Improving Rotavirus Vaccine Immune Response

Mothers Clinical Trial

Official title:

Improving the Immune Response to Rotavirus Vaccine

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01825109
• Other study ID #: PR-09070
• Status: Completed
• Phase: Phase 3
• First received: April 2, 2013
• Last updated: April 4, 2013
• Start date: July 2010
• Est. completion date: December 2011

Study information

• Verified date: December 2009
• Source: International Centre for Diarrhoeal Disease Research, Bangladesh
• Contact: n/a
• Is FDA regulated: No
• Health authority: Bangladesh: Ethical Review Committee
• Study type: Interventional

Clinical Trial 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.

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 300
• Est. completion date: December 2011
• Est. primary completion date: April 2011
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 1 Month to 45 Years

Eligibility

Inclusion Criteria:

• male or female,

• aged 6 weeks at the time of enrollment,

• written informed consent,

• free of chronic or serious medical condition as determined by history and physical exam and plan to stay in community for at least 6 months

Exclusion Criteria:

• fever (>38 C),

• acute or chronic illness,

• use of antimicrobial drug within previous 14 days,

• hypersensitivity to any of the vaccine components (see vaccine composition),

• use of any investigational drug during previous 30 days,

• any uncorrected congenital malformation of the gastrointestinal tract,

• use of any immunosuppressing drugs during the last 14 days (likelihood is remote),

• any evidence by physical exam of immunosuppresing condition,

• administration of gamma globulin or any other blood product,

• previous intussusception or abdominal surgery.

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Healthy Infants
• Mothers

Intervention

Biological:
• Rotavirus Vaccine & Breastfeeding
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.
• Rotavirus Vaccine & Breastfeeding
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.
• Rotavirus Vaccine & Breastfeeding
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.
• Rotavirus Vaccine & Breastfeeding
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.

Locations

Country	Name	City	State
Bangladesh	Mirpur	Dhaka

Sponsors (5)

Lead Sponsor	Collaborator
International Centre for Diarrhoeal Disease Research, Bangladesh	Centers for Disease Control and Prevention, European Centre for Disease Prevention and Control, SE-171, Stockholm, National Institutes of Health (NIH), The Swedish Institute for Infectious Disease Control, SE-171 82 SOLNA

Country where clinical trial is conducted

Bangladesh, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Immunogenicity of Rotavirus Vaccine	Sero-conversion rate of anti-rotavirus IgA	24 months	Yes
Secondary	anti-rotavirus IgA	Geometric mean concentration of anti-rotavirus IgA Enterovirus excretion in children at the time of vaccination	24 months	Yes