Mechanistic Randomized Controlled Trial (RCT) of Mesalazine in Symptomatic Diverticular Disease
Primary Purpose
Diverticulosis, Colonic
Status
Completed
Phase
Not Applicable
Locations
United Kingdom
Study Type
Interventional
Intervention
Mesalazine
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Diverticulosis, Colonic focused on measuring Diverticular disease, Inflammation, Mesalazine
Eligibility 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.
Sites / Locations
- NIHR Biomedical Research Unit, Nottingham University Hospital
Arms of the Study
Arm 1
Arm 2
Arm Type
Placebo Comparator
Active Comparator
Arm Label
B
A
Arm Description
placebo used as control for comparison with active drug
Outcomes
Primary Outcome Measures
Difference in galanin expression in mucosal nerves from 0 to 12 weeks
Secondary Outcome Measures
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT00663247
Brief Title
Mechanistic Randomized Controlled Trial (RCT) of Mesalazine in Symptomatic Diverticular Disease
Official Title
Mechanistic Randomized Controlled Trial of Mesalazine in Symptomatic Diverticular Disease
Study Type
Interventional
2. Study Status
Record Verification Date
June 2012
Overall Recruitment Status
Completed
Study Start Date
April 2008 (undefined)
Primary Completion Date
January 2011 (Actual)
Study Completion Date
January 2011 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of Nottingham
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
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.
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Diverticulosis, Colonic
Keywords
Diverticular disease, Inflammation, Mesalazine
7. Study Design
Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
40 (Actual)
8. Arms, Groups, and Interventions
Arm Title
B
Arm Type
Placebo Comparator
Arm Description
placebo used as control for comparison with active drug
Arm Title
A
Arm Type
Active Comparator
Intervention Type
Device
Intervention Name(s)
Mesalazine
Other Intervention Name(s)
Salofalk®, 5 ASA
Intervention Description
3 grams daily for 3 months
Intervention Type
Drug
Intervention Name(s)
Placebo
Other Intervention Name(s)
Sham medication
Intervention Description
3 grams daily for 3 months
Primary Outcome Measure Information:
Title
Difference in galanin expression in mucosal nerves from 0 to 12 weeks
Time Frame
12 weeks
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
85 Years
Accepts Healthy Volunteers
No
Eligibility 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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
RC Spiller, Prof
Organizational Affiliation
Nottingham University Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
NIHR Biomedical Research Unit, Nottingham University Hospital
City
Nottingham
State/Province
Nottinghamshire
ZIP/Postal Code
NG7 2UH
Country
United Kingdom
12. IPD Sharing Statement
Learn more about this trial
Mechanistic Randomized Controlled Trial (RCT) of Mesalazine in Symptomatic Diverticular Disease
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