P. P. TOSKES*, K. L. CONNERY* & T. W. RITCHEY
Calcium polycarbophil was compared with placebo in 23 patients with irritable bowel syndrome in a sixmonth, randomized double-blind crossover study. Patients received polycarbophil tablets at a dosage of 6 g/day (twelve 0.5-gtablets) or matching placebo tablets. At study end, among patients expressing a preference, 15 of 21 (71%) chose polycarbophil over placebo for relief of the symptoms of irritable bowel syndrome. Statistically significant differences favouring polycarbophil were found among the following patient subgroups: 15 (79%) of 19 with constipation; all six with alternating diarrhoea and constipation: 13 (87%) of 15 with bloating; and 11 (92%) of 12 with two or more symptoms. Polycarbophil was rated better than placebo in monthly global responses to therapy. Patient diary entries showed statistically significant improvement for ease of passage with polycarbophil. Polycarbophil was rated better than placebo for relief of nausea, pain, and bloating. The data suggest that calcium polycarbophil can benefit irritable bowel syndrome patients with constipation or alternating diarrhoea and constipation and may be particularly useful in patients with bloating as a major complaint.
Irritable bowel syndrome is a frequently occurring digestive disorder, affecting as much as 15% of the population of developed countries. It has been estimated that 70% of patients seeking medical help from a gastroenterologist have irritable bowel syndrome. Unfortunately, no treatment is clearly efficacious and therapy is typically directed at providing relief for the associated symptoms. Through various mechanisms, most standard therapies attempt to modify colonic motor activity in order to restore normal bowel function. High-fibre diets and buIking agents are commonly used to normaIize bowel function and are recommended in therapeutic programs for the management of irritable bowel syndrome. However, the results of clinical trials with wheat fibre, ispaghula husk, and psyllium preparations have been inconsistent.
In a double-blind, placebo-controlled trial, statistically significant improvement in irritable bowel syndrome symptoms was seen with ispaghula as a single-agent and when used in combination with lorazepam and hyoscine b~tylbromide. Prior and Whorwell' reported that ispaghula was rated significantly better than placebo by global assessment and resulted in statistically significant improvements in constipation and transit time. In a study to determine the optimum dose, ispaghula, at 20 and 30 g/day, caused significant improvement in symptoms of constipation, diarrhoea, and pain in irritable bowel syndrome patients. Manning et al. reported significant improvement in symptoms and an objective change in colonic motor activity in patients treated with a high-wheat-fibre regimen. In contrast, other investigations failed to demonstrate that bulking agents or high-fibre diets produced significant improvements in the symptoms of irritable bowel syndrome patients.
Calcium polycarbophil is among those bulking agents prescribed to relieve the symptoms of irritable bowel syndrome. However, at this time, there are no published studies that report the use of calcium polycarbophil in irritable bowel syndrome. This study reports a doubleblind, crossover comparison of calcium polycarbophil with placebo to assess the efficacy and acceptance of calcium polycarbophil and to clarify its role in the treatment of irritable bowel syndrome.
Twenty-eight patients with irritable bowel syndrome, 8 males and 20 females, ranging in age from 20 to 69 years of age, were enrolled sequentially in a randomized, placebo-controlled, two-way crossover study. Eligibility for entry was a diagnosis of irritable bowel syndrome defined as one or more of the following criteria present for at least 3 months and occurring at least twice weekly: constipation with associated bloating, distension, or abdominal pain: continuous or intermittent diarrhoea with abdominal pain; or alternating diarrhoea and constipation accompanied by abdominal pain. Eligible patients had no clinically significant deviations from normal ranges in pre-study clinical laboratory tests and no evidence of organic bowel disease as determined by a barium enema within the previous 24 months and a sigmoidoscopy within the previous 12 months. Females were required to have a negative pregnancy test before participation. Patients with diabetes, lactose intolerance, or a history of kidney stones, gastrointestinal malignancy, gastrointestinal surgery, or any significant condition that would interfere with the study were excluded. Patients were excludedfrom the analysis of results if they required any of the following medications during the course of the study: other laxatives, anticholinergics, antidepressants, tranquilizers, sucralfate, intermittent courses of antibiotics, H2-receptor antagonists, or supplemental calcium. All subjects signed written informed consent before participation in the study.
At the start of the study, patients were randomly assigned to receive either calcium polycarbophil tablets (Fibercon, Lederle Laboratories, Pearl River, USA) at a dosage of 6 g/day (twelve 0.5-gtablets) in four divided doses, or matching placebo tablets for a period of 12 weeks (Period 1). Calcium polycarbophil is a synthetic hydrophilic colloid effectivein treating both constipation and diarrhoea. As a bulking agent, calcium polycarbophil possesses the property of water holding, which results in the formation of a gel through colloidal swe1ling. The placebo was composed of dicalcium phosphate and the usual incipients found in the active tablet. The amount of calcium in the placebo was equal to the amount found in the active tablet. Tablets were to be taken with 225 mg water. Patients then crossed over to receive the alternate treatment for 12 weeks (Period 2). Compliance was monitored by pill counts-all patients included in the analyses took at least 75% of the recommended dosage. Patient assessments of stool frequency, consistency, and ease of passage were recorded daily. Stool consistency was evaluated on a scale of 1= liquid, 2 = soft, 3 = average, and 4 = hard. Ease of passage was evaluated as 1= no strain and 2 = strain. Subjective assessments of nausea, bloating, and abdominal pain were recorded daily and scored as 1 = none, 2 = mild, 3 = moderate, and 4 = severe. At the end of each month, patients evaluated the current treatment on a four-point rating scale of 1= excellent, 2 = good, 3 = fair, and 4 = poor. At the end of the study, patients were asked to express an overall preference, based on relief of irritable bowel syndrome symptoms, for either the first or second treatment.
Overall patient preference for calcium polycarbophil or placebo was analysed using the binomial distribution (two-sided hypothesis). Monthly global evaluations and daily diary entries for ease of passage, bloating, nausea, and pain were evaluated by an analysis of variance that incorporated sequence, period, patient, month, treatment, and all possible two-way interactions. Comparisons were made after eliminating nonsignificant twoway interactions.