Exploration of the Biologic Basis for Underperformance of Oral Polio and Rotavirus Vaccines in Bangladesh

Phase 3

Completed

• Conditions: Rotavirus Diarrhea; Vaccine Virus Shedding; Tropical Enteropathy
• Interventions: Biological: Rotarix; Biological: IPV (inactivated polio vaccine); Biological: IPV

• Registration Number: NCT01375647
• Lead Sponsor: University of Vermont

Brief Summary

Oral polio and rotavirus vaccines are significantly less effective in children living in the developing world. Tropical enteropathy, which is associated with intestinal inflammation, decreased absorption and increased permeability, may contribute substantially to oral vaccine failure in developing country settings. Other possible causes of oral vaccine underperformance include malnutrition, interference with maternal or breastmilk antibodies, changes in gut microbiota, and genetic susceptibility.

Primary Objective: to determine whether tropical enteropathy impairs the efficacy of oral polio and rotavirus vaccines in children in Bangladesh.

Secondary Objectives: 1) to determine the impact of an IPV (inactivated polio vaccine) boost on the efficacy of OPV (oral polio vaccine) and 2) to determine the efficacy of Rotarix oral rotavirus vaccine to prevent rotavirus diarrhea

The polio and rotavirus randomized clinical trials are embedded as secondary objectives within the exploratory study of tropical enteropathy. The primary and secondary outcome measures are relevant to the randomized clinical trials.

Detailed Description

Not available

Study Timeline

• Study Start: 2011-05
• Study First Submitted: 2011-06-03
• Study First Submitted QC: 2011-06-15
• Study First Posted: 2011-06-17
• Primary Completion: 2014-10
• Study Completion: 2014-11
• Results First Submitted: 2017-11-29
• Status Verified: 2025-04
• Results First Submitted QC: 2025-04-25
• Last Update Submitted: 2025-04-25
• Results First Posted: 2025-04-29
• Last Update Posted: 2025-04-29

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 700

Inclusion Criteria

1. Mother willing to sign informed consent form.
2. Healthy infant aged 0 to 7 days old.
3. No obvious congenital abnormalities or birth defects.
4. No abnormal (frequency and consistency) stools since birth.
5. Stable household with no plans to leave the area for the next one year.

Exclusion Criteria

1. Parents are not willing to have child vaccinated at the field clinic.
2. Parents are not willing to have child's blood drawn.
3. Parents are planning to enroll child into another clinical study during the time period of this trial.
4. Mother not willing to have blood drawn and breast milk extracted.
5. Parents not willing to have field research assistant in home two times per week.
6. History of seizures or other apparent neurologic disorders.
7. Infant received any vaccines before start of study, except Bacillus Calmette-Guerin (BCG).
8. Infant has any sibling currently or previously enrolled in this study, including a twin.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: FACTORIAL

Arm && Interventions

Group	Intervention	Description
Rotarix + No IPV (inactivated polio vaccine)	Rotarix	Oral Rotarix vaccine at 10 and 17 weeks of age and oral polio vaccine series
Rotarix + IPV (inactivated polio vaccine)	IPV (inactivated polio vaccine)	Oral Rotarix vaccine at 10 and 17 weeks of age plus IPV (inactivated polio vaccine) boost in place of oral polio vaccine dose at 39 weeks
Rotarix + IPV (inactivated polio vaccine)	Rotarix	Oral Rotarix vaccine at 10 and 17 weeks of age plus IPV (inactivated polio vaccine) boost in place of oral polio vaccine dose at 39 weeks
No Rotarix + IPV (inactivated polio vaccine)	IPV (inactivated polio vaccine)	No Rotarix vaccine and IPV (inactivated polio vaccine) boost in place of oral polio vaccine dose at 39 weeks
Rotarix + No IPV	Rotarix	Randomized to receive rotarix vaccine but no IPV boost
Rotarix + with IPV boost	IPV	Randomized to receive both rotarix vaccine and IPV boost
Rotarix + with IPV boost	Rotarix	Randomized to receive both rotarix vaccine and IPV boost
No Rotarix + with IPV boost	IPV	Randomized to receive no rotarix vaccine but to receive IPV boost

Primary Outcome Measures

Name	Time	Method
Presence of Fecal Shedding of Polio Vaccine Virus Determined by Culture (Polio Trial)	25 days following week 52 visit	Any Sabin type poliovirus in any fecal samples at days 0, 4, 11, 18 or 25 following week 52 dose
Number of Participants With One or More Episodes of Rotavirus-associated Diarrhea (Rotavirus Trial)	Birth to one year	Diarrheal episode defined as presence of 3 or more abnormally loose stools in 24h period with \>=72 hours separating episodes. Rotavirus antigen detected by ELISA in diarrheal stool.

Secondary Outcome Measures

Name	Time	Method
Duration of Fecal Shedding of Polio Vaccine Virus, Each Sabin Type (Polio Trial)	from day 4 to day 25 following the week 52 visit	Shedding index, calculated as duration days multiplied by mean log (shedding amount) for Sabin types 1, 2, and 3.; Outcome is conditioned on infants with at least one detection by quantitative PCR (qPCR) at day 4,11,18, or 25. If shedding data point was missing it was assumed that the infant was not shedding at that time.; Lower shedding index is better outcome
Community Fecal Shedding of Polio Vaccine Virus Just Prior to Oral Polio Vaccine Dose at 52 Weeks (Polio Trial)	post 52 weeks	Only 8 infants were shedding at baseline so results are not presented for this outcome due to insufficient data
Presence of Fecal Polio Virus Shedding Within the Three Sabin Strains (Polio Trial)	25 days following week 52 visit	Frequency (%) of infants excreting poliovirus at any of the 5 time points (day 0, 4,11,18, 25) post week 52 oral polio vaccine dose.; Presence of poliovirus is determined by polymerase chain reaction (PCR)
Serum Neutralizing Antibody Response (Polio Trial)	18-40 weeks	Seropositive defined as antibodies present at ≥1:8 dilution, antibody titers \<1:8 were seronegative.; Non-seroconversions are those who did not seroconvert between week 18 (post oral polio vaccine dose 2) and week 40, adjusted for residual maternal antibody
Total Number of Diarrheal Episodes (Rotavirus Trial)	Birth to one year	A diarrheal episode is defined as the presence of 3 or more abnormally loose stools in a 24 hour period with at least 72 diarrhea-free hours separating distinct episodes
Total Duration of Rotavirus-associated Diarrheal Episodes (Rotavirus Trial)	Birth to one year	A diarrheal episode is defined as the presence of 3 or more abnormally loose stools in a 24 hour period with at least 72 diarrhea-free hours separating distinct episodes.; Rotavirus positive specimens were determined by ELISA Those with no rotavirus diarrheal episodes are counted as duration 0

Trial Locations

Locations (1)

International Centre for Diarrhoeal Disease Research, Bangladesh; 🇧🇩 Dhaka, Bangladesh