- Email: [email protected]
A randomized prospective comparison study of polyethylene glycol without electrolytes and milk of magnesia for children with constipation and encopresis
S1460
therapy; The STAI showed that anxiety-state as well as anmety-trait was lower after 8-week treatment, although changes were minor and similar for both treatments. According to patient's judgment treatment efficacy was excellent or good in 76% for levosulpiride and 77% for cisapride. Adverse effects related to medication were present in 13/69 (18.8%) cases in the levosulpiride group and in 8/71 (11.3%) cases in the cisapride group. Significantly (p = 0.03) more patients treated with cisapride had to abandon the trial because side effects. Conclusion: Levosulpinde is at least as effective as cisapride in the treatment of dysmotility-like functional dyspepsia being an attractive alternatzve.
Benefits and Risks of Pharmacotherapy for Irritable Bowel Syndrome (IBS): A Decision Analysis of Alosetron Use and Its Implications for Clinical Research Uri Ladabaum BACKGROUND: IBS causes substantial morbidity but not mortality. Alosetron may achieve "adequate relief' (AR) in diarrhea-predominant IBS (D-IBS) but it may cause major complications, including obstipation, ischemic colitis and death. The use of a potentially harmful drug for a non-lethal condition represents a therapeutic dilemma. AIMS: To appraise quantitatively the trade-off between possible symptomatic improvement and serious complications with alosetron treatment for D-IBS. METHODS: A decision analytic model was used to estimate quality-adjusted life-years (QALYs) and costs of an alosetron trial or standard treatment for 6 months in 45 year-old women with severe D-IBS. Alosetron was continued for 6 months only if AR was achieved after 4 weeks. Base case inputs included: AR in 28% of patients with standard treatment ($1/day) and 42% with alosetron ($4/day), reflecting a 14% therapeutic gain with alosetron (data from published trials); alosetron serious complication rate of 4/1,000 persons/6 months (cost up to $21,000 if surgery required) with 2% mortality given a serious complication (FDA data); D-IBS state utility of 0.674 (0=death; 1 = perfect health) and utility gain of 0.024 with AR (derived from published Short Form 36 data for IBS and a published regression equation); loss of 154 QALYs with a complicationrelated death (discounted life expectancy valued at D-IBS state utility). RESULTS: In the base case, alosetron's clinical benefit exceeded its risks, resulting in a gain of 0.00081 QALY/ person at a cost of $359,000/QALY gained. Alosetron's clinical benefit exceeded its risks (it gained QALYs) if the utility gain with AR was > 0 0 1 . A utility gain with AR of >0.08 was required for alosetron use to approach a cost of $50,000/QALY gained. In probabilistic analysis, alosetron gained QALYs in 98% of iterations at a median cost of $213,000/QALY gained (interquartile range $138,000-$339,000/QALY gained). The modePs results were highly sensitive to the utility gain with AR, alosetron's therapeutic gain and alosetron's complication rate. CONCLUSIONS: Alosetron's benefit-to-risk profile appears to be favorable, but its cost/QALY gained may be substantial. Decision analyses on IBS treatments are likely to be highly sensitive to the util W estimates used. There is a pressing need for future clinical research in the functional gastrointestinal disorders to make direct measurements of patients' preferences expressed as utilities.
