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

NCT ID: NCT00198796

Last Updated: 2017-04-11

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 5 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2005-09-30
• Study Completion Date: 2007-05-30

Brief Summary

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.

Detailed Description

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.

Conditions

Diarrhea

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: SCREENING
• Blinding Strategy: NONE

Study Groups

H10407

H10407

Group Type: EXPERIMENTAL

H10407

Intervention Type: BIOLOGICAL

The primary objective of the proposed clinical investigation is to validate a dose for ETEC H10407 that will cause diarrhea in 50% or more of subjects without causing high output diarrhea

Interventions

H10407

The primary objective of the proposed clinical investigation is to validate a dose for ETEC H10407 that will cause diarrhea in 50% or more of subjects without causing high output diarrhea

Intervention Type: BIOLOGICAL

Other Intervention Names

Experimental

Eligibility Criteria

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).

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 45 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Henry M. Jackson Foundation for the Advancement of Military Medicine

OTHER

Sponsor Role: collaborator

Naval Medical Research Center

FED

Sponsor Role: collaborator

Walter Reed Army Institute of Research (WRAIR)

FED

Sponsor Role: collaborator

U.S. Army Medical Research and Development Command

FED

Sponsor Role: collaborator

Johns Hopkins Bloomberg School of Public Health

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Robin McKenzie, M.D.

Role: PRINCIPAL_INVESTIGATOR

Johns Hopkins University

Locations

General Clinical Research Center

Baltimore, Maryland, United States

Countries

United States

Other Identifiers

CIR #193

Identifier Type: -

Identifier Source: org_study_id

CHR (H.22.03.10.28.A2)

Identifier Type: OTHER

Identifier Source: secondary_id