| Purpose: |
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This study will validate a model for testing new vaccines designed to protect against
intestinal infections with enterotoxigenic Escherichia coli (ETEC). ETEC is one of the most
common causes of diarrhea in developing countries and is a common cause of travelers
diarrhea. Vaccines are now being developed and their development will be facilitated if we
have a valid model for testing these vaccines in human volunteers. We anticipate that the
new vaccines will be given to volunteers and they will then be given a dose of virulent ETEC
bacteria. If the vaccine is effective, the volunteers should not development diarrhea, but
if the vaccine is not effective, the volunteers will have diarrhea for a few days.
During this study, we will validate a minimum dose of virulent ETEC bacteria which is
sufficient to cause diarrhea in healthy adult volunteers and to identify conditions that can
make this model reliable.
We will also determine, in a follow-up group of volunteers, if being exposed to the ETEC
bacteria previously will protect against a subsequent illness when they are exposed to the
same bacteria a second time. We believe that the previously exposed group will be protected
and we will study the immune response to these exposures to help design vaccines that can
accomplish this kind of protection.
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| Criteria: |
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Inclusion Criteria:
1. Male or female between 18 and 45 years of age, inclusive.
2. General good health, as determined by physical exam, laboratory testing, and medical
history.
3. Laboratory values within acceptable range for CBC, ALT, and serum creatinine as
determined by PI.
4. Demonstrate comprehension of the protocol procedures and knowledge of ETEC illness by
passing a written examination (pass grade ≥ 70%)
5. Able and willing to sign an informed consent.
6. Available to participate for the length of the study.
7. Female only: Females of childbearing potential will use an effective method of
contraception during the study, including abstinence, hormonal contraception,
barrier, implantables or injectables.
Exclusion Criteria:
1. Presence of a clinically significant medical condition (including but not limited to
any chronic illnesses, immunosuppressive illness, cancer, diabetes, gastrointestinal
disease, such as peptic ulcer, symptoms or evidence of active gastritis or
gastroesophageal reflux disease, inflammatory bowel disease)
2. Evidence of IgA deficiency (serum IgA <5 or limit of detection of assay)
3. Evidence of HIV, HBV, HCV, by medical history or laboratory testing.
4. Symptoms consistent with Traveler's Diarrhea concurrent with travel to countries
where ETEC or cholera infection is endemic (most of the developing world) within two
years prior to receipt of investigational agent, OR planned travel to endemic
countries during the length of the trial.
5. History of significant psychiatric illness requiring hospitalization or any suicide
attempts within the past 2 years.
6. History of significant drug or alcohol abuse requiring hospitalization or
rehabilitation within the past 2 years.
7. Evidence of significant drug abuse, as determined by the Principal Investigator, on
toxicity screening.
8. Fewer than 3 stools per week or more than 3 stools per day as the usual frequency;
loose or liquid stools other than on an occasional basis.
9. History of allergic reaction to fluoroquinolones, cotrimoxazole, or
ampicillin/penicillin (excluded if allergic to two of three).
10. History of diarrhea in the 2 weeks prior to receipt of investigational agent.
11. Weekly use of laxatives or any agent that increases gastric pH.
12. Use of antibiotics during the 7 days prior to receipt of investigational agent.
13. Use of proton pump inhibitors, H2 blockers, or antacids within 48 hours of receipt of
investigational agent.
14. History of vaccination for or ingestion of ETEC, cholera, or LT toxin within 5
years.*
15. History of participation in prior ETEC H10407 research studies.*
16. Use of any other investigational product within 30 days preceding the receipt of
investigational agent, or planned use during the active study period.
17. Use of any medication known to affect the immune function (e.g., corticosteroids)
within 30 days preceding receipt of investigational agent or planned use during the
active study period. (Topical and intra-articular steroids will not exclude
subjects).
18. Any other condition, which in the opinion of the investigator, could affect subject
safety or interfere with the trial. |