$1463 A Randomized Prospective Comparison Study of Polyethylene Glycol without Electrolytes and Milk of Magnesia for Children with Constipation and Encopresis Vera Loening-Baucke, Dinesh S. Pashankar Introduction: Children with functional constipation and encopresis benefit from behavior modification and long-term daily laxatives. In this study, we determined the efficacy and patient acceptance of a new polyethylene glycol 3350 laxative without dectrolytes (PEG) as compared to milk of magnesia (MOM). Methods: 29 children (24 boys, mean age 7.3 + 2.6 years) with constipation and encopresis were randomized to treatment with either PEG or MOM mixed in the child's favored drink. All received behavior modification including toilet sitting after meals and filling out a daily stool diary. Children were rated as improved, if they had at least 3 bowel movements (BMs)/week with < 1 soiling/week and no abdominal pain. Results: Significant improvement was seen at the 1-momh and 3-month fofiow-ups in children receiving PEG (n= 14) and MOM (n= 15), see table. Children receiving PEG did as well as children on MOM at both follow-ups (p >0.1). Fourteen percent of children rated the PEG and 60% rated the MOM as bad tasting (p <0.03). This resulted in 3 children refusing to take the MOM at the 3-month follow-up with recurrence of symptoms in 2 At the 3-month follow-up, the mean dose of PEG was 0.6 -+ 0.3 g/kg body weight (range 021.1) and of MOM 1.0 _+ 0.7 ml/kg/body weight (range 0-2.6). Conclusions: The new PEG without electrolytes had similar efficacy as MOM, but was better accepted by the children with chronic cortsupation and encopresis. InlUal
1-moMh F/U
S1461
Frequencyof BMl#week: PEG
4~5
10 7*
7'4"
Effect of Corticotropin-releasing Hormone Receptor Antagonist on Autonomic Function in Irritable Bowel Syndrome Shin Fukudo, Yuko Shimada, Yasuhiro Sagami, fun Tayama, Michiko Kano, Mitoyori Kanazawa, Taisuke Nomura, Michio Hongo
MOM
3 ~3
11 , 5'
10 ~ 5*
Frequency of soiling/week: PEG
11 1 0
3 3*
2~3'
BOM
16 17
2 4"
1 1"
0% 0%
56%* 76%*
54%* 67%*
Children who improved: PEG MOM *differentto the initialdata, p <0.03
Background & Aims: Corticotropin-releasing hormone (CRH) is a major mediator of stress response. Previously we reported that patients with imtable bowel syndrome (IBS) have abnormal neuroendocnne response to CRH. IBS patients were also reported to have abnormal autonomic tone. We tested our hypothesis that autonomic function is changed by visceral stimulation and that this response is modified by CRH antagonist. Moreover, we predicted that this response is altered in IBS. Methods: Nine normal healthy subjects and 9 subjects diagnosed as IBS were studied. Diagnosis of IBS was based on Rome II criteria. The bag was inserted to the descending colon using colonoscopy Electrode was placed in the rectum under the X-ray fluoroscopy for visceral stimulation. ECG, blood pressure, plasma catecholamines, ACTH, and cortisol were measured during baseline, rectal electncal stimulation (ES), recovery', and colonic distention with the administration of saline. The same measurement was repeated after intravenous administration of 10 microg/Kg of alpha-helical CRH (ahCRH). Heart rate variability was evaluated with high frequency (HF, msec2) and low frequency (LF, msec2). Results: In controls, visceral stimulation induced significant reduction in HF (baseline 713 +/- 178 vs ES 458 +/- 111, p < 0.01, baseline vs distention 484 +/- 125, p < 0.01). Administration of ahCRH significamly reduced HF in controls (p < 0.01 ) and response above was diminished. By contrast, IBS patients showed significantly lower HE than controls (p < 0.05) and no significant changes in HF in response to visceral stimulation In IBS patients, ahCRH did not modified HF. Conclusions: These data suggest that vagal function is suppressed by visceral stimulation and that this response as well as basal vagal tone is suppressed by CRH antagomsm. Less response to CRH antagonist in IBS patients may be due to high endogenous CRH activity in IBS.
$1464
Improvement of Gastric Emptying in Patients with Diabetic Gastroparesis by Moxonidine Tibor Wittmann, Ildiko Kiss, Ferenc lzbeki, Andras 1. Rosztoczy, Tamas T. VarkonyL Rachard Roka, Janos Lonovics In patients with diabetic gastroparesis, clonidine treatment was associated with acceleration of gastric emptying. Clonidine, an alfa-2 adrenergic agonist, also has an affinity for imidazoline receptors. The role of moxonidine, a selective imidazoline receptor agonist, has not been investigated yet in patients with diabetic gastroparesis. The aim of our study was to investigate the effect of moxonidine in diabetic patients with delayed gastric emptying. Patients and methods: Ten diabetic patients with delayed gastric emptying and ten age matched apparently healthy subjects were enrolled in the study. The presence of cardiovascular autonomic neuropathy was investigated according to Ewings standard cardiovascular reflex tests. The mean age was 55 (31-76) years, the mean diabetes duration was 26 (10-51) years. The mean autonomic neuropathy score was 5.80 -+ 0 2 4 corresponding to a moderate autonomic neuropathy. Gastric emptying of a semisolid test meal (5g potato flakes in 400ml yogurt) was determined by ultrasonography in each patients prior to administration of moxonidine (0.2 mg Physiotens b.i.d.) and after one month of moxonidine treatment. Amral area was measured by 2D ultrasound probe. Measurements were done in the fasting state, immediately after the ingestion of the test meal (0ram) and then at 15, 30, 45, 60, 75, 90 minutes. Results: After one month moxonidine treatment, the antral area was significantly decreased from the 60th minute of the examination, compared to the values obtained before treatment and appeared to be similar to the control values. Conclusion: The imidazoline receptor agonist moxoindme seems to be a promising new agent in the treatment of diabetic gastroparesis. (grant support: ETT 543-02/2000).
