The impact of assessing and treating bile acid malabsorption on function and quality of life in patients with major Low Anterior Resection Syndrome (LARS).

This is a prospective randomised controlled study comparing colesevelam therapy with placebo in a two-period cross-over design, where patients will act as their own controls. Radiological testing for Bile acid malabsorption (BAM) will be performed in a subset of participants prior to the intervention being administered. We aim to test at least half of the participants, but this will be determined by funding and access to radiology. We anticipate that 3-15 patients will undergo this test. Selection will be based on the test being available when the individual is recruited. The SeHCAT test involves administering 75Se 23-selena-25-homocholic acid and glycocholic acid as an oral capsule to a fasting patient. The initial count rate of 75Se will be measured three hours after the intake of the isotope. On day 7 following administration, there will be further imaging, and the net count rate of 75Se will be expressed as a percentage of the net count rate at day 0. The % retention of 75Se will be recorded. While a positive test is one that shows a retention <15%, the actual levels of 75Se will also be compared to changes in the LARS score. A 2-sequence, 2-period design will be used with a six-week washout between interventions to account for first-order carryover effects. Participants will be randomised to one of the following sequences: AB|BA, where A=colesevelam therapy and B=placebo. The intervention will be presented as 312mg capsules. The participant will start by taking two capsules (approximately 625mg) three times a day for three days, and if there are no side effects will then increase to four capsules (1.25g) three times a day. Side effects will be monitored by use of a daily patient diary and telephone interviews on days one and three. Patients will also be encouraged to contact the researcher if they experience any potential side effects. If after 3 days there are side effects, participants will then be dosed down to two capsules four times a day for 3 days, and then reduce down to two capsules three times a day for the remainder of the 35 days. This will be monitored through the use of the diary and telephone contact (Days 5,7,14, 21, 28, and 35). Participants will be advised to take the capsules with a full cup of water or juice, and to take the capsules at least two hours before or after taking any other medications. The capsules (colesevelam in the intervention arm) will be taken for 35 days, and adherence will be monitored through the use of the diary and drug tablet return if not taken. Following this, there will be a washout period of six weeks, after which the participants will then proceed to another five week period with the alternative treatment. After the first five-week period, there will be a washout period of six weeks. Patients will then receive alternative treatment for the next five weeks. The LARS score and quality of life measures: the short form 12 Health Survey (SF-12), and faecal incontinence QoL (FiQL) with be assessed prior to and immediately following each treatment period. Participants will keep a stool diary during the treatment and washout periods. Both the participants and assessors will be blinded to treatment with colesevelam or placebo.