Functional Dyspepsia Microbiome Study

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT02340312
Recruitment Status : Recruiting
First Posted : January 16, 2015
Last Update Posted : January 16, 2015
University of Kansas
Information provided by (Responsible Party):
Craig A. Friesen, MD, Children's Mercy Hospital Kansas City

Brief Summary:
Recurrent abdominal pain has long been acknowledged to be the most common chronic pain entities in children. The purpose of this study is to describe the microbiome in children with FD and to explore relationships between the microbiome and postprandial distress syndrome, anxiety scores, and mucosal biomarkers or anxiety. The specific goals of this study are to: 1) Determine the frequencies and relative proportions for specific bacteria or bacteria phyla in children with FD in both duodenal mucosal specimens and stool samples. 2) Determine if the frequencies or proportions of specific bacteria or bacteria phyla differ between children with and without PDS. 3) Determine bi-variate correlations between bacteria/phyla frequency, bacteria/phyla proportions, anxiety scores, and mucosal biomarkers, respectively.

Condition or disease Intervention/treatment
Functional Dyspepsia Procedure: EGD Other: Collection of Stool Specimens

  Show Detailed Description

Study Type : Observational
Estimated Enrollment : 200 participants
Observational Model: Cohort
Time Perspective: Prospective
Official Title: Evaluation of the Duodenal Microbiome in Pediatric Functional Dyspepsia
Study Start Date : January 2015
Estimated Primary Completion Date : January 2020

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Indigestion

Intervention Details:
  • Procedure: EGD
    In this study patients are being scoped(EGD) as standard of care and being asked to allow .5 aggregate of tissue biopsy to be taken for research purposes.
  • Other: Collection of Stool Specimens
    We will be collecting stool samples from each participant for research purposes. Within two weeks after EGD tissue collection.

Primary Outcome Measures :
  1. Microbiome Analysis [ Time Frame: within 12 months from collection ]
    Fecal samples and 8 mucosal biopsies (descending duodenum) will be obtained from each subject. Samples will be processed and DNA isolated per standard lab techniques.16S rDNA sequence analysis of microbial communities within patient samples will be analyzed utilizing our HiSeq 1500 rapid run technologies. We will perform 2 X 150 bp paired end sequencing which will give exceptional coverage (reads > 30,000). We will sequence the V4 region of 16s RNA (E. coli 515-806), which is the method optimized for Illumina HiSeq 1500 currently. We will also sequence simultaneously the V3 region of 16s RNA to provide a dual-control analysis of samples. Confirmatory PCR will be employed when appropriate. Data will be reported as total counts for each identified bacterial species.

  2. Inflammatory Cell Density [ Time Frame: within 12 months from collection ]

    Routine histology slides previously stained with hematoxylin and eosin will be utilized for determination of eosinophil density.

    IHC techniques will be utilized for determination of mast cell density. Serial 3-μm paraffin sections will be air dried and heat fixed on slides. The sections will be deparaffinized with xylene and iodine and rehydrated in a graded series of alcohol. Utilizing tryptase monoclonal mouse antihuman mast cell tryptase antibody (clone AA1, Dako, Carpinteria, CA), sections will be stained on an automated Dako Autostainer 3400 using Dako's LSAB+ kit with streptoavidin conjugated to horseradish peroxidase.

    To determine density for each cell type, the entire specimen will be scanned to determine the subjective area of greatest involvement. Density will be determined by counting cells within 5 consecutive high-power fields (400X magnification). Peak and mean cell densities expressed as cells/hpf will be determined. This will be completed before study end.

  3. Immunohistochemistry (IHC) [ Time Frame: within 12 months from collection ]
    IHC staining will be performed and may include DCLK1, BDNF, TRPV1, and/or CRH-R1, respectively, depending on the results of an on-going pilot study. Staining intensity will be evaluated in a blinded fashion by a pathologist to assign scores for average IHC signal intensity (i.e. 0= none, 1= mild, 2= moderate, and 3= strong) as well as the percentage of tissue cells or fibers showing positive immunoreactivity. A sem-quantitative scoring system will be applied in which the final immunoreactive score will equal the product of the percentage of positive cells times the average staining intensity. Percentage of positive cells or fibers will be graded as follows: 0= negative-10%, 1= 11-33%, 2= 33-66%, and 3= > 67%. Immunoreactivity will be considered positive when the combined score ranges between 2-6 and negative with a score of 0-1. Other IHC stains may be performed should they become relevant as indicated by the literature. This will be performed before study end.

Secondary Outcome Measures :
  1. T-scores for the BASC will be collected as part of this study on the Data Collection Form. [ Time Frame: within 6 months from completion ]
    This information is used to assess psychosocial information from the patient.This will be collected and recorded before study end.

Biospecimen Retention:   Samples With DNA
Collection of .5 aggregate of doudenal tissue. Collection of stool samples.

Information from the National Library of Medicine

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Ages Eligible for Study:   8 Years to 17 Years   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population
Children and adolecents ages 8 to 17 inclusive that have been diagonsed with functional dyspepsia and are scheduled to have a EGD with biopsy.

Inclusion Criteria:

  • Diagnosis of FD as determined by the GI physician in accordance with Rome III criteria
  • Age 8-17 years inclusive
  • Scheduled for upper endoscopy as part of routine care after failing to respond to acid suppression therapy

Exclusion Criteria:

  • Use of oral antibiotic or probiotic within 8 weeks prior to enrollment
  • Use of systemic steroid or immunomodulating drug within 8 weeks of enrollment

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT02340312

Contact: Craig A Friesen, M.D. 816-983-6975
Contact: Trevor J Cole, B.S. 816-983-6025

United States, Missouri
The Children's Mercy Hospital Recruiting
Kansas City, Missouri, United States, 64108
Contact: Trevor J Cole, B.S.    816-983-6025   
Sponsors and Collaborators
Children's Mercy Hospital Kansas City
University of Kansas

Friesen CA, Schurman JV, Qadeer A, Andre L, Welchert E, Cocjin J. Relationship between mucosal eosinophils and anxiety in pediatric dyspepsia. Gastroenterology 2005; 129:A-158
Carpenter S. That gut feeling. Monitor on Psychol 2012; 43:51-55

Responsible Party: Craig A. Friesen, MD, M.D. Divison Cheif Gastroenterology, Children's Mercy Hospital Kansas City Identifier: NCT02340312     History of Changes
Other Study ID Numbers: 490390
First Posted: January 16, 2015    Key Record Dates
Last Update Posted: January 16, 2015
Last Verified: January 2015

Additional relevant MeSH terms:
Signs and Symptoms, Digestive
Signs and Symptoms
Gastrointestinal Diseases
Digestive System Diseases
Stomach Diseases