S1462
Levosulpiride in the Treatment of Dysmotility-Like Functional Dyspepsia: Randomised Double-Dimmed Comparison with Cisapride Fermin Meann, Luis Rodngo, Arturo Perez-Mota, Agustin Balboa, Isabel Jimenez, JuanJose Sebastian, Caro Paton Background: Functional dyspepsia treatment continues to be a clinical challenge. Cisaprlde has been the most used drug and with more consistent results, but cardiac adverse effects precluded its utilization. Levosulpinde is a benzamide denvate D2 dopamme antagonist with prokinetic activity able to accelerate gastric emptying and increase the discomfort threshold to gastric distension. Aim: To investigate the clinical efficacy of levosulpiride in patients with dysmotiflty-like functional dyspepsia. Methods: In a muhicentnc randomized double-dimmed trial we compare the effects of 8-week treatmerlt either with levosulpiride 25 mg t.d.s. (n=69) or with cisapride 10 mg t.d.s (n=71). Individual symptoms (pain/ discomfort, fullness, bloating, early satiety and nausea/vomiting), the dyspepsia global symptom score (sum of different symptoms), effect on health related quality of life (Nottingham Health Profile: NHP) and the anxiogenic situation (State-Trait Anxiety Inventory: STAI) were evaluated; adverse events were also recorded. Results: Both levosulpiride and cisapride improved dyspeptic symptoms and decreased the total symptom score (-79.9% and -71.3%, respectively'); no significant statistical differences was achieved but there was a trend in favor of levosulpiride (p = 007). Health related quality of life and anxiety improved similarly after both treatments: The NHP showed that global improvement was 37.5% for levosulpiride and 408% for cisapride and that all six health dimensions had improved after 8-week
AGA Abstracts
3-moth F/U
A-222
therapy; The STAI showed that anxiety-state as well as anmety-trait was lower after 8-week treatment, although changes were minor and similar for both treatments. According to patient's judgment treatment efficacy was excellent or good in 76% for levosulpiride and 77% for cisapride. Adverse effects related to medication were present in 13/69 (18.8%) cases in the levosulpiride group and in 8/71 (11.3%) cases in the cisapride group. Significantly (p = 0.03) more patients treated with cisapride had to abandon the trial because side effects. Conclusion: Levosulpinde is at least as effective as cisapride in the treatment of dysmotility-like functional dyspepsia being an attractive alternatzve.
Benefits and Risks of Pharmacotherapy for Irritable Bowel Syndrome (IBS): A Decision Analysis of Alosetron Use and Its Implications for Clinical Research Uri Ladabaum BACKGROUND: IBS causes substantial morbidity but not mortality. Alosetron may achieve "adequate relief' (AR) in diarrhea-predominant IBS (D-IBS) but it may cause major complications, including obstipation, ischemic colitis and death. The use of a potentially harmful drug for a non-lethal condition represents a therapeutic dilemma. AIMS: To appraise quantitatively the trade-off between possible symptomatic improvement and serious complications with alosetron treatment for D-IBS. METHODS: A decision analytic model was used to estimate quality-adjusted life-years (QALYs) and costs of an alosetron trial or standard treatment for 6 months in 45 year-old women with severe D-IBS. Alosetron was continued for 6 months only if AR was achieved after 4 weeks. Base case inputs included: AR in 28% of patients with standard treatment ($1/day) and 42% with alosetron ($4/day), reflecting a 14% therapeutic gain with alosetron (data from published trials); alosetron serious complication rate of 4/1,000 persons/6 months (cost up to $21,000 if surgery required) with 2% mortality given a serious complication (FDA data); D-IBS state utility of 0.674 (0=death; 1 = perfect health) and utility gain of 0.024 with AR (derived from published Short Form 36 data for IBS and a published regression equation); loss of 154 QALYs with a complicationrelated death (discounted life expectancy valued at D-IBS state utility). RESULTS: In the base case, alosetron's clinical benefit exceeded its risks, resulting in a gain of 0.00081 QALY/ person at a cost of $359,000/QALY gained. Alosetron's clinical benefit exceeded its risks (it gained QALYs) if the utility gain with AR was > 0 0 1 . A utility gain with AR of >0.08 was required for alosetron use to approach a cost of $50,000/QALY gained. In probabilistic analysis, alosetron gained QALYs in 98% of iterations at a median cost of $213,000/QALY gained (interquartile range $138,000-$339,000/QALY gained). The modePs results were highly sensitive to the utility gain with AR, alosetron's therapeutic gain and alosetron's complication rate. CONCLUSIONS: Alosetron's benefit-to-risk profile appears to be favorable, but its cost/QALY gained may be substantial. Decision analyses on IBS treatments are likely to be highly sensitive to the util W estimates used. There is a pressing need for future clinical research in the functional gastrointestinal disorders to make direct measurements of patients' preferences expressed as utilities.
