T1396 Randomized Controlled Trial of the Selective Serotonin Reuptake Inhibitor (SSRI) Citalopram (CIT) vs. Placebo (PLC) in Non-Depressed Patients with Irritable Bowel Syndrome (IBS)

T1393

54.4hr(47.0,61.8); p=0.026] were accelerated, along with a normalisation in stool consistency [1.2 discrepancy from normal (0.9, 1.5) v 1.6 (1.3, 1.9); p=0.058]. Conclusion: FM accelerates transit and improves distension and associated symptoms in patients with IBS-C, suggesting that it may have value in alleviating symptoms. Refs: 1) Agrawal et al, DDW 2006; A93; 2) Marteau et al, Aliment Pharm Ther 2002; 16:587; 3) Houghton et al, Gastroenterol 2006;131:1003

AGA Abstracts

Fluvoxamine Versus Amitryptiline in Females with IBS and Depression Dan L. Dumitrascu, Liliana David Background and aim IBS still needs a perfect therapy. Depression is a common disorder in IBS. Several trials showed the benefit of antidepressants in IBS. We looked for the effect of a SSRI, fluvoxamine vs a TCA, amitryptiline in depressed females with IBS. Methods Subjects: 80 female pts with IBS filling the Rome II criteria and with depression scores on the Beck Depression Inventory were selected in a tertiary center. Protocol: The pts were randomized in 2 groups: group I received fluvoxamine 50 mg at bedtime 4 weeks; group II received amitryptiline 25 mg at bedtime 4 weeks. Both groups were comparable in respect to age and depression score. Pts were avoided other medication for digestive symptoms during the trial. The effect of the drugs was assessed for 4 main symptoms with a symptom score looking for intensity and frequency of symptoms according to a validated scale from 0 to 4, thus allowing values from 0 to 16. Results From the 80 pts, 72 finished the study (36 in each leg), the other quit due to insatisfaction with the study drugs. Symptom score for abdominal pain was decreased from 11.7+3.1 to 5.3+3.3 (p=0.020) in group I and from 12.5+4.0 to 6.2+4.5 (p=0.038) in group II. Bloating score was improved from 8.9+3.2 to 5.4+2.1 (p=0.040) in group I and from 7.7+2.7 to 4.6+3.2 in group II (p=0.035). Diarrhea and constipation scores were not significantly changed. BDI scores were similarly decreased by both drugs, from 21.3+6.2 to 14.7+6.0 in group I (p=0.015) and from 24.2+5.9 to 16.0+7.2 in group II (p=0.008). Less side-effects were recorded in group I vs group II (dry mouth: 4 vs 10 cases, dizzines: 3 vs 7cases, somnolence 8 vs 13 cases). Conclusions Fluvoxamine and amitryptiline similarly improve digestive symptoms: pain and bloating as well as depression scores in females with IBS and depression. However fluvoxamine produces less secondary effects but there number is still high.

Data expressed as mean (range) T1396 Randomized Controlled Trial of the Selective Serotonin Reuptake Inhibitor (SSRI) Citalopram (CIT) vs. Placebo (PLC) in Non-Depressed Patients with Irritable Bowel Syndrome (IBS) Uri Ladabaum, Annie Sharabidze, Theodore R. Levin, Wei K. Zhao, Elaine H. Chung, Peter Bacchetti, Chengshi Jin, Barbara A. Grimes, Craig J. Pepin

T1394 Mesalazine Treatment for Intestinal Immune Activation in Patient with Irritable Bowel Syndrome: A Randomized Controlled Pilot Trial Giovanni Barbara, Cesare Cremon, Luciana Gargano, Roberto De Giorgio, Rosanna Cogliandro, Vincenzo Stanghellini, Roberto Corinaldesi

