Diarrhea
Conditions
Brief summary
This is a randomized, double-blind, placebo-controlled clinical trial performed in Egyptian children 6-18 months of age. The primary aim of the study is to determine the protective efficacy of an oral, inactivated whole-cell enterotoxigenic Escherichia coli (ETEC) vaccine against diarrhea associated with excretion of ETEC that express a vaccine-shared antigen over a one year period of follow-up by active surveillance. The vaccine consists of a mixture of five formalin-killed ETEC bacteria expressing prevalent ETEC colonization factors and recombinant cholera toxin B-subunit (killed ETEC/rCTB vaccine). The placebo preparation is heat-killed Escherichia coli K-12 bacteria.
Interventions
BIOLOGICALETEC/rCTB vaccine
Cocktail of five whole-cell, formalin-inactivated ETEC strains (total of 10\^11 formalin-killed bacteria per dose) plus recombinant cholera toxin B-subunit (rCTB) (1 mg)
OTHERPlacebo
Heat-killed, nonpathogenic E. coli K-12 bacteria (total of 10\^11 heat-killed bacteria per dose)
Sponsors
U.S. Naval Medical Research Unit No. 3
Ministry of Health and Population, Egypt
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
International Vaccine Institute
Göteborg University
U.S. Army Medical Research and Development Command
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
6 Months to 18 Months
Healthy volunteers
Yes
Inclusion criteria
1. Willingness of parent to have the child participate; 2. Plans to reside in catchment area continuously for at least one year
Exclusion criteria
1. Global developmental delay 2. Severe malnutrition 3. Chronic bedridden status 4. Serious chronic disorder requiring chronic medication
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Time to first event of diarrhea due to vaccine-preventable ETEC (VP-ETEC) as defined below, and no other copathogen. | 365-day period starting 14 days after the third vaccination | Time to first event of diarrhea associated with excretion of VP-ETEC (defined as ETEC expressing heat-labile \[LT\] and heat-stable enterotoxin \[ST\], or ST and a vaccine-shared colonization factor \[i.e., CFA/I, CS1, CS2, CS3, CS4, and/or CS5\]) and no other copathogen. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time to first event of diarrhea due to ST-only ETEC expressing a vaccine-shared CF (ST-VCF-ETEC) as defined below, and no other copathogen.. | 365-day period starting 14 days after the third vaccination | Time to first event of diarrhea associated with excretion of ST-VCF-ETEC (defined as ETEC expressing ST-only plus any vaccine-shared colonization factor \[i.e., CFA/I, CS1, CS2, CS3, CS4, and/or CS5\]) and no other copathogen. |
| All events of diarrhea irrespective of etiology | 365-day period starting 14 days after the third vaccination | All events (i.e., initial plus recurrent) of diarrhea associated with excretion of any ETEC, irrespective of phenotype, and no other copathogen. |
| IgG seroconversion | Baseline serum specimen is collected before first dose and post-vaccination specimen collected 14 days after third dose | IgG seroconversion (≥ twofold increase in post-vaccination endpoint titer over baseline) against rCTB and vaccine-specific colonization factors CFA/I, CS2, CS4 |
| IgA seroconversion | Baseline serum specimen is collected before first dose and post-vaccination specimen collected 14 days after third dose | IgA seroconversion (≥ twofold increase in post-vaccination endpoint titer over baseline) against rCTB and selected vaccine-specific colonization factors CFA/I, CS2, CS4 |
| Number of solicited adverse events | 3-day period after each dose | (i.e., diarrhea, vomiting, fever by caregiver report, poor feeding, and irritability) |
Outcome results
None listed