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| ID | Type | Description | Link |
|---|---|---|---|
| CHR (H.22.03.10.28.A2) | Other Identifier | JHSPH IRB |
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| Name | Class |
|---|---|
| Henry M. Jackson Foundation for the Advancement of Military Medicine | OTHER |
| Naval Medical Research Center | FED |
| Walter Reed Army Institute of Research (WRAIR) | FED |
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| H10407 | Experimental | H10407 |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| H10407 | 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 |
| Measure | Description | Time Frame |
|---|---|---|
| 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. | 6 months |
| Measure | Description | Time Frame |
|---|---|---|
| To measure mucosal and systemic immune response to the somatic and toxin antigens of the H10407 strain. | 6 months |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Robin McKenzie, M.D. | Johns Hopkins University | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| General Clinical Research Center | Baltimore | Maryland | 21205 | United States |
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| ID | Term |
|---|---|
| D003967 | Diarrhea |
| ID | Term |
|---|---|
| D012817 | Signs and Symptoms, Digestive |
| D012816 | Signs and Symptoms |
| D013568 | Pathological Conditions, Signs and Symptoms |
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| U.S. Army Medical Research and Development Command |
| FED |
We will initially study the effects of a 1x109 dose of H10407 (in 5 subjects) and then proceed to the dose-finding portion of the trial to study the effects of low (5x108) or higher doses (5x109) of the CS17 expressing strains (total of 20 subjects)
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