BACKGROUND: SSRIs are often used to treat IBS but data on efficacy are scant. The potential benefit of SSRIs in IBS may be due to treatment of coexisting depression. IBS patients display visceral hypersensitivity, but its relationship to symptoms is controversial. AIMS: To assess the impact of CIT vs. PLC on clinical symptoms, quality of life and visceral sensitivity in non-depressed IBS patients (Rome II). METHODS: Patients were randomized to CIT (20 mg/d x4 wks, escalated to 40 mg/d x4 wks if tolerated) vs. PLC x8 wks. Adequate relief, symptoms and satisfaction were scored weekly. Response was defined as ≥3 wks of adequate relief in the last 6 wks, with missing data counted as no adequate relief for intention-totreat (ITT) analyses. Quality of life (IBS-QOL) and visceral sensitivity (rectal barostat) were assessed at wks 0 and 8. RESULTS: 27 patients were assigned to each group, with similar group characteristics: overall mean age 52 ±14 yrs, 82% female, 83% white, and IBS subtype 39% constipation, 43% diarrhea, 18% alternator. Drop-outs were 7 (26%) for CIT and 2 (7%) for PLC (P=0.14). ITT response rates were 44% for CIT and 56% for PLC (P=0.59), a risk difference of -11% (CI -38% to +15%). In a mixed effects logistic regression, the odds ratio for adequate relief with CIT vs. PLC was estimated as 0.80 per wk of use (CI 0.611.04) assuming a linear effect after wk 2. Weekly adequate relief, pain, urgency, bowel symptoms and satisfaction scores did not strongly favor CIT. IBS-QOL overall scores improved in both groups (change of 6.3 ±13.7 for CIT vs. 7.6 ±12.4 for PLC on a scale to 100, P=0.47). There were trends for differences between groups in baseline rectal pressure thresholds for pain (32 ±13 mm Hg vs. 24 ±12 mm Hg, P=0.07) and urgency (11 ±5 mm Hg vs. 8 ±6 mm Hg, P=0.12) for CIT vs. PLC, but the change in thresholds for wk 8 vs. 0 were similar (pain threshold change of -1.2 ±6.9 mm Hg for CIT vs. -1.2 ±6.1 mm Hg for PLC, P=0.9; urgency threshold change of 3.6 ±8.5 mm Hg for CIT vs. 3.5 ±9.3 mm Hg for PLC, P=0.8). Changes in overall IBS symptoms, pain or urgency scores from wk 1 to 8 were not significantly correlated with changes in barostat symptom thresholds. CONCLUSION: The SSRI citalopram did not appear to be superior to placebo in treating symptoms, improving quality of life, or modifying visceral sensitivity in non-depressed IBS patients. The lack of correlation between clinical symptoms and visceral sensory changes raises questions about the precise role of visceral hypersensitivity in the pathophysiology of IBS. Our results provide fairly strong evidence against a substantial benefit of citalopram in nondepressed IBS patients.

Background & Aims: Immune activation may play a role in the pathogenesis of irritable bowel syndrome (IBS). However, the role of anti-inflammatory drugs on intestinal immune activation and the potential clinical relevance of these drugs in IBS remains unsettled. Therefore, we carried out a pilot double blind placebo controlled trial to test the effect of mesalazine on mucosal immune activation (primary end-point) and symptom scores (secondary end-point) in IBS. Methods: Twenty IBS patients (13 females and 7 males, mean age 41.5±10.64) were recruited in the study after a positive diagnosis based on Rome II criteria. After a two week run-in period, the patients were randomized at the basal visit (T0) to receive either mesalazine (800 mg tablets t.i.d.) or placebo (tablets t.i.d.) for eight weeks (T8). Symptoms (abdominal pain and global relief) were assessed using validated questionnaires throughout the study. Colonic immunocytes were assessed using quantitative immunohistochemistry on colonic mucosal biopsies at T0 and T8. Results: In both intention to treat (ITT) and per protocol (PP) analyses, the total number of immnune cells and mast cells, but not T cells (CD3+, CD4+, CD8+), B cells (CD79+) or macrophages (CD68+), decreased significantly in patients treated with mesalazine, but not in those receiving placebo. Concerning mast cells, the treatment difference at T8 was - 36.17% vs. placebo in the ITT analysis (P<0.0001) and - 35.41% in the PP analysis (P=0.0009). The pain severity score decreased over time in patients treated with mesalazine with a significant difference vs placebo at T4 (-24%; P=0.0026) and T8 (- 40.4%; P=0.004). Global relief improved over time and was significantly greater in mesalazine treated patients in comparison with placebo at T4 (P=0.0007) and T8 (P= 0.0009) time points, with 26.89% difference over placebo at T8. Conclusions: Mesalazine, but not placebo markedly reduce the total number of mucosal immune cells and mast cells in the colonic mucosa of IBS patients. These changes were accompanied by a greater symptom improvement (abdominal pain and global relief) compared with placebo. This pilot study provides the rationale to test the efficacy of mesalazine on IBS symptoms in larger controlled trials. T1395

T1397

Fermented Milk Containing the Probiotic Bifidobacterium Animalis, DN-173 010 (FM) Improves Abdominal Distension, Bloating and Transit in Irritable Bowel Syndrome with Constipation (IBS-C) Anurag Agrawal, Lesley A. Houghton, Julie Morris, Denis Guyonnet, Nathalie Goupil Feuillerat, Armelle Schlumberger, Stefan Jakob, Peter J. Whorwell

A Novel, Oral 5HT3 Partial Agonist, DDP733, Improves Overall Response in Patients with Irritable Bowel Syndrome and Constipation (IBS-c): A Randomized, Double Blind, Placebo-Controlled, Parallel-Group, Dose-Ranging Study William G. Paterson, David Ford, Subhas C. Ganguli, Richard P. Reynolds, Lew Pliamm, Michael O'Mahony, Pierre Pare, Suhail Nurbhai, Brian Feagan, Steven B. Landau

Introduction: In IBS-C delayed transit is associated with an increase in abdominal girth (distension) (1) suggesting that accelerating transit might reduce distension and bloating. FM has been shown to improve transit in healthy adults (2) and this study aimed to evaluate the effect of FM on distension, bloating, and associated symptoms, as well as small (SBT) and large (LBT) bowel transit in IBS-C. Methods: A single-centre, double-blind, placebocontrolled, parallel design study in which 34 IBS-C (Rome III, aged 20-69 yr) female patients with bloating were randomised to ingest daily either 2 x 125g of FM (a yogurt symbiosis and the specific probiotic Bifidobacterium animalis DN-173 001, 1.2x1010 colony forming units (cfu) per 125g) or placebo for 28 days. At the beginning and end of intervention, 24hr abdominal girth was measured using Abdominal Inductance Plethysmography (3), along with SBT and LBT. In addition, the symptoms of bloating, flatulence, pain and overall IBS score (scale 1-6), along with stool consistency were recorded daily for 11 days before and during 28 days of intervention. Data were analysed using ANOVA techniques, correcting for baseline value measures, age and BMI. Results: Pre-intervention data are summarised in table. Following intervention, patients on FM exhibited less distension [FM, 1.1 cm(-0.1, 2.4), mean (95% CI) v control, 2.6 cm(1.4,3.9); p=0.096], bloating [3.4(3.0,3.8) v 4.0(3.6,4.4); p= 0.059], flatulence [3.2(2.8,3.6) v 3.6(3.3,4.0); p=0.092], pain [3.0 (2.7,3.4) v 3.5(3.2,3.9); p=0.044] and overall IBS severity [3.3(2.9,3.6) v 3.8(3.5,4.2);p=0.032] than those on placebo. SBT [5.4 hr(4.6,6.2) v 6.6 hr(5.8,7.4); p=0.049] and LBT [42.2 hr(34.8, 49.6) v

AGA Abstracts

Background: IBS-c is a common disorder that results in important disability and economic loss. New treatments are required. DDP-733 is an oral 5-HT3 partial agonist without significant intestinal absorption that increased intestinal motility in a previous study in patients with slow intestinal transit. We conducted a 4-week multicenter, outpatient, dose-ranging study of DDP733 in patients with IBS-c as defined by the Rome II Criteria. Methods: 91 subjects (81 female) were randomized in a double-blind fashion to one of five treatment groups: placebo, 0.2, 0.5, 0.8 or 1.4 mg DDP733 administered three times per day for 28 days. Patients used a diary to record their overall global assessment of relief of IBS, as well as data related to specific IBS symptoms, study medication, rescue medication use, and adverse events. Gastrointestinal transit was assessed at baseline and end of treatment using radio-opaque markers. Safety was assessed by adverse event (AE) incidence rates and clinical laboratories. Results: For the protocol defined primary clinical analysis of Overall Subject Global Assessment (SGA) at day 28, 53.8% of subjects in the 1.4 mg dose group were responders compared to 15.4% of subjects in the placebo group (p = 0.039). No other groups were statistically different from placebo. The difference over placebo for the highest

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