Diarrhoea-predominant irritable bowel syndrome (IBS-D) Digestive System Irritable bowel syndrome
Conditions
Interventions
Current Interventions as of 13/01/2011:
Mesalazine granules or matching placebo for 12 weeks, with the week 1 of treatment at 2g, once a day, then a step increase to 2g, twice a day for the remainder
Sponsors
University of Nottingham (UK)
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Current inclusion criteria as of 13/01/2011: 1) Male or Female patients aged 18-75 years able to give informed consent. 2) Patients should all have had a colonoscopy within the last 12 months to exclude microscopic or any inflammatory colitis. (If not, but they have had a negative colonoscopy within 5 years and symptoms are unchanged, then a sigmoidoscopy and mucosal biopsy of the left colon would be sufficient to exclude microscopic or any inflammatory colitis). 3) IBS-D Patients meeting Rome III criteria prior to screening phase. 4) Patients with =25% soft (score >4) and <25% hard (score 1 or 2) stools during the screening phase, as scored by the daily symptom and stool diary*. 5) Patients with an average stool frequency of 3 or more per day during the screening phase*. 6) Satisfactory completion of the daily stool and symptom diary during the screening phase at the discretion of the investigator. 7) Women of child bearing potential willing and able to use at least one highly effective contraceptive method throughout the study. In the context of this study, an effective method is defined as those which result in low failure rate (i.e. less than 1% per year) when used consistently and correctly such as: implants, injectables, combined oral contraceptives, sexual abstinence or vasectomised partner. *If inclusion criterion 4 and/or 5 is/are not met but the results are considered atypical (as observed from medical history and patient recall) then the patient can be re-screen on 1 occasion only. Previous inclusion criteria: 1. IBS-D patients meeting Rome III criteria 2. Male or female patients aged 18 - 75 years 3. Able to give informed consent
Exclusion criteria
Exclusion criteria: Current exclusion criteria as of 13/01/2011: 1) Women who are pregnant or breast feeding 2) Prior abdominal surgery which may cause bowel symptoms similar to IBS (note appendectomy and cholecystectomy will not be an exclusion) 3) Patients unable to stop anti-muscarinics, anti-spasmodics, high dose tricyclic antidepressants (i.e. above 50 mg/day), opiates / anti-diarrhoeal drugs*, NSAIDs (occasional over the counter use and topical formulations are allowed), long-term antibiotics, other anti-inflammatory drugs or 5-ASA containing drugs. 4) Patients on selective serotonin re-uptake inhibitors and low dose tricyclic antidepressants (i.e. up to 50 mg/day) for at least 3 months previous unwilling to remain on a stable dose for the duration of the trial. 5) Patients with other gastro-intestinal diseases including colitis and Crohn?s disease. 6) Patients with the following conditions: Renal impairment, severe hepatic impairment or salicylate hypersensitivity. 7) Patients currently participating in another trial or have been in a trial within the previous 3 months 8) Patients who in the opinion of the investigator are considered unsuitable due to inability to comply with instructions 9) Patients with serious concomitant diseases e.g. cardiovascular, respiratory, neurological etc. *Loperamide is allowed as rescue medication through-out the trial, however if >2 doses / week are taken during the screening phase then they are not eligible, though they can be re-screened on 1 occasion only. Previous exclusion criteria: 1. Women who are pregnancy or breast feeding or women of child bearing potential who are not willing to use medically acceptable forms of contraception during the study, (e.g. implants, injectables, combined oral contraceptives, sexual abstinence or vasectomised partners) 2. Prior abdominal surgery which may cause bowel symptoms similar to IBS (note appendectomy and cholecystectomy will not be an exclusion) 3. Patients unable to stop anti-diarrhoeal drugs, non-steriodal anti-inflammatory drugs (NSAIDs) (occasional over the counter use is allowed), other anti-inflammatory drugs (azathioprine or related drugs) or already taking 5-aminosalicylic acid (5-ASA) containing drugs. 4. Patients with other gastro-intestinal diseases including colitis and Crohn's disease 5. Patients with the following conditions: renal impairment, severe hepatic impairment or salicylate hypersensitivity 6. Patients currently participating in another trial or have been in a trial within the previous 3 months 7. Patients who in the opinion of the investigator are considered unsuitable due to inability to comply with instructions
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Average stool frequency during weeks 11 - 12 of the treatment period. | — |
Secondary
| Measure | Time frame |
|---|---|
| Current secondary outcome measures as of 13/01/2011: Clinical secondary endpoints: 1. Average daily severity of abdominal pain on a 0 - 10 scale 2. Days with urgency during weeks 11 - 12 post-randomisation 3. Mean stool consistency using Bristol Stool Form Score 4. Global satisfaction with control of IBS symptoms as assessed from the answer to the question "Have you had satisfactory relief of your IBS symptoms? Yes/No" Mechanistic secondary endpoints: 1) Mast cell tryptase release during 6 hour biopsy incubation 2) IL-1ß, TNF-a, histamine and serotonin secretion during same incubation 3) Small bowel tone assessed by volume of fasting small bowel water 4) Faecal Tryptases 5) Difference in primary outcome measure between those with different TNFSF15 polymorphism will be assessed using ANOVA Ancillary secondary endpoints: 1) EQ-5D 2) CDC HRQOL4 3) HADS 4) PHQ-15 Previous secondary outcome measures: Clinical secondary endpoints: 1. Average daily severity of abdominal pain on a 0 - 10 scale 2. Days with urgency during weeks 11 - 12 post-randomisation 3. Mean stool consistency using Bristol Stool Form Score 4. Global satisfaction with control of IBS symptoms as assessed from the answer to the question "Have you had satisfactory relief of your IBS symptoms? Yes/No" Mechanistic secondary endpoints: 5. Mast cell tryptase release during 6-hour biopsy incubation 6. Interleukin-1 (IL-1), tumour necrosis factor-alpha (TNF-a), histamine and serotonin secretion during same incubation 7. Small bowel tone assessed by volume of fasting small bowel water Ancillary secondary endpoints, measured at time 0 and 12 weeks (before and after treatment): 8. EQ-5D (standardised instrument for use as a measure of health outcome) 9. Centers for Disease Control and Prevention Health-Related Quality-of-Life, 4-item set of Healthy Days core questions (CDC HRQOL4) | — |
Countries
United Kingdom
Outcome results
None listed