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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
University of Nottingham
ClinicalTrials.gov Identifier:
NCT00663247
First received: April 18, 2008
Last updated: June 13, 2012
Last verified: June 2012
  Purpose

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 Intervention
Diverticulosis, Colonic
Device: Mesalazine
Drug: Placebo

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Mechanistic Randomized Controlled Trial of Mesalazine in Symptomatic Diverticular Disease

Resource links provided by NLM:


Further study details as provided by University of Nottingham:

Primary Outcome Measures:
  • Difference in galanin expression in mucosal nerves from 0 to 12 weeks [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]

Enrollment: 40
Study Start Date: April 2008
Study Completion Date: January 2011
Primary Completion Date: January 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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.

  Eligibility

Ages Eligible for Study:   18 Years to 85 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00663247

Locations
United Kingdom
NIHR Biomedical Research Unit, Nottingham University Hospital
Nottingham, Nottinghamshire, United Kingdom, NG7 2UH
Sponsors and Collaborators
University of Nottingham
Investigators
Principal Investigator: RC Spiller, Prof Nottingham University Hospital
  More Information

No publications provided

Responsible Party: University of Nottingham
ClinicalTrials.gov Identifier: NCT00663247     History of Changes
Other Study ID Numbers: 07057
Study First Received: April 18, 2008
Last Updated: June 13, 2012
Health Authority: United Kingdom: Medicines and Healthcare Products Regulatory Agency

Keywords provided by University of Nottingham:
Diverticular disease
Inflammation
Mesalazine

Additional relevant MeSH terms:
Diverticulosis, Colonic
Diverticulum
Colonic Diseases
Digestive System Diseases
Gastrointestinal Diseases
Intestinal Diseases
Pathological Conditions, Anatomical
Mesalamine
Analgesics
Analgesics, Non-Narcotic
Anti-Inflammatory Agents
Anti-Inflammatory Agents, Non-Steroidal
Antirheumatic Agents
Central Nervous System Agents
Peripheral Nervous System Agents
Pharmacologic Actions
Physiological Effects of Drugs
Sensory System Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on October 23, 2014