Clostridium Difficile Infection
Conditions
Keywords
Clostridium Difficile Infection, Proton Pump Inhibitors, Histamine-2 Receptor Antagonists, Gastroesophageal Reflux Disease
Brief summary
The colonic microbiome is essential in health and disease, and is highly dynamic during the first several years of life. Proton pump inhibitors (PPIs) and histamine-2 receptor antagonists (H2RAs) are widely used in children, but the effects of PPIs and H2RAs on the pediatric colonic microbiome are unknown. This study will determine whether acid suppression with these medications affects the microbiome of otherwise healthy children who are prescribed acid suppression for gastroesophageal reflux disease (GERD), and determine the duration and magnitude of microbiome changes.
Detailed description
Otherwise healthy children age 0-4 years old who are being considered for acid suppressive therapy for GERD will be eligible for this study. Subjects donate samples before and after being treated with PPIs or H2RAs (must donate at least 2 baseline pre-PPI samples to be eligible for final analysis). 30 total children who complete the study (anticipated 10 who receive lifestyle modification and 20 who receive PPIs or H2RAs). All children will donate 6 stools on or about weeks 0, 4, 12, 20, 38, and 64. The primary outcome will be a significant change in the overall diversity of the colonic microbiome after 8 weeks of PPIs or H2RAs (i.e., from week 12 to week 4), compared to after 4 weeks of lifestyle management.
Interventions
DRUGOmeprazole (suspension)
1 mg/kg/day
OTHERLifestyle Modification
Standard lifestyle modification: small meals, upright feeding, elevation of the head of the bed
Sponsors
Columbia University
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
0 Years to 4 Years
Healthy volunteers
No
Inclusion criteria
* Zero to 4 years old * Being considered for PPI or H2RA treatment for refractory GERD * Parent is able to give informed consent
Exclusion criteria
* Prevalent C. difficile infection (excluded via stool PCR at week 0) * Use of systemic antibiotics within the past 90 days * Use of acid suppression medications within the past 90 days (antacids allowed if none within the last 7 days) * Increased risk for fracture due to vitamin D deficiency or other causes * Chronic gastrointestinal disease (e.g. inflammatory bowel disease, celiac disease, microscopic colitis, malabsorptive conditions, short gut syndrome) * Congenital deficiency in immunity (e.g., such as IgA deficiency) * Cystic fibrosis * Significant dynamic or uncontrolled comorbidity such as HIV or malignancy * Use of medications with potential interaction with PPIs
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Change in Fecal Microbiome Diversity, Assessed by Bray-Curtis Index Comparing Those Who Received Acid Suppression Medications to Those Who Received Lifestyle Modifications | From week 12 to week 4 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percent Subjects Eating High Fiber Diet | Up to Week 64 | At each study visit, we will assess the effects of longterm diet on the microbiome by using the Harvard-Willett Food Frequency Questionnaire. Using this data, we will classify each subject as low vs high fiber. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Omeprazole (Suspension) Open-label, with all subjects receiving omeprazole
Omeprazole (suspension): 1 mg/kg/day | 3 |
| Lifestyle Modification Treated with lifestyle modification (upright feeding, smaller meals, elevation of the head of the bed, etc.)
Lifestyle Modification: Standard lifestyle modification: small meals, upright feeding, elevation of the head of the bed | 4 |
| Total | 7 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lost to Follow-up | 2 | 4 |
Baseline characteristics
| Characteristic | Omeprazole (Suspension) | Lifestyle Modification | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 3 Participants | 4 Participants | 7 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 2 Participants | 3 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 2 Participants | 2 Participants | 4 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Region of Enrollment United States | 3 participants | 4 participants | 7 participants |
| Sex: Female, Male Female | 1 Participants | 2 Participants | 3 Participants |
| Sex: Female, Male Male | 2 Participants | 2 Participants | 4 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 3 | 0 / 4 |
| other Total, other adverse events | 0 / 3 | 0 / 4 |
| serious Total, serious adverse events | 0 / 3 | 0 / 4 |
Outcome results
Primary
Change in Fecal Microbiome Diversity, Assessed by Bray-Curtis Index Comparing Those Who Received Acid Suppression Medications to Those Who Received Lifestyle Modifications
Time frame: From week 12 to week 4
Population: Zero participants analyzed as only 1 participant completed. Data was not analyzed and is not included here to protect the confidentiality of this one participant.
Secondary
Percent Subjects Eating High Fiber Diet
At each study visit, we will assess the effects of longterm diet on the microbiome by using the Harvard-Willett Food Frequency Questionnaire. Using this data, we will classify each subject as low vs high fiber.
Time frame: Up to Week 64
Population: Zero participants analyzed as only 1 participant completed. Data was not analyzed and is not included here to protect the confidentiality of this one participant.