Plain English Summary
Background and study aims
Diverticular disease affects two thirds of those over the age of 65 of whom about 1 in 5 will develop symptoms. These consist of abdominal pain and erratic bowel habit. There is as yet no effective treatment for these symptoms and this study aimed to test the idea that an anti-inflammatory drug called Mesalazine might benefit. Preliminary studies suggested possible benefit but this needed confirmation.
Who can participate?
Patients with known diverticular disease and recurrent abdominal pain and erratic bowel habit.
What does the study involve?
Patients were required to take either Mesalazine or dummy drug (placebo) twice daily for three months. At the beginning of the study, the lower bowel was examined and a small specimen taken from the lining. This was repeated at the end of the study to look at the effect of Mesalazine on the gut lining.
What are the possible benefits and risk?
We hoped that abdominal symptoms would improve. The drug has been used for many years and the side effects are well recognised. About 1 in 10 of the patients would not have tolerated the drug but only rarely (less than 1 time in 1000) would there have been serious side effects.
Where is the study run from?
Queens Medical Centre, Nottingham (UK)
When is the study starting?
August 2008 to January 2011
Who is funding the study?
The Wellcome Trust (UK)
Who is the main contact?
Dr Jan Smith
Jan.smith@nottingham.ac.uk
Trial website
Contact information
Type
Scientific
Primary contact
Prof Robin Spiller
ORCID ID
Contact details
Nottingham Digestive Disease Centre
C Floor South Block
Queen's Medical Centre
Derby Road
Nottingham
NG7 2UH
United Kingdom
+44 115 823 1090
robin.spiller@nottingham.ac.uk
Additional identifiers
EudraCT number
2006-006198-26
ClinicalTrials.gov number
NCT00663247
Protocol/serial number
29856; 086609
Study information
Scientific title
Mechanistic randomised controlled trial of mesalazine in symptomatic diverticular disease
Acronym
SAG44
Study hypothesis
To undertake a pilot mechanistic, two group parallel design, randomised controlled trial of anti-inflammatory treatment (mesalazine) in individuals with symptomatic diverticular disease to identify markers to assess the relationship between inflammation and symptoms.
Ethics approval
Nottingham Regional Ethics Committee 1, 12/10/2007, ref: 07/Q2403/83
Study design
Interventional two group parallel randomised double-blinded placebo controlled trial
Primary study design
Interventional
Secondary study design
Randomised controlled trial
Trial setting
Hospitals
Trial type
Treatment
Patient information sheet
Not available in web format, please use the contact details below to request a patient information sheet
Condition
Diverticular disease
Intervention
Mesalazine 3 g/day for 3 months
Placebo 3 g/day for 3 months
Total duration of follow-up is 3 months (12 weeks) in each study arm.
Intervention type
Drug
Phase
Phase IV
Drug names
Mesalazine
Primary outcome measure
Difference in change in galanin expression in mucosal nerves from 0 to 12 weeks/withdrawal between mesalazine and placebo treated groups.
Secondary outcome measures
Differences between mesalazine and placebo groups with respect of changes from 0 to 12 weeks/withdrawal of:
1. Substance P expression in mucosal nerves
2. Cell counts of CD3, CD25, CD68 positive cells, neutrophils and Paneth cells
3. Faecal calprotectin
4. Urine neopterin
5. Serum interleukin-8 (IL-8)/interleukin-6 (IL-6)
6. Abdominal pain, stool frequency amd mean stool consistency
7. Messenger ribonucleic acid (mRNA)/protein expression of inflammatory cytokines
Overall trial start date
01/08/2008
Overall trial end date
01/01/2011
Reason abandoned (if study stopped)
Eligibility
Participant inclusion criteria
1. Symptomatic diverticular disease with short lived recurrent abdominal pain on 3 or more days a month
2. Aged 18 - 85 years of age, either sex
3. Signed informed consent
4. Presence of at least one diverticulum in the left colon
Participant type
Patient
Age group
Adult
Gender
Both
Target number of participants
40
Participant exclusion criteria
1. Pregnant or lactating women
2. Severe co-morbidity, alcoholism or drug dependence or inability to give informed consent
3. Contraindications to use of mesalazine as detailed in summary of product characteristics (SmPC)
4. Inability to stop non-steroidal anti-inflammatory drugs (NSAIDs) or long term antibiotics
5. The use of specific concomitant medications
6. Presence of other gastrointestinal inflammatory conditions such as ulcerative colitis, Crohn's disease and Coeliac disease
Recruitment start date
01/08/2008
Recruitment end date
01/01/2011
Locations
Countries of recruitment
United Kingdom
Trial participating centre
Nottingham Digestive Disease Centre
School of Medicine
The University of Nottingham
E Floor, West Block, QMC
Nottingham
NG7 2UH
United Kingdom
Sponsor information
Organisation
University of Nottingham (UK)
Sponsor details
c/o Paul Cartledge
King's Meadow Campus
Lenton Lane
Nottingham
NG7 2NR
United Kingdom
Sponsor type
University/education
Website
Funders
Funder type
Charity
Funder name
Wellcome Trust (grant ref: 086609)
Alternative name(s)
Wellcome
Funding Body Type
private sector organisation
Funding Body Subtype
international
Location
United Kingdom
Results and Publications
Publication and dissemination plan
Planned publication in a peer-reviewed journal.
IPD sharing statement
The datasets generated and/or analysed during the current study during this study will be included in the subsequent results publication.
Intention to publish date
Participant level data
Other
Basic results (scientific)
See https://www.clinicaltrialsregister.eu/ctr-search/trial/2006-006198-26/results
Publication list
2012 abstract in: https://gut.bmj.com/content/61/Suppl_2/A51.3