The Gut Microbiome in Diverticulitis and Diverticulosis

NCT02221713 | Withdrawn

• 1 other identifier: IRAS 163084
• Study Type: observational
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

Colonic diverticula are outpouchings of the large bowel, and they occur in up to 60% of people over 60 years of age. About 10-25% of patients with diverticula will have symptoms. These can range from acute diverticulitis, which can be a lethal infection to symptomatic diverticular disease, which involves inflammation of the bowel and altered bowel habits, decreasing patients' quality of life. We do not know which patients will develop acute diverticulitis or which patients will develop diverticula in their colon. We believe that diverticulitis may be associated with, or even caused by, alterations in the bacteria that live in the colon, known as the gut microbiome. Until recently it was too expensive and too complex to examine the microbiome in detail. We propose to examine for the first time in detail the microbiome of patients with acute diverticulitis and asymptomatic diverticulosis. Stool samples will be analysed for gut microbiome composition by 16S ribosomal RNA gene pyrosequencing. There is a part of the bacterial cell, the ribosome, which is the same in all bacteria (16S). Through PCR, polymerase chain reaction, and sequencing, we can separate out the different types of bacteria in a sample. We can then look at the different kinds of bacteria in each patient population, as well as how diverse the populations are within the groups, and compared to other groups. We hope to be able to discriminate between the microbiome of patients with acute diverticulitis and asymptomatic diverticulosis. This study many change how diverticulitis and diverticulosis are conceptualized and treated. Alterations in the microbiome in these disease states may be able to be treated, preventing further disease.

Conditions

Diverticulitis; Diverticulosis; Diverticular Disease

Keywords

diverticulitis; diverticulosis; diverticular disease

Outcome Measures

Primary Outcomes (1)

• assessment of gut microbiome

  Patients will give stool specimen or rectal swab after enrolling in the study. Stool samples will undergo 16S rRNA pyrosequencing for microbiome analysis.

  at time of enrollment

Study Arms (4)

Group A: perforated diverticulitis

Patients with acute diverticulitis will be recruited from the A\&E department at King's, prior to commencement of antibiotics. Rectal swabs will be obtained from patients with a chief complaint of acute abdominal pain upon initial assessment, prior to initial antibiotics. All specimens will be initially frozen, but only patients specimens with an admitting diagnosis of acute diverticulitis and colonic imaging (CT imaging or visualization at surgery) will be analysed. This group will include patients with perforated diverticulitis (i.e., Hinchey III or IV).

Group B: unperforated diverticulitis

Patients with acute diverticulitis will be recruited from the A\&E department at King's, prior to commencement of antibiotics. Rectal swabs will be obtained from patients with a chief complaint of acute abdominal pain upon initial assessment, prior to initial antibiotics. All specimens will be initially frozen, but only patients specimens with an admitting diagnosis of acute diverticulitis and colonic imaging (CT imaging or visualization at surgery) will be analysed. This group will include patients with unperforated diverticulitis (Hinchey I or II).

Group C: asymptomatic diverticulosis

Patients with asymptomatic diverticulosis will be recruited from the 2-week wait (2ww) colorectal cancer pathway. Patients presenting with a chief complaint of fresh PR bleeding, with no other complaints, will be recruited prior to diagnostic imaging, either by CT, CT colonography, or endoscopy. They will provide a stool sample or rectal swab prior to bowel cleansing, if required for their evaluation, as that may alter the microbiome. Those patient samples with diverticulosis (and or haemorrhoids, as the other most common cause of fresh PR bleeding) will be analysed.

Group D: normal controls

Patients with or without haemorrhoids, and no other colonic pathology will be recruited from the 2ww colorectal cancer pathway. These will be the normal controls. Patients presenting with a chief complaint of fresh PR bleeding, with no other complaints, will be recruited prior to diagnostic imaging, either by CT, CT colonography, or endoscopy. They will provide a stool sample or rectal swab prior to bowel cleansing, if required for their evaluation, as that may alter the microbiome. Those patient samples with diverticulosis (and or haemorrhoids, as the other most common cause of fresh PR bleeding) will be analysed.

Eligibility Criteria

• Age: 18 Years - 90 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Groups A and B. Patients with acute diverticulitis will be recruited from A\&E at King's College Hospital. If they agree to participate, we will request either a stool sample to be produced, or, if that is not feasible, then a member of the study team will procure a rectal swab. Those patients with Hinchey III or IV's specimens will be assessed in Group A, while those patients with Hinchey I or II will be assessed in Group B. Groups C and D. Patients referred through the Two Week Wait (2ww) Colorectal Cancer pathway who are both at low risk for colorectal cancer and have low levels of anxiety, both as assessed by a physician outside the study team will be approached to participate. These patients will be able to produce the stool sample prior to presenting for flexible sigmoidoscopy as a part of their workup.

You may qualify if:

• Groups A and B. Patients with acute diverticulitis - patients presenting to A\&E at King's College Hospital with new onset abdominal pain, with or without a known diagnosis of diverticulitis
• Groups C and D. Patients with asymptomatic diverticulosis and normal controls
• \- Patients being assessed through the 2ww Colorectal Cancer pathway with a chief complaint of fresh PR bleeding and no other 'red flag' symptoms, who are not overly anxious over their diagnosis as assessed by a physician outside the study team.

You may not qualify if:

• Groups A and B. Patients with acute diverticulitis
• Patients in extremis- e.g. systolic blood pressure less than 80 on arrival or pulse greater than 115
• Patients who have received antibiotics in the three months prior to presentation.
• Vulnerable patient populations
• Groups C and D. Patients with asymptomatic diverticulosis and normal controls
• Patients with high levels of pre-test anxiety, as determined by their assessing physician, outside the study team
• Vulnerable patient populations

Sponsors & Collaborators

• King's College Hospital NHS Trust: lead

Study Sites (1)

King's College Hospital

London, se59rs, United Kingdom

Location

Biospecimen

Retention: SAMPLES WITH DNA

stool samples and rectal swabs of stool

MeSH Terms

Conditions

Diverticulitis; Diverticulum; Diverticular Diseases

Condition Hierarchy (Ancestors)

Gastroenteritis; Gastrointestinal Diseases; Digestive System Diseases; Pathological Conditions, Anatomical; Pathological Conditions, Signs and Symptoms

Study Officials

• Ingvar Bjarnason, MD, MSc FRCPath, FRCP(Glasg)

  King's College Hospital NHS Trust

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: FAMILY BASED
• Time Perspective: CROSS SECTIONAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 19, 2014
• First Posted: August 20, 2014
• Study Start: June 1, 2020
• Primary Completion: April 1, 2021
• Study Completion: May 1, 2021
• Last Updated: April 2, 2020

Record last verified: 2020-03

Locations

GB (1)