A Dose-Ranging, Double-Blind, Placebo-Controlled Study of Lubiprostone in Subjects with Irritable Bowel Syndrome and Constipation (c-IBS) [Abstract 131]
Irritable bowel syndrome (IBS) affects millions of people in America and is difficult to diagnose and treat effectively due to its variability of symptoms. Current therapies work on select patient populations, but are limited in efficacy and have significant side effects. In this study, researchers examine the use of a novel therapy as an effective and safe new option for IBS patients.
Lubiprostone, a novel type-2 chloride channel (ClC-2) activator, has shown positive results and good tolerability in previous trials of patients with chronic constipation. The therapy increases fluid secretion, which works to improve function in the gastrointestinal system. This study tested different doses of lubiprostone over 12 weeks in subjects with constipation-specific IBS (c-IBS), as defined by the Rome II Criteria, which outlines symptoms and applies parameters such as frequency and duration to more accurately diagnose IBS.
Approximately 50 patients were randomized to each of four treatment groups: placebo or 16, 32 or 48 µg lubiprostone daily. Patients were asked to keep a log of their progress, including dose, abdominal symptoms like bloating and discomfort or pain, bowel movements (BMs) including frequency, straining, and consistency ratings, as well as the use of rescue medication.
Study results revealed significant differences between the active groups and placebo. Specifically, improvements in abdominal discomfort/pain and BM frequency rates in the lubiprostone-treated groups were more than twice those of the placebo group. At month one, decreases from baseline in abdominal discomfort (based on a 5-point scale) were 0.19, 0.45, 0.40, and 0.46 points in the placebo and three dosage groups, respectively. By month three, decreases from baseline were 0.34, 0.56, 0.59, and 0.53 points, respectively. Significant dose-dependent trends were observed for most of the symptoms. AE incidence and drop-out rates likewise increased with increasing dose.
"Overall, improvements in patient symptoms were observed for all doses, although highest in the group receiving the highest lubiprostone dose," said John Johanson, M.D., Rockford Gastroenterology Associates and lead study author. "The results demonstrate that lubiprostone is effective and well-tolerated as an option for patients with c-IBS, and further studies will confirm the optimal dose to maximize effect, but minimize potential safety issues."
Effect of Teduglutide on Patients with Moderate-Severe Crohn's Disease after 8 Weeks of Therapy: A Prospective Double-Blind, Placebo Controlled Trial [Abstract 686c]
Crohn's disease causes inflammation in the gastrointestinal tract. Average clinical remission rates are generally less than 40 percent in most clinical trials. In this study, a new therapy called teduglutide targets mucosal healing in addition to mucosal inflammation. The theory behind the use of this medication is to promote growth and repair of the injured tissues. In previous animal studies of inflammatory bowel disease, teduglutide has reduced inflamation and healed injured intestinal tissue.
In the exploratory study, 100 participants with active Crohn's disease were randomized and treated with one of three doses of teduglutide or placebo for eight weeks to determine rates of remission (CDAI less than 150) or clinical response (greater than 100 point decrease in CDAI from baseline).
While the trial did not evaluated dose-dependent comparisons, teduglutide was considered well-tolerated and effective in achieving remission and response in patients with moderate or severe Crohn's disease. Half of the teduglutide patients (53 percent) responded after two weeks of therapy and more than one-third (37 percent) experienced remission at the same time. After the full eight week regimen, researchers noted a clinical response in 61 percent of the treated group and remission in more than half (56 percent).
"These data note that use of teduglutide was safe and effective to induce remission of moderate to severe Crohn's disease as early as two weeks into therapy," said Alan Buchman, M.D., MSPH, Feinberg School of Medicine, Northwestern University, and lead study author. "We are encouraged that with additional trials to confirm the maximal effective dose, this therapy will offer a novel alternative to treat patients with Crohn's disease who have not responded to other therapies."
Teduglutide is an analog of the naturally occurring human peptide Glucagon Like Peptide-2 (GLP-2). GLP-2 is a peptide growth factor secreted in the distal intestine and is involved in regeneration, maintenance and repair of the intestine. Adverse events with teduglutide were generally self-limited, mild in nature and included abdominal pain and injection site reactions. There were no drug-related serious adverse events.
Digestive Disease Week® (DDW) is the largest international gathering of physicians, researchers and academics in the fields of gastroenterology, hepatology, endoscopy and gastrointestinal surgery. Jointly sponsored by the American Association for the Study of Liver Diseases (AASLD), the American Gastroenterological Association (AGA), the American Society for Gastrointestinal Endoscopy (ASGE) and the Society for Surgery of the Alimentary Tract (SSAT), DDW takes place May 20-25, 2006 in Los Angeles, California. The meeting showcases more than 5,000 abstracts and hundreds of lectures on the latest advances in GI research, medicine and technology.
Last reviewed: By John M. Grohol, Psy.D. on 21 Feb 2009
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