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Completed

NCT Number: NCT02872961

SIBO, Immune Activation, and FGIDs in Children

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.

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Key information

Conditions

Small Intestinal Bacterial Overgrowth Colonic Diseases Colonic Diseases, Functional Digestive System Diseases Functional Abdominal Pain Functional Dyspepsia Gastrointestinal Diseases Intestinal Diseases Irritable Bowel Syndrome

Age range

4 year–17 year

Sex eligibility

All sexes

Study type

Observational

Primary location

The University of Texas of Health Science Center at Houston

Houston, Texas, 77030, United States

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Pediatric patient, aged 4-17 years, upon initial evaluation for abdominal pain.
  • Complaints of abdominal pain for at least 2 months upon entry into the study.
  • Esophagogastroduodenoscopy (EGD) ordered by the patient's gastroenterologist for further evaluation / work-up of the patient's abdominal pain.
  • 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).
  • 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.

  • Evidence of enteric infection or infestation on laboratory screening or on mucosal biopsy.
  • Known or suspected of liver, renal, or pancreatic disease. 6. Diabetes mellitus, systemic lupus erythematosus, and/or other systemic disease.
  • 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.
  • 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.
  • 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.
  • Symptomatic from an atopic disorder (i.e., eczema, allergic rhinitis, asthma) within the 2 weeks preceding serum collection for the study.
  • 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.
  • Cancellation of the endoscopy procedure by the subject's gastroenterologist, parent, and/ or legal guardian.

Treatment and study plan

Primary outcomes

  1. Abdominal Pain Index

    Time frame: Baseline

    To further evaluate symptom severity, on the day of endoscopic evaluation, each subject (or the legal guardian, when appropriate) will be asked to complete the Abdominal Pain Index, which is comprised of five items assessing the frequency, duration, and intensity of abdominal pain episodes the subject has experienced during the previous two weeks. This index was previously validated as a clinical measure of abdominal pain in pediatric patients. Responses to the five pain ratings are standardized, and the Z-scores are averaged to yield an index of abdominal pain.

Secondary outcomes

  1. Duodenal fluid microbiota

    Time frame: Baseline

    Small bowel aspirate specimens of 10 patients from each group (20 total samples) will be randomly selected for further analysis. The tubes will be batched, and the preserved samples will be processed (via microbial DNA extraction, followed by bacterial 16S rRNA gene amplification via PCR), after which deep pyrosequencing analysis of the PCR-amplified 16S rRNA genes will be performed. Pyrosequencing data is processed using the Ribosomal Database Project (RDP) pyrosequencing pipeline (http://pyro.cme.msu.edu/). Statistical differences in the diversity and phylogenetic composition of bacteria in the specimens will be assessed by using the online analysis tools at the RDP pyrosequencing pipeline website and by using both the standard and quantitative UniFrac analyses.

  2. Serum biomarker levels

    Time frame: Baseline

    Levels of key circulating gut biomarkers of inflammation will be measured in serum samples; specifically, levels of IL-1-β, IL-6, IL-8, IL-10, IL-12p70, IFN-γ,TNF-α, and osteoprotegerin), intestinal barrier function (TIMP-1), and GI motility (BDNF) will be measured.

  3. Duodenal tissue inflammatory cell infiltration

    Time frame: Baseline

    Mucosal immune cells from duodenal biopsy specimens will be characterized using Giemsa staining for identification of mast cells and antibodies directed against CD4, CD8 (T-cell markers), and CD20 (B-cell marker) using accepted methods for immunohistochemistry. Quantification of immune cells will be performed on both the hematoxylin and eosin (e.g., total immune cells, lymphocytes, monocytes, eosinophils, basophils) and immunohistochemically stained sections (e.g., mast cells, T-lymphocytes, B-lymphocytes).

  4. Duodenal tissue toll-like receptor expression

    Time frame: Baseline

    Small intestinal toll-like receptor expression will be determined via immunohistochemical staining using established protocols. Levels of the following toll-like receptors will be checked: TLR-2, TLR-4, TLR-5, TLR-9 as these toll-like receptors recognize bacterial ligands and are elevated in inflammatory conditions.

  5. Duodenal tissue cytokine levels

    Time frame: Baseline

    The following cytokine levels will be measured in the small intestinal tissue lysate: Human IL-1-β, IL-6, IL-8, IL-10, IL-12p70, IFN-γ, and TNF-α.

  6. Wong-Baker FACES Pain Rating Scale

    Time frame: Baseline

    To further assess the subject's abdominal pain severity, on the day of endoscopic evaluation, each subject (or the legal guardian, when appropriate) will be asked to rate the subject's current pain, average pain over the preceding two weeks, and worst pain experienced during the preceding two weeks using the Wong-Baker FACES™ Pain Rating Scale. This scale has been validated for use in children and consists of faces showing varying degrees of discomfort, along with corresponding descriptions of the pain and numbers to rate pain.

Sponsors and collaborators

Lead sponsor

The University of Texas Health Science Center, Houston

Other

Registry information

Official study title

Relationship Between Small Intestinal Bacterial Overgrowth (SIBO) and Immune System Activation in Childhood Abdominal Pain-Related Functional Gastrointestinal Disorders (FGIDs)

Acronym: SIBO

Important dates

Study start
2013
Primary completion
2017
Study completion
2017
First posted
Aug 19, 2016
Registry last updated
Mar 29, 2021

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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