Does the Fecal Microbiome Influence Rotarix Immunogenicity

Nested Case-control Analysis of the Influence of the Microbiome on Rotavirus Vaccine Immunogenic Response in Infants in Karachi, Pakistan

This is a proposal for a nested case-control study within an ongoing rotavirus vaccine immunogenicity clinical trial Karachi, Pakistan. The primary study aim is to compare the fecal microbiota composition and diversity of infants who do (control) and do not (case) demonstrate immune seroconversion to rotavirus vaccination. The infants will be matched for vaccination dose, age and breast-feeding practices.

Study Overview

• Status: Completed
• Conditions: Rotavirus Infections; Reaction - Vaccine Nos; Intestinal Bacteria Flora Disturbance

• Study Type: Observational
• Enrollment (Actual): 76

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 4 weeks and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

The study will be nested within an existing rotavirus immunogenicity study being conducted in Karachi, Pakistan (clinicaltrials.gov: NCT01199874) . The physical setting is a peri-urban slum outside of Karachi, primarily populated by fishermen. Parents and legal guardians of infants participating in NCT01199874 will provide new informed consent for inclusion in this study.

Description

Inclusion Criteria:

• 6 weeks 0 days to 7 weeks 6 days age at the time of enrollment.
• Healthy infant free of chronic or serious medical condition as determined by history and physical exam at time of enrollment into in the study.
• Written informed consent obtained from the parents or guardians.
• Availability of baseline fecal sample collected before Rotarix vaccination
• Written informed consent obtained from the parents or guardians for nested study

Exclusion Criteria:

• Hypersensitivity to any of the vaccine components
• Use of any investigational drug or vaccine other than the study vaccine within 30 days of first dose of study vaccine or during the study.
• Use of any immunosuppressive drugs.
• Previous intussusceptions or abdominal surgery.
• Enrollment in any other trial (besides NCT01199874).
• Birth weight less than 1500 grams; or if birth weight is unknown, weight less than 2000 grams on or before 28 days.
• Immunoglobulin and/or blood products use since birth or during the study period. Nested study additional exclusion criteria:
• Positive serum anti-rotavirus Immunoglobulin A (> 20 U/ml) at 6 weeks of age, indicative of prior rotavirus infection

Study Plan

How is the study designed?

Design Details

• Observational Models: Case-Control
• Time Perspectives: Prospective

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort
Case: non-rotavirus seroconverters; Infants not demonstrating seroconversion to rotavirus vaccination, as measured anti-RV Immunoglobulin A < 20 U/ml
Control: rotavirus seroconverters; Infants demonstrating seroconversion to rotavirus vaccination, as measured by anti-rotavirus Immunoglobulin A > 20 U/ml

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
microbiome diversity (Shannon's index) and composition (relative abundance)	Microbiota composition will be measured by calculating and comparing a % of the phylogenetic groups present in both groups Diversity will be measured by calculating a comparing a Shannon's reciprocal index of diversity, 1/D in both groups The relative abundance of microbial groups will be measured by calculating and comparing the ribosomal ribonucleic acid gene copy per gram of feces over time in both groups	at 6 weeks of age, pre-rotavirus vaccination

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
microbiome diversity (Shannon's index) and composition (relative abundance)	Microbiota composition post vaccination will be measured by calculating and comparing a % of the phylogenetic groups present in both groups Diversity post vaccination will be measured by calculating a comparing a Shannon's reciprocal index of diversity, 1/D in both groups The relative abundance of microbial groups post vaccination will be measured by calculating and comparing the ribosomal ribonucleic acid gene copy per gram of feces over time in both groups	at 1 to 3 years of age post-rotavirus vaccination

Collaborators and Investigators

• Sponsor: Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
• Collaborators: University of Padova; Centers for Disease Control and Prevention; Aga Khan University; Wageningen University and Research
• Investigators: Principal Investigator: Vanessa C Harris, MD, Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)

Study record dates

Study Major Dates

• Study Start: September 1, 2013
• Primary Completion (Actual): November 1, 2013
• Study Completion (Actual): November 1, 2013

Study Registration Dates

• First Submitted: June 10, 2014
• First Submitted That Met QC Criteria: August 19, 2014
• First Posted (Estimate): August 20, 2014

Study Record Updates

• Last Update Posted (Estimate): August 20, 2014
• Last Update Submitted That Met QC Criteria: August 19, 2014
• Last Verified: August 1, 2014

More Information

Terms related to this study

• Keywords: immunogenicity; gut microbiome; microbiome; rotavirus; enteric vaccine; vaccine immunogenicity; rotavirus vaccine
• Additional Relevant MeSH Terms: RNA Virus Infections; Virus Diseases; Infections; Reoviridae Infections; Rotavirus Infections
• Other Study ID Numbers: AIGHD-CSP2013-001a

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No