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

NCT ID: NCT01375647

Last Updated: 2025-04-29

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

700 participants

Study Classification

INTERVENTIONAL

Study Start Date

2011-05-31

Study Completion Date

2014-11-30

Brief Summary

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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

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Conditions

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Rotavirus Diarrhea Vaccine Virus Shedding Tropical Enteropathy

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

FACTORIAL

Primary Study Purpose

PREVENTION

Blinding Strategy

SINGLE

Outcome Assessors

Study Groups

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Rotarix + No IPV (inactivated polio vaccine)

Oral Rotarix vaccine at 10 and 17 weeks of age and oral polio vaccine series

Group Type EXPERIMENTAL

Rotarix

Intervention Type BIOLOGICAL

Administered per protocol

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

Group Type EXPERIMENTAL

IPV (inactivated polio vaccine)

Intervention Type BIOLOGICAL

Administered per protocol

Rotarix

Intervention Type BIOLOGICAL

Administered per protocol

No Rotarix + No IPV (inactivated polio vaccine)

No Rotarix and oral polio vaccine series only

Group Type NO_INTERVENTION

No interventions assigned to this group

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

Group Type EXPERIMENTAL

IPV (inactivated polio vaccine)

Intervention Type BIOLOGICAL

Administered per protocol

Interventions

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IPV (inactivated polio vaccine)

Administered per protocol

Intervention Type BIOLOGICAL

Rotarix

Administered per protocol

Intervention Type BIOLOGICAL

Eligibility Criteria

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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.
Maximum Eligible Age

7 Days

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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Bill and Melinda Gates Foundation

OTHER

Sponsor Role collaborator

University of Virginia

OTHER

Sponsor Role collaborator

International Centre for Diarrhoeal Disease Research, Bangladesh

OTHER

Sponsor Role collaborator

Washington University School of Medicine

OTHER

Sponsor Role collaborator

Stanford University

OTHER

Sponsor Role collaborator

Centers for Disease Control and Prevention

FED

Sponsor Role collaborator

University of Vermont

OTHER

Sponsor Role lead

Responsible Party

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Beth Kirkpatrick

M.D.

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Beth Kirkpatrick, M.D.

Role: PRINCIPAL_INVESTIGATOR

University of Vermont

William Petri, M.D., Ph.D.

Role: PRINCIPAL_INVESTIGATOR

University of Virginia School of Medicine

Rashidul Haque, M.D., Ph.D.

Role: PRINCIPAL_INVESTIGATOR

International Center for Diarrhoeal Disease Research, Bangladesh

Locations

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International Centre for Diarrhoeal Disease Research, Bangladesh

Dhaka, , Bangladesh

Site Status

Countries

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Bangladesh

References

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Kirkpatrick BD, Colgate ER, Mychaleckyj JC, Haque R, Dickson DM, Carmolli MP, Nayak U, Taniuchi M, Naylor C, Qadri F, Ma JZ, Alam M, Walsh MC, Diehl SA; PROVIDE Study Teams; Petri WA Jr. The "Performance of Rotavirus and Oral Polio Vaccines in Developing Countries" (PROVIDE) study: description of methods of an interventional study designed to explore complex biologic problems. Am J Trop Med Hyg. 2015 Apr;92(4):744-51. doi: 10.4269/ajtmh.14-0518. Epub 2015 Feb 23.

Reference Type BACKGROUND
PMID: 25711607 (View on PubMed)

Colgate ER, Haque R, Dickson DM, Carmolli MP, Mychaleckyj JC, Nayak U, Qadri F, Alam M, Walsh MC, Diehl SA, Zaman K, Petri WA, Kirkpatrick BD. Delayed Dosing of Oral Rotavirus Vaccine Demonstrates Decreased Risk of Rotavirus Gastroenteritis Associated With Serum Zinc: A Randomized Controlled Trial. Clin Infect Dis. 2016 Sep 1;63(5):634-41. doi: 10.1093/cid/ciw346. Epub 2016 May 23.

Reference Type RESULT
PMID: 27217217 (View on PubMed)

Mychaleckyj JC, Haque R, Carmolli M, Zhang D, Colgate ER, Nayak U, Taniuchi M, Dickson D, Weldon WC, Oberste MS, Zaman K, Houpt ER, Alam M, Kirkpatrick BD, Petri WA Jr. Effect of substituting IPV for tOPV on immunity to poliovirus in Bangladeshi infants: An open-label randomized controlled trial. Vaccine. 2016 Jan 12;34(3):358-66. doi: 10.1016/j.vaccine.2015.11.046. Epub 2015 Nov 28.

Reference Type RESULT
PMID: 26643930 (View on PubMed)

Naylor C, Lu M, Haque R, Mondal D, Buonomo E, Nayak U, Mychaleckyj JC, Kirkpatrick B, Colgate R, Carmolli M, Dickson D, van der Klis F, Weldon W, Steven Oberste M; PROVIDE study teams; Ma JZ, Petri WA Jr. Environmental Enteropathy, Oral Vaccine Failure and Growth Faltering in Infants in Bangladesh. EBioMedicine. 2015 Sep 25;2(11):1759-66. doi: 10.1016/j.ebiom.2015.09.036. eCollection 2015 Nov.