$1463 A Randomized Prospective Comparison Study of Polyethylene Glycol without Electrolytes and Milk of Magnesia for Children with Constipation and Encopresis Vera Loening-Baucke, Dinesh S. Pashankar Introduction: Children with functional constipation and encopresis benefit from behavior modification and long-term daily laxatives. In this study, we determined the efficacy and patient acceptance of a new polyethylene glycol 3350 laxative without dectrolytes (PEG) as compared to milk of magnesia (MOM). Methods: 29 children (24 boys, mean age 7.3 + 2.6 years) with constipation and encopresis were randomized to treatment with either PEG or MOM mixed in the child's favored drink. All received behavior modification including toilet sitting after meals and filling out a daily stool diary. Children were rated as improved, if they had at least 3 bowel movements (BMs)/week with < 1 soiling/week and no abdominal pain. Results: Significant improvement was seen at the 1-momh and 3-month fofiow-ups in children receiving PEG (n= 14) and MOM (n= 15), see table. Children receiving PEG did as well as children on MOM at both follow-ups (p >0.1). Fourteen percent of children rated the PEG and 60% rated the MOM as bad tasting (p <0.03). This resulted in 3 children refusing to take the MOM at the 3-month follow-up with recurrence of symptoms in 2 At the 3-month follow-up, the mean dose of PEG was 0.6 -+ 0.3 g/kg body weight (range 021.1) and of MOM 1.0 _+ 0.7 ml/kg/body weight (range 0-2.6). Conclusions: The new PEG without electrolytes had similar efficacy as MOM, but was better accepted by the children with chronic cortsupation and encopresis. InlUal
1-moMh F/U
S1461
Frequencyof BMl#week: PEG
4~5
10 7*
7'4"
Effect of Corticotropin-releasing Hormone Receptor Antagonist on Autonomic Function in Irritable Bowel Syndrome Shin Fukudo, Yuko Shimada, Yasuhiro Sagami, fun Tayama, Michiko Kano, Mitoyori Kanazawa, Taisuke Nomura, Michio Hongo
MOM
3 ~3
11 , 5'
10 ~ 5*
Frequency of soiling/week: PEG
11 1 0
3 3*
2~3'
BOM
16 17
2 4"
1 1"
0% 0%
56%* 76%*
54%* 67%*
Children who improved: PEG MOM *differentto the initialdata, p <0.03
Background & Aims: Corticotropin-releasing hormone (CRH) is a major mediator of stress response. Previously we reported that patients with imtable bowel syndrome (IBS) have abnormal neuroendocnne response to CRH. IBS patients were also reported to have abnormal autonomic tone. We tested our hypothesis that autonomic function is changed by visceral stimulation and that this response is modified by CRH antagonist. Moreover, we predicted that this response is altered in IBS. Methods: Nine normal healthy subjects and 9 subjects diagnosed as IBS were studied. Diagnosis of IBS was based on Rome II criteria. The bag was inserted to the descending colon using colonoscopy Electrode was placed in the rectum under the X-ray fluoroscopy for visceral stimulation. ECG, blood pressure, plasma catecholamines, ACTH, and cortisol were measured during baseline, rectal electncal stimulation (ES), recovery', and colonic distention with the administration of saline. The same measurement was repeated after intravenous administration of 10 microg/Kg of alpha-helical CRH (ahCRH). Heart rate variability was evaluated with high frequency (HF, msec2) and low frequency (LF, msec2). Results: In controls, visceral stimulation induced significant reduction in HF (baseline 713 +/- 178 vs ES 458 +/- 111, p < 0.01, baseline vs distention 484 +/- 125, p < 0.01). Administration of ahCRH significamly reduced HF in controls (p < 0.01 ) and response above was diminished. By contrast, IBS patients showed significantly lower HE than controls (p < 0.05) and no significant changes in HF in response to visceral stimulation In IBS patients, ahCRH did not modified HF. Conclusions: These data suggest that vagal function is suppressed by visceral stimulation and that this response as well as basal vagal tone is suppressed by CRH antagomsm. Less response to CRH antagonist in IBS patients may be due to high endogenous CRH activity in IBS.
