Predictors of Poor Immune Response to Rotavirus Vaccine in Infants (PPIR)

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®.

Study Overview

• Status: Completed
• Conditions: Innate Immune Response
• Intervention / Treatment: Other: Breastfeeding

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 400
• Phase: Not Applicable

Contacts and Locations

Study Locations

• India
  • Delhi
    • New Delhi, Delhi, India, 110016
      • Centre for Health Research and Development Society for Applied Studies

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 month to 1 month (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. At least one parent(s) or legally acceptable representative's consent for participation and are able to understand study procedures
2. Subjects aged 6 to 7 weeks at recruitment
3. No plans to move in the next 4 months
4. Weight for age not ≤ -3 SD of WHO child growth standards

Exclusion Criteria:

1. Infant not breastfed
2. Administration of rotavirus vaccine in the past
3. Known immunodeficiency disease, including HIV infection in the subject or the mother
4. Known chronic enteric disease
5. Diarrhea on the day of enrollment (temporary exclusion)
6. Any illness requiring hospitalization (temporary exclusion)
7. Any other conditions which in the judgment of the investigator warrant exclusion (e.g. no exclusion criteria but seems 'ill', investigators suspects neglect)

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Breastfeeding; Breastfeeding Encouraged	Other: Breastfeeding; breastfeeding encouraged versus withheld
Active Comparator: Breastfeeding Withheld	Other: Breastfeeding; breastfeeding encouraged versus withheld

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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	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

Other Outcome Measures

Outcome Measure	Time Frame
Concentration of anti-VP6 antibodies in subjects and maternal serum at baseline and in subjects 4 weeks after the second dose of Rotarix®. Geometric mean titers of anti-VP6 IgG antibodies in maternal serum at baseline	upto 14-18 weeks of age

Collaborators and Investigators

• Sponsor: Society for Applied Studies
• Collaborators: Norwegian Institute of Public Health; Christian Medical College, Vellore, India
• Investigators: Principal Investigator: Temsunaro R Chandola, MBBS MSc Epi, Research Scientist, SAS; Principal Investigator: Nita Bhandari, MBBS, PhD, Joint Director, SAS; Principal Investigator: Sunita Taneja, MBBS, PhD, Research Coordinator, SAS; Principal Investigator: Gagandeep Kang, MD PhD FRCPath, Professor and Head,The Wellcome Trust Research Laboratory,Christian Medical College; Principal Investigator: Tor A Strand, MD, PhD, Adjunct Professor, CIH

Publications and helpful links

General Publications

• Rongsen-Chandola T, Strand TA, Goyal N, Flem E, Rathore SS, Arya A, Winje BA, Lazarus R, Shanmugasundaram E, Babji S, Sommerfelt H, Vainio K, Kang G, Bhandari N. Effect of withholding breastfeeding on the immune response to a live oral rotavirus vaccine in North Indian infants. Vaccine. 2014 Aug 11;32 Suppl 1:A134-9. doi: 10.1016/j.vaccine.2014.04.078.
• Rongsen-Chandola T, Winje BA, Goyal N, Rathore SS, Mahesh M, Ranjan R, Arya A, Rafiqi FA, Bhandari N, Strand TA. Compliance of mothers following recommendations to breastfeed or withhold breast milk during rotavirus vaccination in North India: a randomized clinical trial. Trials. 2014 Jun 28;15:256. doi: 10.1186/1745-6215-15-256.

Study record dates

Study Major Dates

• Study Start: October 1, 2012
• Primary Completion (Actual): May 1, 2013
• Study Completion (Actual): May 1, 2013

Study Registration Dates

• First Submitted: September 28, 2012
• First Submitted That Met QC Criteria: October 3, 2012
• First Posted (Estimate): October 4, 2012

Study Record Updates

• Last Update Posted (Estimate): June 26, 2013
• Last Update Submitted That Met QC Criteria: June 25, 2013
• Last Verified: June 1, 2013

More Information

Terms related to this study

• Keywords: infants; rotavirus vaccine; immune response
• Other Study ID Numbers: SAS/RCN/201208