Clinical trial NCT01493349: Pathophysiology of Diverticular Disease
Official title: The Role of Intestinal Microbiota Composition and Intestinal Permeability in the Development of (Complicated) Diverticular Disease.
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Colonic Diverticula
Diverticulitis
Keywords: Colonic diverticula
Diverticulitis
Lead sponsor: Maastricht University Medical Center
Sponsor class: OTHER
First posted: 2011-12-16
Enrollment: 210
Sex: ALL
Minimum age (years): 50
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Time perspective: CROSS_SECTIONAL
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients referred to the hospital by their general practitioner

Brief summary: Colonic diverticular disease is a highly prevalent condition in Western populations. The prevalence increases age-dependently from 5% at 40 years to 65% by the age of 85 years (1-3). The majority remain asymptomatic. However, a significant proportion of the patient population develops complications, such as diverticulitis with or without symptoms (10-20%) (1, 4-10). Perforated diverticulitis is rare with an estimated incidence of 4 per 100.000 per year, but the associated mortality rate is 22% to 39% (9, 11, 12). In the United States, the complications related to diverticular disease account for 130.000 hospitalizations each year, resulting in substantial health care costs (13). In Europe, it is estimated that approximately 23.600 deaths per year can be attributed to complicated diverticular disease, and the mortality will probably increase in the future due to the aging population (15-17). Several case studies report an overall increase in the incidence of diverticulitis, based on the increase in hospitalizations (18). Kang et al, reported a 16% increased male admission rate and 12% female admission rate for diverticulitis, between 1989/1990 and 1999/2000 (19). Aging and the Western diet, low in fiber and high in fat, in combination with increased intraluminal pressure and alterations in colonic motility are considered important etiological factors. A disturbance in large bowel motility is suggested to be a common pathophysiological feature in IBS and diverticular disease (20, 21). Based on observations that IBD, subgroups of IBS and (symptomatic) diverticular disease share clinical symptoms, the hypothesis is derived that they might also share pathophysiological factors like low grade inflammation, changed microbiota composition and activity, and increased intestinal permeability. The identification of clinical and pathophysiological factors associated with an increased risk for complicated diverticular disease may help to identify patients with diverticular disease, prevent complications, develop strategies to improve quality of life and reduce the related health care costs. Therefore we aim to investigate the composition of luminal and mucosal intestinal microbiota and the intestinal permeability in the development of diverticular disease and complicated diverticular disease. We hypothesize that both the intestinal microbiota and intestinal permeability are altered in patients with (current- or previous history of complicated) diverticular disease.


Eligibility criteria: Inclusion Criteria:

* Age ≥ 50 years and ≤ 75 years
* Scheduled for colonoscopy
* Written informed consent
* Patient group: The presence of diverticulosis, diagnosed during the scheduled colonoscopy
* Control group: During the scheduled colonoscopy, diverticulosis or other
* gastrointestinal and liver diseases are absent. In other words, the
* colonoscopy is qualified as a 'normal' colonoscopy.

Exclusion Criteria:

* Age \< 18 years
* Presence of gastrointestinal and liver diseases, such as inflammatory bowel disease.
* Use of NSAID's and proton pump inhibitors, during the 5-day time period prior to endoscopy.
* Alcohol intake above 14 consumptions per week for males and 7 consumption per week for females
* (Sub)total colectomy or hemicolectomy.
* Refusal to participate in this study

Primary outcomes:
measure: intestinal (luminal and mucosal) microbiota composition
timeFrame: up to 2 years
Secondary outcomes:
measure: Expression of tight junction proteins
timeFrame: up to 2 years
measure: Intestinal permeability
timeFrame: up to 2 years
Other outcomes:
Locations:
city: Maastricht
country: Netherlands
facility: Maastricht University Medical Center
state: Limburg
Study officials:
affiliation: Maastricht University Medical Center
name: A. M. Masclee, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Maastricht University Medical Center
name: D. Jonkers, PhD
role: STUDY_CHAIR
affiliation: Maastricht University Medical Center
name: R. C. Deutz, MD
role: STUDY_CHAIR
References: