The use of Nalcol™ in functional constipation

INTERVENTION: This is a single‐centre double‐blind placebo‐controlled study of the efficacy and safety of Nalcol™ given to patients with refractory constipation attending a specialist clinic. The study is principally a phase II trial of short‐term (4 weeks) effect. It is suspected that Nalcol™ will have a moderate effect, and is used here as an adjuvant to regular laxatives. The patients will all fulfil criteria for functional constipation (as above) and will have attended a specialist gastroenterology or colorectal clinic at the Norfolk and Norwich University Hospital. They will have undergone investigation for their constipation with barium enemas and also transit studies and their basic management, including dietary and lifestyle advice and modification of laxatives, will have been instigated. The key treatment phase (Period 2) will last 4 weeks and data over 4 weeks of treatment will be available. Two weeks of pre‐treatment data will be collected during the screening period before randomisation (Period 1). This will allow an assessment of patient suitability and health to ensure that the inclusion criteria are met and permit examination with a rigid sigmoidoscope to obtain a rectal biopsy and stool sample. This initial period will ensure short‐term symptom stability and confirm patient compliance with diary completion. It will allow secondary analyses comparing pre‐treatment and treated symptom scores and quality of life (QoL) data. A final phase of 4 weeks (Period 3) will allow all patients in the trial to evaluate the treatment and provide further observation over a more prolonged duration. Nalcol™ is given to relieve symptoms, which may be variable from day‐to‐day. The tolerability of Nalcol™ tablets is expected to be comparable to that of commonly dispensed stimulant laxatives; with no significant systemic side effects. It is known that 10 mg, twice a day is effective in increasing gut motility in normal subjects and a group of patients have taken 40 mg daily and occas CONDITION: Constipation ; Digestive System ; Other functional intestinal disorders PRIMARY OUTCOME: Comparison of the responders during Period 2 of the study (weeks 3 ‐ 6) in the treatment group and those in the placebo group. Response is defined as those participants who give an assessment of 'satisfactory improvement' on at least 50% of occasions over the 4‐week trial period (Period 2) to the global question on the diary card. INCLUSION CRITERIA: 1. Aged greater than 18 years 2. Male or female 3. Satisfy Rome III criteria for functional (slow transit) constipation 4. Symptoms not relieved by diet and laxatives SECONDARY OUTCOME: 1. Comparison of stool frequency and type, laxative use, Patient Assessment of Constipation Symptoms (PAC‐SYM), and Patient Assessment of Constipation Quality of Life Questionnaire (PAC‐QOL) between treatment and placebo groups during Period 2 of the study. PAC‐SYM will be used to provide an overall symptom score; but each component will also be analysed separately to identify changes to individual symptoms. Comparison will be made between the pre‐ and post‐trial transit study as an objective marker of a reduction in transit time.; 2. Graphical representation of the temporal changes in stool frequency and type and analysis to assess any drop‐off of effect after 8 weeks of use in those receiving Nalcol™ for 8 weeks or in the whole group; 3. A comparison of pre‐treatment versus treatment symptom levels in the whole (n = 120), i.e., Period 1 versus Period 3; 4. Comparison of stool bacterial counts between the treatment and placebo groups in the selected subset after each Period