Improving Rotavirus Vaccine Immune Response
Condition: Healthy Infants; Mothers
Study type: Interventional
Phase: Phase 3

Summary: 
      Rotavirus is the leading cause of severe gastroenteritis in infants and young children
      worldwide and is estimated to account for 600,000 deaths in children <5 years of age.
      However, live oral enteric vaccines (e.g. OPV, cholera vaccines, typhoid vaccine) have been
      less immunogenic in poor communities with high levels of malnutrition and poor sanitation.
      Rotavirus vaccines also appear to be less immunogenic in the setting where they are most
      needed. High maternal antibody (IgG) to rotavirus and breast feeding near the time of
      vaccination may inhibit rotavirus vaccine effectiveness. We propose a quick study to look at
      practical ways to improve the immunogenicity of rotavirus vaccine in our own setting in
      Bangladesh. The objectives are to assess if delaying Rotarix vaccination will improve the
      immune response to the vaccine and to assess if avoiding breastfeeding in the 45 minutes
      before and after vaccine administration will improve the immune response to administration of
      Rotarix vaccine. The study will be conducted in the urban Dhaka Mirpur Community, a setting
      where previous rotavirus vaccine immunogenicity studies have been successfully conducted. A
      total of 300 infant will be randomly assigned to one of the following groups: 1)
      Administration of Rotarix at 6 and 10 weeks co-administered with oral polio virus vaccine
      with no intervention in normal breastfeeding practices before and after receiving vaccine. 2)
      Administration of Rotarix at 6 and 10 weeks co-administered with oral polio virus.
      Breastfeeding will not be permitted 45 minutes prior to vaccine administration and 45 minutes
      after each vaccine administration. 3) Administration of Rotarix at 14 and 18 weeks
      co-administered with oral polio virus, with no intervention in normal breastfeeding practices
      before and after receiving vaccine. 4) Administration of Rotarix at 14 and 18 weeks
      co-administered with oral polio virus. Breastfeeding will not be permitted 45 minutes prior
      to vaccine administration and 45 minutes after each vaccine administration. Blood and stool
      samples will be collected from infants and breast milk from mothers. The primary outcome is
      to determine the sero-conversion rate of anti-rotavirus IgA in different groups of infants.
    

Detailed description: 
      The study will be conducted in a suburb of Dhaka in the area of Mirpur. Mirpur is one of the
      14 Thanas of Dhaka cities with a population of about one million in an area of 59 square
      kilometers. Mirpur Thana of Dhaka city is divided into several sections. There are 14
      sections in Mirpur Thana. The area is densely populated and located 20 minutes away from the
      lCDDR,B's Dhaka Hospital . The population is stable with low socioeconomic conditions. The
      average income in the slum areas of Mirpur is Tk.4200 (about US $ 62) per month per family.
      25% of fathers and 15% of mothers have more than 5 years of formal education. The study will
      be conducted in section 11 and 12 of Mirpur which has a population of about 500,000. We
      recently conducted phase I and II of the rotavirus vaccine study in this site. Several other
      studies (phase II ETEC, killed cholera vaccine) are ongoing in this area. Children will be
      identified through active surveillance of new births in the community and the study subjects
      will be recruited through home visits by the locally recruited field workers.

      2.2 .Design : Randomized intervention trial

      Study groups:

        1. Administration of Rotarix at 6 and 10 weeks co-administered with oral polio virus
           vaccine with no intervention in normal breastfeeding practices before and after
           receiving vaccine.

        2. Administration of Rotarix at 6 and 10 weeks co-administered with oral polio virus.
           Breastfeeding will not be permitted 45 minutes prior to vaccine administration and 45
           minutes after each vaccine administration.

        3. Administration of Rotarix at 14 and 18 weeks co-administered with oral polio virus, with
           no intervention in normal breastfeeding practices before and after receiving vaccine.

        4. Administration of Rotarix at 14 and 18 weeks co-administered with oral polio virus.
           Breastfeeding will not be permitted 45 minutes prior to vaccine administration and 45
           minutes after each vaccine administration.

      Samples collected:

        -  Blood draw at the time of first dose of Rotavirus vaccine and 4 weeks after the second
           dose

        -  Breast milk sample at 6 weeks for the mothers in study groups A and B, and at 14 weeks
           for mothers in study groups C and D (see below for groups).

        -  Stool sample prior to dose one and on day 3 and 7 after each dose to look for vaccine
           virus shedding
    

Intervention name(s): Rotavirus Vaccine & Breastfeeding; Rotavirus Vaccine & Breastfeeding; Rotavirus Vaccine & Breastfeeding; Rotavirus Vaccine & Breastfeeding
Intervention type(s): Biological; Biological; Biological; Biological
Intervention description(s): Administration of Rotarix at 6 and 10 weeks co-administered with oral polio virus vaccine with no intervention in normal breastfeeding practices before and after receiving vaccine.; Administration of Rotarix at 6 and 10 weeks co-administered with oral polio virus. Breastfeeding will not be permitted 45 minutes prior to vaccine administration and 45 minutes after each vaccine administration.; Administration of Rotarix at 14 and 18 weeks co-administered with oral polio virus, with no intervention in normal breastfeeding practices before and after receiving vaccine.; Administration of Rotarix at 14 and 18 weeks co-administered with oral polio virus. Breastfeeding will not be permitted 45 minutes prior to vaccine administration and 45 minutes after each vaccine administration.
Intervention MeSH terms: Vaccines
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Rotavirus; Immunogenicity; vaccine, Bangladesh