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

Sponsor

University of Vermont (Other)

Overall Status

Completed

CT.gov ID

NCT01375647

Collaborator

Bill and Melinda Gates Foundation (Other), University of Virginia (Other), International Centre for Diarrhoeal Disease Research, Bangladesh (Other), Washington University School of Medicine (Other), Stanford University (Other), Centers for Disease Control and Prevention (U.S. Fed)

700

Enrollment

Location

Arms

42.1

Duration (Months)

16.6

Patients Per Site Per Month

Study Details

Study Description

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 inactivated polio vaccine (IPV) boost on the efficacy of oral polio vaccine and 2) to determine the efficacy of 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.

Condition or Disease	Intervention/Treatment	Phase
Rotavirus Diarrhea Vaccine Virus Shedding Tropical Enteropathy	Biological: IPV Biological: Rotarix	Phase 3

Study Design

Study Type:

Interventional

Actual Enrollment :

700 participants

Allocation:

Randomized

Intervention Model:

Factorial Assignment

Masking:

Single (Outcomes Assessor)

Primary Purpose:

Prevention

Official Title:

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

Study Start Date :

May 1, 2011

Actual Primary Completion Date :

Oct 1, 2014

Actual Study Completion Date :

Nov 1, 2014

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Rotarix + No IPV Randomized to receive rotarix vaccine but no IPV boost	Biological: Rotarix Administered per protocol
Experimental: Rotarix + with IPV boost Randomized to receive both rotarix vaccine and IPV boost	Biological: IPV Administered per protocol Biological: Rotarix Administered per protocol
No Intervention: No Rotarix + No IPV Randomized to receive neither rotarix vaccine nor IPV boost
Experimental: No Rotarix + with IPV boost Randomized to receive no rotarix vaccine but to receive IPV boost	Biological: IPV Administered per protocol

Outcome Measures

Primary Outcome Measures

Presence of fecal shedding of polio vaccine virus determined by culture (polio trial) [25 days following week 52 visit]
One or more episodes of rotavirus-associated diarrhea (rotavirus trial) [Birth to one year]

Secondary Outcome Measures

Duration of fecal shedding of polio vaccine virus (polio trial) [25 days following week 52 visit]
Community fecal shedding of polio vaccine virus just prior to one year OPV dose (polio trial) [52 weeks]
Presence and duration of fecal polio virus shedding within the three individual virus strains (polio trial) [25 days following week 52 visit]
Serum neutralizing antibody response (polio trial) [40 weeks and 53 weeks]
Total number of diarrheal episodes (rotavirus trial) [Birth to one year]
Total duration of rotavirus-associated diarrheal episodes (rotavirus trial) [Birth to one year]

Eligibility Criteria

Criteria

Ages Eligible for Study:

N/A to 7 Days

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

Inclusion Criteria:

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.

Exclusion Criteria:

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	International Centre for Diarrhoeal Disease Research, Bangladesh	Dhaka		Bangladesh

Sponsors and Collaborators

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

Investigators

Principal Investigator: 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