NCT02870751

Human Challenge Model With ST-only Enterotoxigenic Escherichia Coli

Developing A Human Challenge Model For Evaluating Vaccines Against ST-producing Enterotoxigenic Escherichia Coli

• Status: Unknown
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 30 (estimated)
• Sponsor: University of Bergen · Academic / Other
• Sex: All
• Age: 18 Years – 45 Years
• Healthy volunteers: Accepted

Summary

Heat stable toxin (ST) producing ETEC strains are important causes of childhood diarrhea in many countries. Vaccine candidates targeting ST are in development. A human challenge model using an epidemiologically relevant enterotoxigenic E.coli (ETEC) strain expressing ST, but not other diarrhea inducing toxins like heat labile toxin (LT), is necessary to perform an early and efficient evaluation of an ST-toxoid based vaccine. In this controlled human infection study the investigators will assess the safety of a ST-only producing ETEC strain and the dose needed to achieve an attack rate of 70% in healthy human volunteers.

Detailed description

The investigators have evaluated the ST-only ETEC strain TW10722 in volunteers previously, and will also evaluate the ETEC strain TW11681, an ETEC family 8, serotype O19:H45, expressing STh, CFA/I, and CS21. These strains have been selected because it is a good representative of one of the most important ETEC families commonly associated with childhood ETEC diarrhea. The TW10722 will also be evaluated at higher dose if TW11681 does not work well. After screening including routine blood sampling, intestinal lavage and pre-challenge sampling will be done. Volunteers will then be admitted three at a time to Haukeland University Hospital and isolated before receiving the oral bacterial inoculum doses, starting with 10\^6 and increasing one log per round until a safe dose that elicits diarrhoea is found. Fine adjustment of the dose needed for a diarrhea attack rate of 70% will then be done in the remaining volunteers. Volunteers will be monitored for a range of symptoms, stool output and adverse events. Antibiotic treatment will be administered at certain predetermined severities of diarrheal disease, or after 5 days to eradicate the ETEC infection in all volunteers before leaving the hospital. Volunteers will be monitored and sampled again at day 10, 28 and 365 after infection. Serum, plasma, stool, intestinal lavage and PBMC samples will be obtained before, during and after the ETEC infection to evaluate immune responses and potential correlates of protection.

Conditions

• Diarrhea, Infantile

Interventions

Type	Name	Description
BIOLOGICAL	TW11681 or TW10722

Timeline

• Start date: 2016-05-01
• Primary completion: 2018-12-01
• Completion: 2019-09-01
• First posted: 2016-08-17
• Last updated: 2018-09-11

Locations

1 site across 1 country: Norway