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

NCT01375647 | Completed Phase 3 Results

• 1 other identifier: PROVIDE
• Study Type: interventional
• Target: 700
• Locations: 1 country
• Sites: 1

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.

Conditions

Rotavirus Diarrhea; Vaccine Virus Shedding; Tropical Enteropathy

Keywords

Oral Vaccines; Vaccine Responsiveness; Tropical Enteropathy

Outcome Measures

Primary Outcomes (2)

• Presence of Fecal Shedding of Polio Vaccine Virus Determined by Culture (Polio Trial)

  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)

  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 Outcomes (6)

• Duration of Fecal Shedding of Polio Vaccine Virus, Each Sabin Type (Polio Trial)

  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)

  post 52 weeks

• Presence of Fecal Polio Virus Shedding Within the Three Sabin Strains (Polio Trial)

  25 days following week 52 visit

• Serum Neutralizing Antibody Response (Polio Trial)

  18-40 weeks

• Total Number of Diarrheal Episodes (Rotavirus Trial)

  Birth to one year

Study Arms (4)

Rotarix + No IPV (inactivated polio vaccine)

EXPERIMENTAL

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

Biological: Rotarix

Rotarix + IPV (inactivated polio vaccine)

EXPERIMENTAL

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: IPV (inactivated polio vaccine); Biological: Rotarix

No Rotarix + No IPV (inactivated polio vaccine)

NO INTERVENTION

No Rotarix and oral polio vaccine series only

No Rotarix + IPV (inactivated polio vaccine)

EXPERIMENTAL

No Rotarix vaccine and IPV (inactivated polio vaccine) boost in place of oral polio vaccine dose at 39 weeks

Biological: IPV (inactivated polio vaccine)

Interventions

IPV (inactivated polio vaccine) BIOLOGICAL

Administered per protocol

No Rotarix + IPV (inactivated polio vaccine); Rotarix + IPV (inactivated polio vaccine)

Rotarix BIOLOGICAL

Administered per protocol

Rotarix + IPV (inactivated polio vaccine); Rotarix + No IPV (inactivated polio vaccine)

Eligibility Criteria

• Age: Up to 7 Days
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17)

You may qualify if:

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

You may not qualify if:

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

Sponsors & Collaborators

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

Study Sites (1)

International Centre for Diarrhoeal Disease Research, Bangladesh

Dhaka, Bangladesh

Location

Related Publications (14)

• 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.

  PMID: 25711607 BACKGROUND

• 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.

  PMID: 27217217 RESULT

• 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.

  PMID: 26643930 RESULT

• 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.

  PMID: 26870801 RESULT

• 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.

  PMID: 39052701 DERIVED

• 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.

  PMID: 34565452 DERIVED

• 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.

  PMID: 32867719 DERIVED

• 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.

  PMID: 32157282 DERIVED

• 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.

  PMID: 29514306 DERIVED

• 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.

  PMID: 29394355 DERIVED

• 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.

  PMID: 29390150 DERIVED

• 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.

  PMID: 28444240 DERIVED

• 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.

  PMID: 28293424 DERIVED

• 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.

  PMID: 27154394 DERIVED

MeSH Terms

Conditions

Sprue, Tropical

Interventions

Poliovirus Vaccine, Inactivated; RIX4414 vaccine

Condition Hierarchy (Ancestors)

Malabsorption Syndromes; Intestinal Diseases; Gastrointestinal Diseases; Digestive System Diseases; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Vaccines, Inactivated; Vaccines; Biological Products; Complex Mixtures; Poliovirus Vaccines; Viral Vaccines

Results Point of Contact

• Title: Dorothy M Dickson, MSc
• Organization: University of Vermont

dorothy.dickson@med.uvm.edu

802 656 9296

Study Officials

• Beth Kirkpatrick, M.D.

  University of Vermont

  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

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: FACTORIAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: M.D.

Study Record Dates

• First Submitted: June 3, 2011
• First Posted: June 17, 2011
• Study Start: May 1, 2011
• Primary Completion: October 1, 2014
• Study Completion: November 1, 2014
• Last Updated: April 29, 2025
• Results First Posted: April 29, 2025

Record last verified: 2025-04

Locations

BA (1)