Achlorhydria, Infection
Conditions
Brief summary
The study proposes to test whether chronic infection with Helicobacter pylori protects individuals from symptomatic infection with enteropathogenic E. coli. The study will also evaluate the effect of gastric acidity in this relationship.
Detailed description
Because H. pylori is an enteric infection, its prevalence may be linked to exposure to other enteric pathogens. Results of observational studies on the association between H. pylori and gastroenteritis, however, have been conflicting. Some have shown increased incidence of diarrhea in children with H. pylori infection, with one study attributing 11% of diarrhea cases to H. pylori. Other studies found no association, and still others found a protective effect of H. pylori against gastroenteritis. Dissecting out confounding from true physiological associations can be difficult in observational studies. To better elucidate the association between H. pylori and gastroenteritis, we performed a direct challenge experiment with a well-characterized gastrointestinal pathogen, enteropathogenic Escherichia coli (EPEC). EPEC is a leading cause of infantile gastroenteritis in the world and has a long history of safe use in human experiments. It is also acid sensitive: in our laboratory less than 0.001% of inoculated EPEC organisms survived at pH 2.5. Our goal was to test the hypothesis that chronic infection with H. pylori increases the risk of diarrheal illness after direct challenge with EPEC.
Interventions
BIOLOGICALBiological intervention: Enteropathogenic E. coli
5x10\^8 or 1x10\^9 organisms of EPEC were administered to all participants.
Sponsors
Stanford University
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
35 Years to 59 Years
Healthy volunteers
Yes
Inclusion criteria
Healthy
Exclusion criteria
prior gastrointestinal disease prior treatment of H. pylori infection immune suppression or deficiency history of cancer, diabetes, or other co-morbidity
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Development of Diarrhea | 48 hours |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Intensity of Gastrointestinal Symptoms | 48 hours | Composite gastrointestinal symptom score was on a scale from 0 (no symptoms) to 15 (severe symptoms). This composite was the sum of 5 self-reported, symptom scores, each ranging from 0 (none) to 3 (severe). The self-reported symptoms that subjects scored were: malaise, headache, nausea, vomiting, and loose stool. |
Countries
United States
Participant flow
Recruitment details
Patients were recruited for the study from 2005 to 2008. Enrollment began 6/2005 and ended 5/2008. Healthy individuals were sought with no chronic medical conditions or symptoms.
Pre-assignment details
Participants were assigned to one of two groups: Helicobacter pylori positive, or Helicobacter pylori negative. Assignment was based on results of H. pylori serology and Urea Breath Test. Test results had to be concordant for group assignment.
Participants by arm
| Arm | Count |
|---|---|
| H. Pylori Negative Participants who tested negative for H. pylori infection. | 26 |
| H. Pylori Positive Participants who tested H. pylori positive | 19 |
| Total | 45 |
Baseline characteristics
| Characteristic | H. Pylori Positive | Total | H. Pylori Negative |
|---|---|---|---|
| Age, Continuous | 49.4 years STANDARD_DEVIATION 6.7 | 48.6 years STANDARD_DEVIATION 7 | 48.1 years STANDARD_DEVIATION 7.3 |
| BMI | 28.7 kg/m2 STANDARD_DEVIATION 3.8 | 27.7 kg/m2 STANDARD_DEVIATION 4.3 | 27 kg/m2 STANDARD_DEVIATION 4.5 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 12 Participants | 17 Participants | 5 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 7 Participants | 28 Participants | 21 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Gastric pH, Median | 1.6 units on a scale | 1.5 units on a scale | 1.5 units on a scale |
| Hypochlorhydric | 7 participants | 9 participants | 2 participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 2 Participants | 4 Participants | 2 Participants |
| Race (NIH/OMB) Black or African American | 3 Participants | 5 Participants | 2 Participants |
| Race (NIH/OMB) More than one race | 1 Participants | 2 Participants | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 13 Participants | 34 Participants | 21 Participants |
| Sex: Female, Male Female | 4 Participants | 15 Participants | 11 Participants |
| Sex: Female, Male Male | 15 Participants | 30 Participants | 15 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 26 | 0 / 19 |
| serious Total, serious adverse events | 0 / 26 | 0 / 19 |
Outcome results
Primary
Development of Diarrhea
Time frame: 48 hours
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| H. Pylori Negative | Development of Diarrhea | 5 participants |
| H. Pylori Positive | Development of Diarrhea | 6 participants |
Secondary
Intensity of Gastrointestinal Symptoms
Composite gastrointestinal symptom score was on a scale from 0 (no symptoms) to 15 (severe symptoms). This composite was the sum of 5 self-reported, symptom scores, each ranging from 0 (none) to 3 (severe). The self-reported symptoms that subjects scored were: malaise, headache, nausea, vomiting, and loose stool.
Time frame: 48 hours
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| H. Pylori Negative | Intensity of Gastrointestinal Symptoms | 3 units on a scale |
| H. Pylori Positive | Intensity of Gastrointestinal Symptoms | 3 units on a scale |