOPV |
Who may qualify
- Ages
- 9 to 12 months
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child
Key inclusion criteria (3 listed)
- 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
Key exclusion criteria (6 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Injectable polio vaccine and Bivalent oral polio vaccineOne 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 | Biological | Malnourished IPV+bOPV, Normally nourished IPV+bOPV |
Primary outcome
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
Compare the effect of IPV on seropositivity between chronically malnourished and normally nourished 9-12 month old infants.
Time frame: 12 months
1 secondary outcome
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
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Jan 2014.
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Anita K.M Zaidi, MBBS, SM principal investigator
Aga Khan University
Ali F Saleem, MBBS, MCR, FCPS study director
Aga Khan University
Farheen Quadri, MBBS, MSCR study director
Aga Khan University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Injectable polio vaccine and Bivalent oral polio vaccine in people with Immunity to Polio Vaccines in Malnourished Infants and Immunity to Polio Vaccines in Non-malnourished Infants, run by Aga Khan University at 1 site in Pakistan.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 16 Jan 2014. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Pakistan. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the 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) (time frame: 12 months). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 Jan 2014.