$1464
Improvement of Gastric Emptying in Patients with Diabetic Gastroparesis by Moxonidine Tibor Wittmann, Ildiko Kiss, Ferenc lzbeki, Andras 1. Rosztoczy, Tamas T. VarkonyL Rachard Roka, Janos Lonovics In patients with diabetic gastroparesis, clonidine treatment was associated with acceleration of gastric emptying. Clonidine, an alfa-2 adrenergic agonist, also has an affinity for imidazoline receptors. The role of moxonidine, a selective imidazoline receptor agonist, has not been investigated yet in patients with diabetic gastroparesis. The aim of our study was to investigate the effect of moxonidine in diabetic patients with delayed gastric emptying. Patients and methods: Ten diabetic patients with delayed gastric emptying and ten age matched apparently healthy subjects were enrolled in the study. The presence of cardiovascular autonomic neuropathy was investigated according to Ewings standard cardiovascular reflex tests. The mean age was 55 (31-76) years, the mean diabetes duration was 26 (10-51) years. The mean autonomic neuropathy score was 5.80 -+ 0 2 4 corresponding to a moderate autonomic neuropathy. Gastric emptying of a semisolid test meal (5g potato flakes in 400ml yogurt) was determined by ultrasonography in each patients prior to administration of moxonidine (0.2 mg Physiotens b.i.d.) and after one month of moxonidine treatment. Amral area was measured by 2D ultrasound probe. Measurements were done in the fasting state, immediately after the ingestion of the test meal (0ram) and then at 15, 30, 45, 60, 75, 90 minutes. Results: After one month moxonidine treatment, the antral area was significantly decreased from the 60th minute of the examination, compared to the values obtained before treatment and appeared to be similar to the control values. Conclusion: The imidazoline receptor agonist moxoindme seems to be a promising new agent in the treatment of diabetic gastroparesis. (grant support: ETT 543-02/2000).
S1462
Levosulpiride in the Treatment of Dysmotility-Like Functional Dyspepsia: Randomised Double-Dimmed Comparison with Cisapride Fermin Meann, Luis Rodngo, Arturo Perez-Mota, Agustin Balboa, Isabel Jimenez, JuanJose Sebastian, Caro Paton Background: Functional dyspepsia treatment continues to be a clinical challenge. Cisaprlde has been the most used drug and with more consistent results, but cardiac adverse effects precluded its utilization. Levosulpinde is a benzamide denvate D2 dopamme antagonist with prokinetic activity able to accelerate gastric emptying and increase the discomfort threshold to gastric distension. Aim: To investigate the clinical efficacy of levosulpiride in patients with dysmotiflty-like functional dyspepsia. Methods: In a muhicentnc randomized double-dimmed trial we compare the effects of 8-week treatmerlt either with levosulpiride 25 mg t.d.s. (n=69) or with cisapride 10 mg t.d.s (n=71). Individual symptoms (pain/ discomfort, fullness, bloating, early satiety and nausea/vomiting), the dyspepsia global symptom score (sum of different symptoms), effect on health related quality of life (Nottingham Health Profile: NHP) and the anxiogenic situation (State-Trait Anxiety Inventory: STAI) were evaluated; adverse events were also recorded. Results: Both levosulpiride and cisapride improved dyspeptic symptoms and decreased the total symptom score (-79.9% and -71.3%, respectively'); no significant statistical differences was achieved but there was a trend in favor of levosulpiride (p = 007). Health related quality of life and anxiety improved similarly after both treatments: The NHP showed that global improvement was 37.5% for levosulpiride and 408% for cisapride and that all six health dimensions had improved after 8-week
AGA Abstracts
3-moth F/U
A-222