Predictors of Poor Immune Response to Rotavirus Vaccine in Infants

Study Overview
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Brief Summary
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This will be a randomized study with the primary objective of assessing the impact of withholding versus encouraging breastfeeding on the immunogenicity of Rotarix® in infants. Enrolled subjects will all be administered Rotarix®, at ages 6 to 7 weeks, and at10 -14 weeks. The subjects will be randomized into one of the two study arms. In one of the group caregivers will be advised to breastfeed immediately prior to and after each dose of the vaccine while in the other group caregivers will be advised to withhold breastfeeding for 30 minutes before and after each dose of the vaccine. The other childhood vaccines i.e. OPV and Pentavalent will be administered at least 30 minutes after administration of Rotarix®, The enrolled subjects will be followed up for 4 weeks after the 2nd dose of Rotarix®.

Detailed Description
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Infants ≤7 weeks and pregnant women will be identified through a household survey.Families of infants aged 6-7 weeks will be called to the study clinic for consenting, screening and enrollment.All enrolled subjects will be administered 2 doses of Rotarix® at 6 to 7 weeks and at 10-14 weeks of age. Other childhood vaccines will also be offered. At enrollment, a blood specimen and breast milk specimen will be obtained from the mother and a blood, salivary and stool specimens will be obtained from the subject before administering the Rotarix® vaccine. At the time of the 2nd administration, a breast milk specimen will be obtained from the mother and a salivary specimen will be obtained from the subject before administering the Rotarix® vaccine. At 28 days (±) 5 after the 2nd dose of Rotarix® vaccine, a blood, salivary and stool specimen will be obtained from the subject. Whenever the family comes to the study clinic at 6-7 weeks, consent will be administered and a clinical examination conducted.If the family is willing for the mother and the child to be part of the study and the child meets the eligibility criteria, the child will be enrolled. Depending on the group allocation the mothers will be advised to withhold or encourage breastfeeding for 30 minutes before and after receipt of Rotarix®. subjects will be observed for 30 minutes after receipt of the vaccines to assess for immediate adverse events. All minor illnesses that do not require hospital referral will be managed by the study physician using current practices. All hospitalizations and deaths will be reported and reviewed by an Independent Safety Monitor.

Official Title
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Predictors of Poor Immune Response to Rotavirus Vaccine in Infants

Conditions
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Innate Immune Response

Intervention / Treatment
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* Other: Breastfeeding


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: At least one parent(s) or legally acceptable representative's consent for participation and are able to understand study procedures Subjects aged 6 to 7 weeks at recruitment No plans to move in the next 4 months Weight for age not ≤ -3 SD of WHO child growth standards Exclusion Criteria: Infant not breastfed Administration of rotavirus vaccine in the past Known immunodeficiency disease, including HIV infection in the subject or the mother Known chronic enteric disease Diarrhea on the day of enrollment (temporary exclusion) Any illness requiring hospitalization (temporary exclusion) Any other conditions which in the judgment of the investigator warrant exclusion (e.g. no exclusion criteria but seems 'ill', investigators suspects neglect)

Ages Eligible for Study
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Minimum Age: 6 Weeks
Maximum Age: 7 Weeks

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Breastfeeding<br>Breastfeeding Encouraged | Other: Breastfeeding<br>* breastfeeding encouraged versus withheld<br>|
| Active Comparator: Breastfeeding Withheld<br>Breastfeeding Withheld | Other: Breastfeeding<br>* breastfeeding encouraged versus withheld<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of subjects who seroconvert as measured by a 4-fold rise in serum anti-VP6 IgA antibodies between baseline and 4 weeks after the second dose of Rotarix®. |  | 14-18 weeks of age | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Concentration of anti-VP6 antibodies in saliva of subjects before the first and second dose of Rotarix®. Proportion of subjects with enteric pathogens detected in stools. Vitamin D status of subjects enrolled in the study. |  | 14-18 weeks of age | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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immune response, infants, rotavirus vaccine