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Mechanistic Randomized Controlled Trial (RCT) of Mesalazine in Symptomatic Diverticular Disease

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. Read our disclaimer for details. Identifier: NCT00663247
Recruitment Status : Completed
First Posted : April 22, 2008
Last Update Posted : June 14, 2012
Information provided by (Responsible Party):
University of Nottingham

Brief Summary:
Diverticulosis (bulges in the bowel wall) affects two third of the elderly population in the UK. Diverticular disease and its complications are responsible for 68000 hospital admissions and 2000 deaths per year. It commonly produces recurrent short lived abdominal pain, changes in bowel habit and incontinence. The causes of symptoms are not known and the treatments unsatisfactory. Recent studies have found an association between inflammation, alteration of bowel nerves and symptoms. Mesalazine is an anti-inflammatory drug used in inflammatory bowel conditions, such as ulcerative colitis and crohn's disease. We plan to perform a randomized double blind (neither the patients or the doctors known which treatment the patient is taking) placebo (sham medication) controlled trial of mesalazine in symptomatic diverticular disease patients. We anticipate a reduction in the amount of inflammation, bowel nerve changes and symptoms in patients taking mesalazine compare to those taking the placebo.

Condition or disease Intervention/treatment Phase
Diverticulosis, Colonic Device: Mesalazine Drug: Placebo Not Applicable

Detailed Description:

Diverticular disease affects two thirds of the elderly population in the United Kingdom. Only a small fraction of individuals with diverticulosis develop symptoms, perhaps 1 in 10, for reasons which are not well understood. The symptoms however are quite disabling as we found in a recent survey which indicated that around 36% suffered recurrent abdominal pain. Surprisingly, given the severity of the disability there has been very little research into the factors predicting the development of painful diverticular disease. Recent studies have indicated however that there may be an inflammatory component since the best predictor of recurrent abdominal pain is a previous episode of acute diverticulitis.

Just what initiates an attack of acute diverticulitis is poorly understood but may include the inspissation of fecal material in the diverticulum which then leads to pressure on the lining epithelium and a break down of barrier function. This allows colonic bacteria to enter the lamina propria where they cause acute inflammation, attracting pus cells from the circulating blood and creating micro-abscesses. The resolution of this involves fibrosis and scaring together with muscular hypertrophy which may well lead to secondary motor abnormalities. Patients with symptomatic diverticular disease are known to have higher intraluminal pressures, both at baseline and in response to stimuli such as a meal or prostigmine.

A recent report in which patients admitted with acute diverticulitis were followed for two years found that a very high proportion of such individuals subsequently develop recurrent chronic abdominal pain. Recent work has indicated that this leaves a permanent change in mucosal innervation. Markers of nerve injury including galanin and substance P are upregulated in patients with symptoms as opposed to those without. This is the first time that an objective marker has been shown to distinguish patients on the basis of symptoms.

While acute diverticulitis may be the initiating insult, a chronic low level inflammation may also be required to maintain visceral hypersensitivity. Where detailed quantitative histology has been performed in diverticular disease, some individuals have been identified with a lymphocytic infiltration. In other circumstances, chronic inflammation sensitises mucosal nerves and is associated with visceral hypersensitivity, something which has also been noted in symptomatic diverticular disease.

Whether anti-inflammatory agents could reverse this process is as yet unknown but there are currently available safe and effective treatments for inflammatory bowel disease such as 5 amino-salicylic acid or budesonide which might well be effective and allow further evaluation of the role of low grade inflammation in symptomatic diverticular disease.

This study aims to investigate the inflammatory, neurological and symptomatic effects of mesalazine in diverticular disease.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 40 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Mechanistic Randomized Controlled Trial of Mesalazine in Symptomatic Diverticular Disease
Study Start Date : April 2008
Actual Primary Completion Date : January 2011
Actual Study Completion Date : January 2011

Resource links provided by the National Library of Medicine

Arm Intervention/treatment
Placebo Comparator: B
placebo used as control for comparison with active drug
Drug: Placebo
3 grams daily for 3 months
Other Name: Sham medication

Active Comparator: A Device: Mesalazine
3 grams daily for 3 months
Other Names:
  • Salofalk®
  • 5 ASA

Primary Outcome Measures :
  1. Difference in galanin expression in mucosal nerves from 0 to 12 weeks [ Time Frame: 12 weeks ]

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 85 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Symptomatic diverticular disease with short lived recurrent abdominal pain on 3 or more days a month.
  • 18 - 85 years of age.
  • Signed informed consent
  • Presence of at least one diverticulum in the left colon

Exclusion Criteria:

  • Pregnant or lactating women.
  • Severe co-morbidity, alcoholism or drug dependence or inability to give informed consent.
  • Contraindications to use of Mesalazine as detailed in SmPC.
  • Inability to stop NSAIDs (non-steroidal anti-inflammatory agents) or long term antibiotics.
  • The use of specific concomitant medications as detailed in the section below.
  • Presence of other gastrointestinal inflammatory conditions such as ulcerative colitis, Crohn's disease and Coeliac disease.

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): NCT00663247

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United Kingdom
NIHR Biomedical Research Unit, Nottingham University Hospital
Nottingham, Nottinghamshire, United Kingdom, NG7 2UH
Sponsors and Collaborators
University of Nottingham
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Principal Investigator: RC Spiller, Prof Nottingham University Hospital
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Responsible Party: University of Nottingham Identifier: NCT00663247    
Other Study ID Numbers: 07057
First Posted: April 22, 2008    Key Record Dates
Last Update Posted: June 14, 2012
Last Verified: June 2012
Keywords provided by University of Nottingham:
Diverticular disease
Additional relevant MeSH terms:
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Diverticular Diseases
Diverticulosis, Colonic
Intraabdominal Infections
Gastrointestinal Diseases
Digestive System Diseases
Pathological Conditions, Anatomical
Colonic Diseases
Intestinal Diseases
Anti-Inflammatory Agents, Non-Steroidal
Analgesics, Non-Narcotic
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Anti-Inflammatory Agents
Antirheumatic Agents