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

April 25, 2025 updated by: Beth Kirkpatrick, University of Vermont

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

700

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Bangladesh
      • Dhaka, Bangladesh
        • International Centre for Diarrhoeal Disease Research, Bangladesh

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

No older than 1 week (Child)

Accepts Healthy Volunteers

Yes

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Prevention
  • Allocation: Randomized
  • Interventional Model: Factorial Assignment
  • Masking: Single

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Rotarix + No IPV (inactivated polio vaccine)
Oral Rotarix vaccine at 10 and 17 weeks of age and oral polio vaccine series
Biological: Rotarix
Administered per protocol
Experimental: Rotarix + 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
Biological: Rotarix
Administered per protocol
Biological: IPV (inactivated polio vaccine)
Administered per protocol
No Intervention: No Rotarix + No IPV (inactivated polio vaccine)
No Rotarix and oral polio vaccine series only
Experimental: No Rotarix + IPV (inactivated polio vaccine)
No Rotarix vaccine and IPV (inactivated polio vaccine) boost in place of oral polio vaccine dose at 39 weeks
Biological: IPV (inactivated polio vaccine)
Administered per protocol

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Presence of Fecal Shedding of Polio Vaccine Virus Determined by Culture (Polio Trial)
Time Frame: 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
25 days following week 52 visit
Number of Participants With One or More Episodes of Rotavirus-associated Diarrhea (Rotavirus Trial)
Time Frame: 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.
Birth to one year

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Duration of Fecal Shedding of Polio Vaccine Virus, Each Sabin Type (Polio Trial)
Time Frame: 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
from day 4 to day 25 following the week 52 visit
Community Fecal Shedding of Polio Vaccine Virus Just Prior to Oral Polio Vaccine Dose at 52 Weeks (Polio Trial)
Time Frame: post 52 weeks
Only 8 infants were shedding at baseline so results are not presented for this outcome due to insufficient data
post 52 weeks
Presence of Fecal Polio Virus Shedding Within the Three Sabin Strains (Polio Trial)
Time Frame: 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)
25 days following week 52 visit
Serum Neutralizing Antibody Response (Polio Trial)
Time Frame: 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
18-40 weeks
Total Number of Diarrheal Episodes (Rotavirus Trial)
Time Frame: 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
Birth to one year
Total Duration of Rotavirus-associated Diarrheal Episodes (Rotavirus Trial)
Time Frame: 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
Birth to one year

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Vermont

Collaborators

Washington University School of Medicine
Bill and Melinda Gates Foundation
Stanford University
Centers for Disease Control and Prevention
University of Virginia
International Centre for Diarrhoeal Disease Research, Bangladesh

Investigators

  • Principal Investigator: William Petri, M.D., Ph.D., University of Virginia School of Medicine
  • Principal Investigator: Rashidul Haque, M.D., Ph.D., International Center for Diarrhoeal Disease Research, Bangladesh
  • Principal Investigator: Beth Kirkpatrick, M.D., University of Vermont

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

May 1, 2011

Primary Completion (Actual)

October 1, 2014

Study Completion (Actual)

November 1, 2014

Study Registration Dates

First Submitted

June 3, 2011

First Submitted That Met QC Criteria

June 15, 2011

First Posted (Estimated)

June 17, 2011

Study Record Updates

Last Update Posted (Actual)

April 29, 2025

Last Update Submitted That Met QC Criteria

April 25, 2025

Last Verified

April 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • PROVIDE

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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