Advanced Metagenomic Analysis of Human Colonic Microbiota in Patients With Chronic GI Disorders

NCT01099111 | Completed Results DMC

• 2 other identifiers: 09 -116243 - 29 - AT
• Study Type: observational
• Target: 225
• Locations: 1 country
• Sites: 1

Brief Summary

This clinical trial hypothesize that Gut Microbiota (bacteria, viruses, fungi)play a major role in the occurrence and progression of many chronic gastrointestinal diseases like Irritable Bowel Syndrome, Inflammatory Bowel Diseases and Colo-Rectal Cancer. Hence, aims to study the spectrum of such microbiota in these patients as compared to normal subjects, by utilizing metagenomic techniques rather than cultural methods.

Conditions

Irritable Bowel Syndrome; Colitis, Ulcerative; Crohn Disease; Colonic Neoplasms

Keywords

IBS; UC; CD; CRAP/CRC

Outcome Measures

Primary Outcomes (1)

• Colonic-Mucosa Associated Microbial Species Per Compiled Participants in 5 Different Arms

  The entire mucosal microbial community were profiled using high-throughput DNA sequencing and microarray technology. The microarray approach is based on 16S rRNA gene targeted oligonucleotide allowing the rapid detection of thousands of DNA sequences simultaneously and thus constitutes an ideal tool to generate a comprehensive and holistic view of the gut microbial community in all participants of all study arms. Then they will be analysed between different colonic segments in each participant, pooled results of participants in each of the 5 arms will be compared to the measurable outcomes of other arms in general.

  1 - 2 weeks

Study Arms (5)

Irritable Bowel Syndrome

only one Colonoscopy with mucosal washing samples collection at the time of recruitment

Ulcerative Colitis

only one Colonoscopy with mucosal washing samples collection at the time of recruitment

Crohn's Disease

only one Colonoscopy with mucosal washing samples collection at the time of recruitment

Colo Rectal Cancer

only one Colonoscopy with mucosal washing samples collection at the time of recruitment

Control: Normal Subjects

only one Colonoscopy with mucosal washing samples collection at the time of recruitment

Eligibility Criteria

• Age: 16 Years - 70 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

We propose to recruit our cohort of patients from the King Fahad Medical City in Riyadh (largest tertiary care hospital of Saudi MOH with wide open referral system), over one year between July 2010 and July of 2011. Fifty participants with each of the focus conditions (IBS, UC, CD, CRC) will be compared to fifty participants with no GI complaints and have a normal colonic mucosa (by endoscopic and histological examination).

You may qualify if:

• IBS: 50 consecutive patients presenting to KFMC GI service after launching the project on July 2010, will be recruited if they meet the following conditions:
• Meet the diagnostic criteria as per ROME-II classification and as judged by experienced consultants for not less than 5 years.
• IBS with diarrhea or constipation or mixed predominance pattern will be included.
• Standard diagnostic tests have to be done to exclude any possible organic lesion to explain the abdominal pain, and all have to be negative.
• IBD: from the KFMC GI service database, 50 Ulcerative Colitis (UC) and 50 Crohn's Disease (CD) will be selected according to following:
• Confirmed diagnosis as CD or UC based on clinical, endoscopic and histological criteria.
• Specifically did not use antibiotics for last 6 months before enrollment.
• Detailed information about current treatment regimen has to be provided, and current use of 5-ASA, Steroid or Azathioprine will not hold from enrolling the patients as we cannot have patients off any one or more of these medications. (Obviously, we cannot exclude effects of these medications on microbiota, but it is not the focus of the current study).
• None of the patients selected would be on anti-TNF medications.
• CRC: 50 consecutive cases of confirmed CRC as per histological diagnosis made by 2 experienced pathologists will be included. Feasibility to do full colonoscopy before any surgical resection would be a condition to recruit any patient.
• Normal Subjects: 50 normal control groups that are matched for age and sex to the other 3 disease groups will be selected from consecutive CRC screening colonoscopy subjects who get referred to KFMC GI service during the study period, and proved to have no GI disorders. 25 will be selected from Urban and 25 from Rural areas of KSA.

You may not qualify if:

• Treatment with antibiotics for the last 6 months before enrollment.
• Absence of recent infective colitis, bowel obstruction, or colonic/small intestinal resection surgery.
• Not on any medication that may affect gut microbiota, like: cholestyramine, ursodeoxycholic acid, gut prokinetic agents.
• Refusal to comply with the unified bowel preparation instructions for all cases.

Sponsors & Collaborators

• King Fahad Medical City: lead
• King AbdulAziz City for Science and Technology: collaborator

Study Sites (1)

KFMC

Riyadh, Riyadh Region, 11525, Saudi Arabia

Location

Biospecimen

Retention: SAMPLES WITH DNA

Colonic washing samples from 4 specific segments (cecum, transverse, proximal sigmoid and rectum) of every subject will be retained for 16S rRNA analysis for the study purpose, and more samples will be retained for further analysis later on. Samples from the unified colonic segments (each collected as 15 cc in each of four 20 cc tubes and stored in -70 Freezer) were completely recruited from 50 normal subjects, 50 IBS, 50 UC, 46 CD and only 29 CRC. One to two tubes from each segment sample of all subjects have been utilized for DNA extraction and accepted if identified sufficient according to lab. Hence submitted for 16S rRNA analysis. Currently we are waiting for intra-cohort comparison of samples, then inter-cohort comparisons among different study groups will be done.

MeSH Terms

Conditions

Irritable Bowel Syndrome; Colitis, Ulcerative; Crohn Disease; Colonic Neoplasms

Condition Hierarchy (Ancestors)

Colonic Diseases, Functional; Colonic Diseases; Intestinal Diseases; Gastrointestinal Diseases; Digestive System Diseases; Colitis; Gastroenteritis; Inflammatory Bowel Diseases; Colorectal Neoplasms; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms

Limitations and Caveats

After completing recruitment, the colonic mucosal washing sampling did not result in enough DNA extract and we had to drop some of the participants for analysis.

Results Point of Contact

• Title: Dr. Ahmed Al Omair
• Organization: KFMC

aalomair@kfmc.med.sa

+96612889999

Study Officials

• Ahmed O AlOmair, MD

  KFMC

  PRINCIPAL INVESTIGATOR

• Ali Al Shanqeeti, MD

  KACST

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: CROSS SECTIONAL
• Sponsor Type: OTHER GOV
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Head, GI section + GI Consultant

Study Record Dates

• First Submitted: April 1, 2010
• First Posted: April 6, 2010
• Study Start: July 1, 2010
• Primary Completion: January 1, 2012
• Study Completion: March 1, 2012
• Last Updated: May 22, 2014
• Results First Posted: May 22, 2014

Record last verified: 2014-04

Locations

SA (1)