Clinical trial NCT02872961: SIBO, Immune Activation, and FGIDs in Children
Official title: Relationship Between Small Intestinal Bacterial Overgrowth (SIBO) and Immune System Activation in Childhood Abdominal Pain-Related Functional Gastrointestinal Disorders (FGIDs)
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Small Intestinal Bacterial Overgrowth
Irritable Bowel Syndrome
Functional Dyspepsia
Functional Abdominal Pain
Lead sponsor: The University of Texas Health Science Center, Houston
Sponsor class: OTHER
First posted: 2016-08-19
Enrollment: 54
Sex: ALL
Minimum age (years): 4
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: no
Observational model: CASE_CONTROL
Time perspective: CROSS_SECTIONAL
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients (ages 4-17 years) presenting to the University of Texas-Houston Pediatric GI Clinic with complaints of abdominal pain and undergoing endoscopy (i.e., esophagogastroduodenoscopy \[EGD\] and possibly colonoscopy) for further evaluation (at the discretion of the patient's gastroenterologist) will be screened for inclusion into the study at the time that the endoscopic evaluation is ordered by the patient's gastroenterologist.

Brief summary: PURPOSE: This study will evaluate the relationships between small intestinal bacterial overgrowth (SIBO), immune activation, inflammation, and symptoms in pediatric abdominal pain-related functional gastrointestinal disorders (FGIDs), i.e., irritable bowel syndrome (IBS), functional dyspepsia (FD), \& functional abdominal pain (FAP), to better understand the role of SIBO in their pathogenesis. DESIGN \& PROCEDURES: Cross-sectional study. Subjects: Patients followed at the UT-Houston Pediatric GI clinic, aged 4-17 years, undergoing endoscopic evaluation of abdominal pain, meeting Rome III diagnostic criteria for IBS, FD, or FAP, without evidence of an organic etiology of abdominal pain upon routine laboratory, radiologic, endoscopic, histologic evaluation. Sample Size: At least 30 patients, ≥ 15 with SIBO (i.e., positive small bowel aspirate culture and/or glucose breath hydrogen test), and ≥15 without SIBO. Sample Materials: Small bowel biopsies and aspirates, serum, breath samples, symptom questionnaire responses. Measures: 1) Immune activation \& inflammation - measured by serum cytokine levels \& small intestinal tissue inflammatory cell infiltration \& cytokine levels. 2) Symptoms - measured by Abdominal Pain Index, Wong-Baker FACES™ Pain Rating Scale, Questionnaire on Pediatric Gastrointestinal Symptoms - Rome III Version. 3) Small bowel microbiota analysis - assessed by 454 pyrosequencing. RISKS \& POTENTIAL BENEFITS: Aside from the risks associated with routine endoscopy with biopsies, which would occur even without study enrollment, the risks associated with serum collection, one extra biopsy specimen collection, small bowel aspirate collection, completion of pain scales/ questionnaires, and the glucose breath hydrogen test for the purposes of the study are minimal. POTENTIAL IMPACT: This study should yield valuable information regarding the relationships between SIBO, immune activation, inflammation, and symptoms in pediatric IBS, FD, and FAP. Potential biomarkers to support the diagnosis of these FGIDs and novel targets for therapy, such as immune molecules and previously unrecognized bacterial phylotypes and species possibly contributing to disease pathogenesis, may be identified. Also, determining the reliability of the glucose breath hydrogen test vs. small bowel aspirate culture in the diagnosis of SIBO in this setting may enable the physician to avoid invasive and costly procedures in the diagnostic work-up of children with these FGIDs.


Eligibility criteria: Inclusion Criteria:

1. Pediatric patient, aged 4-17 years, upon initial evaluation for abdominal pain.
2. Complaints of abdominal pain for at least 2 months upon entry into the study.
3. Esophagogastroduodenoscopy (EGD) ordered by the patient's gastroenterologist for further evaluation / work-up of the patient's abdominal pain.
4. Fulfillment of Rome III criteria for the child/adolescent abdominal pain-related functional gastrointestinal disorders under study (i.e., irritable bowel syndrome, functional dyspepsia, and functional abdominal pain).
5. Signed informed consent for the subject's participation in the study provided by the parent / legal guardian; signed assent signed by study participants 8 years and older.

Exclusion Criteria:

History of short bowel syndrome, defined as clinically significant malabsorption resulting from surgical resection of a substantial portion (≥ 50%) of small intestine, or from complete dysfunction of an extensive portion (≥ 50%) of small bowel. 2. History of other gastrointestinal surgery (except for appendectomy). 3. Other known or suspected motility disorder such as achalasia, gastroparesis, chronic intestinal pseudo-obstruction, dumping syndrome, Hirschprung's disease, or neuromuscular disease.

4. Evidence of enteric infection or infestation on laboratory screening or on mucosal biopsy.

5. Known or suspected of liver, renal, or pancreatic disease. 6. Diabetes mellitus, systemic lupus erythematosus, and/or other systemic disease.

7. Use of antibiotics, mast cell stabilizers, leukotriene modifiers, and/or systemic steroids within 2 weeks preceding the small bowel aspirate culture and biopsies; use of antibiotics or probiotics within 2 weeks of the glucose breath hydrogen test.

8. Use of opiates or benzodiazepines (aside from any given for anesthesia purposes for the endoscopy procedure) or laxatives (aside from any given for bowel preparation for the endoscopy procedure) within 1 week preceding the small bowel aspirate culture and/ or glucose breath hydrogen test.

9. Acute infection or other acute inflammatory process (e.g., upper respiratory tract infection, pneumonia, urinary tract infection, gastroenteritis, pancreatitis, etc.) within the 2 weeks preceding the serum sample and mucosal biopsy collection.

10. Symptomatic from an atopic disorder (i.e., eczema, allergic rhinitis, asthma) within the 2 weeks preceding serum collection for the study.

11. Any evidence of inflammatory bowel disease, celiac disease, H. pylori infection, eosinophilic esophagitis, giardiasis, or other potential organic etiology of abdominal pain upon endoscopic / histologic evaluation.

12. Cancellation of the endoscopy procedure by the subject's gastroenterologist, parent, and/ or legal guardian.

Primary outcomes:
measure: Abdominal Pain Index
timeFrame: Baseline
Secondary outcomes:
measure: Duodenal fluid microbiota
timeFrame: Baseline
measure: Serum biomarker levels
timeFrame: Baseline
measure: Duodenal tissue inflammatory cell infiltration
timeFrame: Baseline
measure: Duodenal tissue toll-like receptor expression
timeFrame: Baseline
measure: Duodenal tissue cytokine levels
timeFrame: Baseline
measure: Wong-Baker FACES Pain Rating Scale
timeFrame: Baseline
Other outcomes:
Locations:
city: Houston
country: United States
facility: The University of Texas of Health Science Center at Houston
state: Texas
Study officials:
affiliation: The University of Texas of Health Science Center at Houston
name: Melissa R Van Arsdall, MD
role: PRINCIPAL_INVESTIGATOR
References: