Dose-finding Study of WS6788A, DS37-4 and H10407 Enterotoxigenic Escherichia Coli (ETEC) Challenge Strains

Phase 1CompletedNCT00198796

Johns Hopkins Bloomberg School of Public Health5 enrolled

Overview

Five subjects will be admitted to the General Clinical Research Center (GCRC). The next day they will eat a light breakfast, fast for 90 minutes, ingest ETEC strain H10407, and fast for 90 more minutes. After this challenge they will be monitored closely , and all stools will be collected, graded and weighed. On Day 5, or sooner if indicated, they will begin antibiotics to eradicate the challenge strain. They will be scheduled for discharge on Day 7 but may leave a few days earlier if early antibiotic treatment is given. Hypothesis: A challenge dose of 10(9) colony forming unit (CFU) of ETEC strain H10407, will cause diarrhea in at least 60% of subjects.

The rationale for validation H10407 in the challenge study proposed at Johns Hopkins University is that this initial challenge study will support additional challenge studies planned for the future. In these future studies, a bovine milk immunoglobulin containing high levels of antibodies specific for colonization factor antigen (CFA/I) or CFA/I-derived colonization factor will be investigated as a potential oral prophylaxis to neutralize subsequent challenge against CFA/I-expressing H10407 in the clinical setting. The goal here is therefore to validate a challenge dose of 1x109 h10407 organisms in the hands of the Johns Hopkins investigative team and to then use this dose in the future prophylaxis/challenge studies. Challenge doses equal to or comparable to the 1x109 dose proposed for the Johns Hopkins University (JHU) study have been used in 6 of the 9 challenge studies that have been done with the H10407 strain. The subsequent challenge studies using H10407 will be registered as part of other protocols.

Study Type

INTERVENTIONAL

Allocation

Purpose

SCREENING

Masking

NONE

Enrollment

Eligibility

Sex: ALLMin age: 18 YearsMax age: 45 YearsHealthy volunteers:

Medical Language ↔ Plain English

Inclusion Criteria: * Healthy adults age 18 to 45 years old who are willing to participate, complete training on ETEC and diarrhea and procedures of the protocol, pass the test documenting knowledge of the study, and give informed consent. Exclusion Criteria: 1. age\<18 or \>45 years 2. Chronic illness, chemical dependency, or significant medical illness as determined by the investigator. 3. immunosuppressive condition or IgA (Immunoglobulin A) deficiency 4. HIV antibody positive 5. hepatitis B surface antigen positive 6. hepatitis C antibody positive 7. travel to ETEC endemic area within 2 years 8. vaccination or other exposure to ETEC, cholera, or heat labile toxin (LT) toxin within 3 years 9. pregnancy as defined by + serum or urine - human chorionic gonadotropin (HCG) on the day before immunization 10. inability to pass the written examination 11. use of antibiotic, H2 blocking agent or proton pump inhibitor within 7 days of challenge 12. regular use of laxatives antacids or other agents to lower stomach acidity 13. significant abnormality in screening lav hematology and chemistry tests as determined by the investigator. 14. significant abnormality on EKG for those 40 to 50 years old as determined by the investigator. 15. allergy to quinolones, penicillin's and Bactrim. 16. abnormal stool pattern (fewer than 3 stools per week or more than 3 stools per day).

Outcomes

Primary Outcomes

To validate a dose for ETEC H10407 that will cause diarrhea in 50% or more of subjects without causing high output diarrhea, as determined by stool output volumes or signs and symptoms associated with hypovolemia.

Time frame: 6 months

Secondary Outcomes

To measure mucosal and systemic immune response to the somatic and toxin antigens of the H10407 strain.