Diverticulosis, ColonicNCT00663247
Mechanistic Randomized Controlled Trial (RCT) of Mesalazine in Symptomatic Diverticular Disease
A study testing Mesalazine in people with Diverticulosis, Colonic, run by University of Nottingham at 1 site in United Kingdom.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 85 years
- Conditions the study is for
- Diverticulosis, Colonic
- What is being tested?
- Mesalazine
- Type of treatment
- Medical device
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 40 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- Apr 2008to Jan 2011
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 85 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country.
United Kingdom1 site
NIHR Biomedical Research Unit, Nottingham University Hospital
Nottingham, Nottinghamshire, NG7 2UH
About this study
Official title: Mechanistic Randomized Controlled Trial of Mesalazine in Symptomatic Diverticular Disease
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.
Read the 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.
- Conditions
- Diverticulosis, Colonic
- Being tested
- Mesalazine, Placebo
- Keywords
- Diverticular disease, Inflammation, Mesalazine
- Medical subject headings
- Diverticulosis, Colonic, Diverticular Diseases, Inflammation
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MesalazineDevice
Also called Salofalk®, 5 ASA
3 grams daily for 3 months
PlaceboDrug
Also called Sham medication
3 grams daily for 3 months
| Study group | Role | What they receive |
|---|---|---|
| B | Placebo comparator | placebo used as control for comparison with active drug Receives: Drug: Placebo |
| A | Active comparator | Not described Receives: Device: Mesalazine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Difference in galanin expression in mucosal nerves from 0 to 12 weeks
Measured: 12 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Apr 2008 (estimated)
- Study startApr 2008
- Primary completionJan 2011
- Study completionJan 2011
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Diverticulosis, ColonicStudies of the same condition, open and under way.
- More trials run by University of NottinghamThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 40 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Nottingham
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- RC Spiller, Prof, Principal investigator, Nottingham University Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00663247
- Sponsor's protocol ID
- 07057
- Status last verified
- Jun 2012
- First submitted
- 18 Apr 2008
- Last updated
- 14 Jun 2012
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 14 Jun 2012. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Mechanistic Randomized Controlled Trial of Mesalazine in Symptomatic Diverticular Disease
- ClinicalTrials.gov ID
- NCT00663247
- Acronym / sponsor ID
- 07057
- Conditions
- Diverticulosis, Colonic
- Keywords
- Diverticular disease, Inflammation, Mesalazine
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 40 participants (actual)
- Lead sponsor
- University of NottinghamUniversity, hospital or other
- Study start
- Apr 2008
- Primary completion
- Jan 2011 (actual)
- Study completion
- Jan 2011 (actual)
- First posted
- 22 Apr 2008 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| B | Placebo comparator | Drug: Placeboplacebo used as control for comparison with active drug |
| A | Active comparator | Device: Mesalazine |
Who may qualify
- Ages
- 18 to 85 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- 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
Key exclusion criteria (6 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| MesalazineAlso: Salofalk®, 5 ASA3 grams daily for 3 months | Device | A |
| PlaceboAlso: Sham medication3 grams daily for 3 months | Drug | B |
Primary outcome
Difference in galanin expression in mucosal nerves from 0 to 12 weeks
Time frame: 12 weeks
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Jun 2012.
Related trials for Diverticulosis, Colonic
Not yet recruitingObservational study
Analysis of the Role of the Microbiota in Diverticular Disease
Diverticular Disease of Colon, Acute Diverticulitis
RecruitingObservational study
Advanced Endo-therapeutic Procedure : Registry-based Observational Study
Zenker Diverticulum, Polyp of Colon
RecruitingObservational study
Quality of Life and Surgery in Diverticular Disease
Diverticulitis Colon, Quality of Life
RecruitingObservational study
Single-Stapled Technique for Colorectal Anastomosis
Colorectal Cancer, Colorectal Anastomosis
Active, not recruitingObservational study
The Diverticulitis Study
Colonic Diverticulitis, Colorectal Cancer
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
RC Spiller, Prof principal investigator
Nottingham University Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Mesalazine in people with Diverticulosis, Colonic, run by University of Nottingham at 1 site in United Kingdom.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 14 Jun 2012. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Difference in galanin expression in mucosal nerves from 0 to 12 weeks (time frame: 12 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Jun 2012.