Clinical trial NCT02220439: Does the Fecal Microbiome Influence Rotarix Immunogenicity
Official title: Nested Case-control Analysis of the Influence of the Microbiome on Rotavirus Vaccine Immunogenic Response in Infants in Karachi, Pakistan
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Rotavirus Infections
Reaction - Vaccine Nos
Intestinal Bacteria Flora Disturbance
Keywords: rotavirus
immunogenicity
enteric vaccine
vaccine immunogenicity
rotavirus vaccine
gut microbiome
microbiome
Lead sponsor: Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
Sponsor class: OTHER
Collaborators: name: Aga Khan University
name: Centers for Disease Control and Prevention
name: University of Padova
name: Wageningen University and Research
First posted: 2014-08-20
Enrollment: 76
Sex: ALL
Minimum age (years): 4
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_CONTROL
Time perspective: PROSPECTIVE
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.

Brief summary: 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.


Eligibility criteria: 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

Primary outcomes:
measure: microbiome diversity (Shannon's index) and composition (relative abundance)
timeFrame: at 6 weeks of age, pre-rotavirus vaccination
Secondary outcomes:
measure: microbiome diversity (Shannon's index) and composition (relative abundance)
timeFrame: at 1 to 3 years of age post-rotavirus vaccination
Other outcomes:
Locations:
Study officials:
affiliation: Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
name: Vanessa C Harris, MD
role: PRINCIPAL_INVESTIGATOR
References: