S1316 Patient Willingness to use ROSE-010: A Subcutaneous (SC) GLP-1 Analogue for IBS Pain Episodes
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cases with suspected functional bowel disease except for our 41 yo cases. Initial Tx greatly favored osmotic laxatives regardless of the age. Failure of initial Tx resulted in great ambiguity of a dominant 2 o Tx strategy. We conclude that there is incomplete adherence to national guidelines that is influenced by physician gender and practice setting. ^χ 2 test:P<0.05 S1314 The Effect of Probiotic Mixture on the Symptoms and Fecal Microbiota in Diarrhea-Dominant Irritable Bowel Syndrome: Randomized, Double-Blind, Placebo-Controlled Trial Bong Ki Cha, Chang Hwan Choi, Eun Kyung Baek, Hyun Woong Lee, Jae Hyuk Do, Sae Kyung Chang Background & Aims: Some reports suggest that probiotics are helpful for treatment of Irritable bowel syndrome (IBS). The aim of this study was to evaluate the effects of probiotic mixture compared with placebo on the symptoms and the compositions of fecal microbiota in patients with diarrhea-dominant IBS (D-IBS). Methods: Forty-seven patients with D-IBS consented by ROME III were randomized in a parallel group, double-blind design to placebo or seven probiotics mixture 7x10 11 CFU (Streptococcus thermophous, Lactobacillus plantarum, Lactobacillus acidophilus, Lactobacillus rhamnosus, Bifidobacterium lactis, Bifid- obacterium longum, Bifidobacterium breve) daily for 8 weeks after 1-week run-in period. The primary outcome was the adequate relief (AR) for overall IBS symptoms; secondary outcomes included the individual IBS symptoms, and the IBS quality of life (IBS-QOL). The AR was weekly checked by questionnaire for 10 weeks (8 weeks of treatment phase, 2 weeks of post-treatment phase). The IBS symptom diary based on visual analogue scale (VAS for abdominal pain, abdominal discomfort, diarrhea, urgency, mucus in stool, bloating, passage of gas) and stool parameters (hardness and frequency) were recorded on a daily basis and assessed each week for 11 weeks. IBS-QOL assessment and stool sampling for evaluating the composition of fecal microbiota by denaturing gradient gel electrophoresis (DGGE) were performed at the beginning and at the end of the treatment phase. Results: For all weeks, the proportions of AR was higher in probiotics group than placebo (p<0.05). The proportion of the patients who reported “yes” to adequate relief on half of the weeks (5 weeks) in the treatment trial was significantly higher in probiotics group than placebo (50% vs. 13%, p= 0.01). However, the improvements of the individual symptom scores and stool parameters were not superior in probiotics group. In IBS-QOL, the changing rates of overall scores for probiotics group tended to be higher than those for placebo (21.3±21.6% vs. 9.0±21.5%, p=0.073). The improvements of all 8 domains of IBS-QOL were consistently superior in probiotics group. In the comparison for DGGE profiles of fecal bacteria, there was no difference in the similarities of their bacterial compositions between the two groups. The concordance rates of bacterial compositions from the two time-points were 66.2±13.4% in probiotics and 69.1±11.8% in placebo group (p=0.519). Conclusion: The probiotic mixture is effective in providing adequate relief of overall IBS symptoms, and has a tendency to improve of IBS-QOL in D-IBS. But, the effect of probiotics is not related with the composi- tional changes of fecal microbiota. S1315 Identification of Novel Metabolites in Serum of Patients With Irritable Bowel Syndrome Sharat Singh, Gary Meyer, Hua Gong Background: Serotonin plays an important role in mediating GI motility, secretion, and sensation. Serotonergic therapies acting on serotonin receptors can effectively ameliorate symptoms that irritable bowel syndrome (IBS) patients experience. Study of serotonin meta- bolites may lead to identification of biologically relevant biomarkers that can be used for accurate diagnosis of IBS. The aim of this study was to profile levels of serotonin and its metabolites in healthy volunteers and IBS patients with different bowel habits, diarrhea predominant (IBS-D), constipation predominant (IBS-C), and diarrhea/constipation mixed (IBS-M). Methods: We developed and optimized an HPLC method using a diphenyl column to separate analytes in IBS and healthy controls. Serum from 12 IBS-C, 24 IBS-D, 14 IBS- M patients were compared with 38 healthy subjects. Plasma, serum and urine samples from the same subjects were also compared for levels of serotonin and its metabolites. We further characterized novel metabolites by extracting and purifying analytes of interest by preparative HPLC. The structures of the metabolites are being analyzed by LC-MS and NMR. Results: Using the HPLC methods we developed, we were able to separate over 20 peaks in human samples. In addition to the known analytes such as tryptophan and serotonin and its metabolites, 5-HT-O-S and kynurenine, we also identified several novel metabolites with retention time at 7.5 min, 13.5 min, 52 min by fluorescent detector and at 20 min by UV detector. We are in the process of isolating a large quantity of each peak in order to identify S-227 AGA Abstracts the structures. The serum serotonin concentrations in all three IBS subtypes were lower than those of healthy controls after being normalized by internal standards, a median AUC of 94.5 for healthy subjects, 66.9, 48.3, and 46.3 for IBS-C, IBS-D, and IBS-M respectively. The area under curve for the peaks at 7.5 and 13.5 min were higher in all three IBS subgroups after being normalized by serotonin. IBS-D patients had higher levels of 20 min UV peaks compared to IBS-C, IBS-M, and healthy volunteers. Conclusions: These findings suggest both novel and known serum metabolites may serve as biomarkers for the diagnosis of IBS, while caution needs to be taken in data interpretation as levels of serum metabolites may be affected by confounding factors. S1316 Patient Willingness to use ROSE-010: A Subcutaneous (SC) GLP-1 Analogue for IBS Pain Episodes Brennan M. Spiegel, Roger E. Bolus, Jennifer Talley, Lin Chang Background: There are few effective therapies for IBS pain. Phase II data reveal that a SC GLP-1 analogue (ROSE-010) reduces pain episode severity by 50% vs placebo (Hellström APT 2008). However, it is unclear whether IBS patients would use a SC agent for pain, and, if so, what minimum pain level would justify use. We described the prevalence and features of patients willing to use ROSE-010. Methods: We surveyed Rome III IBS patients from the Patient Reported Observed Outcomes & Function Cohort - an online clinical practice IBS registry. Patients viewed a description of ROSE-010 that presented the indication, method of administration (with image of agent being injected into abdomen), side effects (19% nausea; 8% headache; 3% vomiting), time to onset (10-60 min), & potential symptom benefits based on published data. We asked: Based on the information provided, and ignoring price or insurance coverage, if this medication were available how often would you use it when you have your IBS pain episodes? Options were: never, rarely, sometimes, most of the time & always. We dichotomized into willing (sometimes or greater) vs unwilling (never or rarely) to use ROSE-010. We performed t-tests comparing groups across severity metrics, including IBSSS, severity numeric rating scale (NRS), pain NRS, pain episode frequency, work produc- tivity (WPAI), & HAD. Those willing to use rated the minimal pain (0-10 NRS) that would trigger use. Results: Of 146 patients (age=42; 83% F; 16% IBS-C; 19% IBS-D; 65% IBS- M), the % never, rarely, sometimes, most of the time, and always willing to use were 19%, 24%, 29%, 10%, & 17%. The table shows data for willing vs unwilling groups. Other than HAD, all differences had p<0.05. Among those willing to use, the mean pain trigger was 7.8+2. Conclusions: Over half of IBS patients in a clinical practice cohort are willing to use ROSE-010 for pain episodes. But pain must be severe (nearly 8/10) to justify use. Those willing to use have higher symptom severity, more severe and frequent pain episodes, and lower productivity, but no difference in anxiety or depression. This suggests that ROSE- 010 may fulfill an unmet need for many IBS patients with impactful symptoms regardless of psychological traits. Willing vs Unwilling to use ROSE-010 S1317 Investigation and Management of Irritable Bowel Syndrome in Private Practice: An Audit Nicholas A. Kennedy, Marc F. LeMire, Alexander D. Rodgers, Peter A. Bampton Introduction: Irritable bowel syndrome (IBS) is responsible for up to 50% of consultations with gastroenterologists. This audit examines the manner in which it is investigated and managed in a large private practice. Methods: The electronic medical record system of the private practice was searched to to identify patients with a primary diagnosis of IBS. 557 patients were found of which 150 were randomly chosen and assessed and 117 found to meet inclusion criteria. The records of these patients were then reviewed retrospectively by an independent examiner (NK) and data regarding symptoms, investigation and management were recorded in a database. Data was then extracted from this database and analysed using a spreadsheet. Results: The mean age of the 117 patients included in the detailed analysis was 48.5 years, and 70.1% were female. Diarrhoea predominant IBS was the most represented subtype of IBS (39.3%) of the total, with most of the remainder approximately equally divided between constipation predominant, mixed and undetermined. Overall, 35.0% of patients met the Rome III criteria at the first visit, though this figure may reflect the retrospective nature of the data. Subsequent alternative diagnoses were made in 3 patients - lymphoma, ulcerative proctitis and infective colitis. None of these met Rome criteria and all had alarm features. The specialist requested one or more pathology tests for 54.7% of patients. 86.3% had one or more endoscopic procedures performed, most commonly colonoscopy. In 92.3% of patients, the decision for or against colonoscopy was consistent with the Gastroenterology Society of Australia guidelines. Only 4.5% of those having colonos- copy were recorded as having had a previous colonoscopy within the previous 5 years. The most common abnormalities on colonoscopy were polyps, diverticulosis and haemorrhoids. Management approaches included dietary advice (43.9%), lifestyle advice (30.7%), antispas- modics (19.3%), fibre supplements (16.7%), neuromodulators (11.4%) and probiotics (7.0%). 13.2% were referred to a dietician, but only 2.5% to a psychologist. Conclusions: This audit provides an insight into real-life practice in the investigation and management of IBS. It reveals a high rate for colonoscopy, suggesting that non-invasive modalities for AGA Abstracts
Transcript of S1316 Patient Willingness to use ROSE-010: A Subcutaneous (SC) GLP-1 Analogue for IBS Pain Episodes
cases with suspected functional bowel disease except for our 41 yo cases. Initial Tx greatlyfavored osmotic laxatives regardless of the age. Failure of initial Tx resulted in great ambiguityof a dominant 2o Tx strategy. We conclude that there is incomplete adherence to nationalguidelines that is influenced by physician gender and practice setting.
^χ2test:P<0.05
S1314
The Effect of Probiotic Mixture on the Symptoms and Fecal Microbiota inDiarrhea-Dominant Irritable Bowel Syndrome: Randomized, Double-Blind,Placebo-Controlled TrialBong Ki Cha, Chang Hwan Choi, Eun Kyung Baek, Hyun Woong Lee, Jae Hyuk Do, SaeKyung Chang
Background & Aims: Some reports suggest that probiotics are helpful for treatment ofIrritable bowel syndrome (IBS). The aim of this study was to evaluate the effects of probioticmixture compared with placebo on the symptoms and the compositions of fecal microbiotain patients with diarrhea-dominant IBS (D-IBS). Methods: Forty-seven patients with D-IBSconsented by ROME III were randomized in a parallel group, double-blind design to placeboor seven probiotics mixture 7x1011 CFU (Streptococcus thermophous, Lactobacillusplantarum, Lactobacillus acidophilus, Lactobacillus rhamnosus, Bifidobacterium lactis, Bifid-obacterium longum, Bifidobacterium breve) daily for 8 weeks after 1-week run-in period.The primary outcome was the adequate relief (AR) for overall IBS symptoms; secondaryoutcomes included the individual IBS symptoms, and the IBS quality of life (IBS-QOL). TheAR was weekly checked by questionnaire for 10 weeks (8 weeks of treatment phase, 2 weeksof post-treatment phase). The IBS symptom diary based on visual analogue scale (VAS forabdominal pain, abdominal discomfort, diarrhea, urgency, mucus in stool, bloating, passageof gas) and stool parameters (hardness and frequency) were recorded on a daily basis andassessed each week for 11 weeks. IBS-QOL assessment and stool sampling for evaluatingthe composition of fecal microbiota by denaturing gradient gel electrophoresis (DGGE) wereperformed at the beginning and at the end of the treatment phase. Results: For all weeks,the proportions of AR was higher in probiotics group than placebo (p<0.05). The proportionof the patients who reported “yes” to adequate relief on half of the weeks (5 weeks) in thetreatment trial was significantly higher in probiotics group than placebo (50% vs. 13%, p=0.01). However, the improvements of the individual symptom scores and stool parameterswere not superior in probiotics group. In IBS-QOL, the changing rates of overall scores forprobiotics group tended to be higher than those for placebo (21.3±21.6% vs. 9.0±21.5%,p=0.073). The improvements of all 8 domains of IBS-QOL were consistently superior inprobiotics group. In the comparison for DGGE profiles of fecal bacteria, there was nodifference in the similarities of their bacterial compositions between the two groups. Theconcordance rates of bacterial compositions from the two time-points were 66.2±13.4% inprobiotics and 69.1±11.8% in placebo group (p=0.519). Conclusion: The probiotic mixtureis effective in providing adequate relief of overall IBS symptoms, and has a tendency toimprove of IBS-QOL in D-IBS. But, the effect of probiotics is not related with the composi-tional changes of fecal microbiota.
S1315
Identification of Novel Metabolites in Serum of Patients With Irritable BowelSyndromeSharat Singh, Gary Meyer, Hua Gong
Background: Serotonin plays an important role in mediating GI motility, secretion, andsensation. Serotonergic therapies acting on serotonin receptors can effectively amelioratesymptoms that irritable bowel syndrome (IBS) patients experience. Study of serotonin meta-bolites may lead to identification of biologically relevant biomarkers that can be used foraccurate diagnosis of IBS. The aim of this study was to profile levels of serotonin and itsmetabolites in healthy volunteers and IBS patients with different bowel habits, diarrheapredominant (IBS-D), constipation predominant (IBS-C), and diarrhea/constipation mixed(IBS-M). Methods: We developed and optimized an HPLC method using a diphenyl columnto separate analytes in IBS and healthy controls. Serum from 12 IBS-C, 24 IBS-D, 14 IBS-M patients were compared with 38 healthy subjects. Plasma, serum and urine samples fromthe same subjects were also compared for levels of serotonin and its metabolites. We furthercharacterized novel metabolites by extracting and purifying analytes of interest by preparativeHPLC. The structures of the metabolites are being analyzed by LC-MS and NMR. Results:Using the HPLC methods we developed, we were able to separate over 20 peaks in humansamples. In addition to the known analytes such as tryptophan and serotonin and itsmetabolites, 5-HT-O-S and kynurenine, we also identified several novel metabolites withretention time at 7.5 min, 13.5 min, 52 min by fluorescent detector and at 20 min by UVdetector. We are in the process of isolating a large quantity of each peak in order to identify
S-227 AGA Abstracts
the structures. The serum serotonin concentrations in all three IBS subtypes were lowerthan those of healthy controls after being normalized by internal standards, a median AUCof 94.5 for healthy subjects, 66.9, 48.3, and 46.3 for IBS-C, IBS-D, and IBS-M respectively.The area under curve for the peaks at 7.5 and 13.5 min were higher in all three IBS subgroupsafter being normalized by serotonin. IBS-D patients had higher levels of 20 min UV peakscompared to IBS-C, IBS-M, and healthy volunteers. Conclusions: These findings suggestboth novel and known serum metabolites may serve as biomarkers for the diagnosis of IBS,while caution needs to be taken in data interpretation as levels of serum metabolites maybe affected by confounding factors.
S1316
Patient Willingness to use ROSE-010: A Subcutaneous (SC) GLP-1 Analoguefor IBS Pain EpisodesBrennan M. Spiegel, Roger E. Bolus, Jennifer Talley, Lin Chang
Background: There are few effective therapies for IBS pain. Phase II data reveal that a SCGLP-1 analogue (ROSE-010) reduces pain episode severity by 50% vs placebo (HellströmAPT 2008). However, it is unclear whether IBS patients would use a SC agent for pain, and,if so, what minimum pain level would justify use. We described the prevalence and featuresof patients willing to use ROSE-010. Methods: We surveyed Rome III IBS patients fromthe Patient Reported Observed Outcomes & Function Cohort - an online clinical practiceIBS registry. Patients viewed a description of ROSE-010 that presented the indication, methodof administration (with image of agent being injected into abdomen), side effects (19%nausea; 8% headache; 3% vomiting), time to onset (10-60 min), & potential symptombenefits based on published data. We asked: Based on the information provided, and ignoringprice or insurance coverage, if this medication were available how often would you use it whenyou have your IBS pain episodes? Options were: never, rarely, sometimes, most of the time& always. We dichotomized into willing (sometimes or greater) vs unwilling (never or rarely)to use ROSE-010. We performed t-tests comparing groups across severity metrics, includingIBSSS, severity numeric rating scale (NRS), pain NRS, pain episode frequency, work produc-tivity (WPAI), & HAD. Those willing to use rated the minimal pain (0-10 NRS) that wouldtrigger use. Results: Of 146 patients (age=42; 83% F; 16% IBS-C; 19% IBS-D; 65% IBS-M), the % never, rarely, sometimes, most of the time, and always willing to use were 19%,24%, 29%, 10%, & 17%. The table shows data for willing vs unwilling groups. Other thanHAD, all differences had p<0.05. Among those willing to use, the mean pain trigger was7.8+2. Conclusions: Over half of IBS patients in a clinical practice cohort are willing touse ROSE-010 for pain episodes. But pain must be severe (nearly 8/10) to justify use. Thosewilling to use have higher symptom severity, more severe and frequent pain episodes, andlower productivity, but no difference in anxiety or depression. This suggests that ROSE-010 may fulfill an unmet need for many IBS patients with impactful symptoms regardlessof psychological traits.Willing vs Unwilling to use ROSE-010
S1317
Investigation and Management of Irritable Bowel Syndrome in PrivatePractice: An AuditNicholas A. Kennedy, Marc F. LeMire, Alexander D. Rodgers, Peter A. Bampton
Introduction: Irritable bowel syndrome (IBS) is responsible for up to 50% of consultationswith gastroenterologists. This audit examines the manner in which it is investigated andmanaged in a large private practice. Methods: The electronic medical record system of theprivate practice was searched to to identify patients with a primary diagnosis of IBS. 557patients were found of which 150 were randomly chosen and assessed and 117 found tomeet inclusion criteria. The records of these patients were then reviewed retrospectively byan independent examiner (NK) and data regarding symptoms, investigation and managementwere recorded in a database. Data was then extracted from this database and analysed usinga spreadsheet. Results: The mean age of the 117 patients included in the detailed analysiswas 48.5 years, and 70.1% were female. Diarrhoea predominant IBS was themost representedsubtype of IBS (39.3%) of the total, with most of the remainder approximately equallydivided between constipation predominant, mixed and undetermined. Overall, 35.0% ofpatients met the Rome III criteria at the first visit, though this figure may reflect theretrospective nature of the data. Subsequent alternative diagnoses were made in 3 patients- lymphoma, ulcerative proctitis and infective colitis. None of these met Rome criteria andall had alarm features. The specialist requested one or more pathology tests for 54.7%of patients. 86.3% had one or more endoscopic procedures performed, most commonlycolonoscopy. In 92.3% of patients, the decision for or against colonoscopy was consistentwith the Gastroenterology Society of Australia guidelines. Only 4.5% of those having colonos-copy were recorded as having had a previous colonoscopy within the previous 5 years. Themost common abnormalities on colonoscopy were polyps, diverticulosis and haemorrhoids.Management approaches included dietary advice (43.9%), lifestyle advice (30.7%), antispas-modics (19.3%), fibre supplements (16.7%), neuromodulators (11.4%) and probiotics(7.0%). 13.2% were referred to a dietician, but only 2.5% to a psychologist. Conclusions:This audit provides an insight into real-life practice in the investigation and managementof IBS. It reveals a high rate for colonoscopy, suggesting that non-invasive modalities for
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