Reference Type RESULT
PMID: 26870801 (View on PubMed)

Ciszewski J, Taniuchi M, Lee B, Colgate ER, Platts-Mills JA, Haque R, Zaman K, Lopman B, Petri WA Jr, Kirkpatrick BD, Rogawski McQuade ET. Differences in Rotavirus Shedding and Duration by Infant Oral Rotavirus Vaccination Status in Dhaka, Bangladesh, 2011-2014. J Infect Dis. 2024 Jul 25;230(1):e75-e79. doi: 10.1093/infdis/jiad502.

Reference Type DERIVED
PMID: 39052701 (View on PubMed)

Kupkova K, Shetty SJ, Haque R, Petri WA Jr, Auble DT. Histone H3 lysine 27 acetylation profile undergoes two global shifts in undernourished children and suggests altered one-carbon metabolism. Clin Epigenetics. 2021 Sep 26;13(1):182. doi: 10.1186/s13148-021-01173-8.

Reference Type DERIVED
PMID: 34565452 (View on PubMed)

Lin Y, Zhou J, Kumar S, Xie W, G Jensen SK, Haque R, Nelson CA, Petri WA Jr, Ma JZ. Group penalized generalized estimating equation for correlated event-related potentials and biomarker selection. BMC Med Res Methodol. 2020 Aug 31;20(1):221. doi: 10.1186/s12874-020-01103-x.

Reference Type DERIVED
PMID: 32867719 (View on PubMed)

Williams FB, Kader A, Colgate ER, Dickson DM, Carmolli M, Uddin MI, Sharmin S, Islam S, Bhuiyan TR, Alam M, Nayak U, Mychaleckyj JC, Petri WA, Haque R, Qadri F, Kirkpatrick BD, Lee B. Maternal Secretor Status Affects Oral Rotavirus Vaccine Response in Breastfed Infants in Bangladesh. J Infect Dis. 2021 Oct 13;224(7):1147-1151. doi: 10.1093/infdis/jiaa101.

Reference Type DERIVED
PMID: 32157282 (View on PubMed)

Rogawski ET, Platts-Mills JA, Colgate ER, Haque R, Zaman K, Petri WA, Kirkpatrick BD. Quantifying the Impact of Natural Immunity on Rotavirus Vaccine Efficacy Estimates: A Clinical Trial in Dhaka, Bangladesh (PROVIDE) and a Simulation Study. J Infect Dis. 2018 Mar 5;217(6):861-868. doi: 10.1093/infdis/jix668.

Reference Type DERIVED
PMID: 29514306 (View on PubMed)

Lee B, Carmolli M, Dickson DM, Colgate ER, Diehl SA, Uddin MI, Islam S, Hossain M, Rafique TA, Bhuiyan TR, Alam M, Nayak U, Mychaleckyj JC, McNeal MM, Petri WA, Qadri F, Haque R, Kirkpatrick BD. Rotavirus-Specific Immunoglobulin A Responses Are Impaired and Serve as a Suboptimal Correlate of Protection Among Infants in Bangladesh. Clin Infect Dis. 2018 Jul 2;67(2):186-192. doi: 10.1093/cid/ciy076.

Reference Type DERIVED
PMID: 29394355 (View on PubMed)

Lee B, Dickson DM, deCamp AC, Ross Colgate E, Diehl SA, Uddin MI, Sharmin S, Islam S, Bhuiyan TR, Alam M, Nayak U, Mychaleckyj JC, Taniuchi M, Petri WA Jr, Haque R, Qadri F, Kirkpatrick BD. Histo-Blood Group Antigen Phenotype Determines Susceptibility to Genotype-Specific Rotavirus Infections and Impacts Measures of Rotavirus Vaccine Efficacy. J Infect Dis. 2018 Apr 11;217(9):1399-1407. doi: 10.1093/infdis/jiy054.

Reference Type DERIVED
PMID: 29390150 (View on PubMed)

Upfill-Brown A, Taniuchi M, Platts-Mills JA, Kirkpatrick B, Burgess SL, Oberste MS, Weldon W, Houpt E, Haque R, Zaman K, Petri WA Jr. Nonspecific Effects of Oral Polio Vaccine on Diarrheal Burden and Etiology Among Bangladeshi Infants. Clin Infect Dis. 2017 Aug 1;65(3):414-419. doi: 10.1093/cid/cix354.

Reference Type DERIVED
PMID: 28444240 (View on PubMed)

Lu M, Zhou J, Naylor C, Kirkpatrick BD, Haque R, Petri WA Jr, Ma JZ. Application of penalized linear regression methods to the selection of environmental enteropathy biomarkers. Biomark Res. 2017 Mar 9;5:9. doi: 10.1186/s40364-017-0089-4. eCollection 2017.

Reference Type DERIVED
PMID: 28293424 (View on PubMed)

Taniuchi M, Platts-Mills JA, Begum S, Uddin MJ, Sobuz SU, Liu J, Kirkpatrick BD, Colgate ER, Carmolli MP, Dickson DM, Nayak U, Haque R, Petri WA Jr, Houpt ER. Impact of enterovirus and other enteric pathogens on oral polio and rotavirus vaccine performance in Bangladeshi infants. Vaccine. 2016 Jun 8;34(27):3068-3075. doi: 10.1016/j.vaccine.2016.04.080. Epub 2016 May 3.

Reference Type DERIVED
PMID: 27154394 (View on PubMed)

Other Identifiers

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PROVIDE

Identifier Type: -

Identifier Source: org_study_id

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