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Mo2090 Gastric Emptying, Glycemia, and Upper GI Symptoms Are Independent Factors in Diabetic Gastroparesis
Mo2091
Modeling Equations for Prediction of Improvement in Patients With Gastroparesis Based on 48 Week Prospective Outcome Data Pankaj J. Pasricha, Katherine P. Yates, Henry P. Parkman, Linda Anh B. Nguyen, William J. Snape, Thomas L. Abell, Richard W. McCallum, Irene Sarosiek, William L. Hasler, Kenneth L. Koch, Gianrico Farrugia, Aynur Unalp, Frank A. Hamilton, James Tonascia, GpCRC Consortium
Gastric Emptying, Glycemia, and Upper GI Symptoms Are Independent Factors in Diabetic Gastroparesis Niels Ejskjaer, John M. Wo, Tuba Esfandyari, M. Mazen Jamal, Georg Dimcevski, Lise Tarnow, Rayaz Malik, Per M. Hellström, Elsa Mondou, Joe Quinn, Franck Rousseau, Richard W. McCallum Introduction: Whilst symptomatic improvement in diabetic gastroparesis has been observed in a 28-day Phase 2a study of TZP-102 a novel ghrelin agonist (Ejsjkjaer et al., ADA 2012), as reported in other publications (e.g., Pasricha et al., 2011) gastric emptying dynamics have shown little apparent inter-relationship. Aim: To assess if symptoms and glycemia had any correlation with gastric emptying overall and in a subgroup of patients with symptomatic diabetic gastroparesis and severely delayed gastric emptying at baseline. Methods: TZP-102 was evaluated in a double-blind, randomized study in patients with type 1 or 2 diabetes mellitus with gastric half-emptying time (T1/2) by breath test (BT) ≥ 150 minutes and symptoms of gastroparesis for at least 3 months. Patients were treated 1:1:1:1 with placebo, 10, 20, or 40 mg TZP-102 once daily for 28 days. A 4-symptom PAGI-SYM composite score for a subset of 4 main symptoms (nausea, early satiety, bloating, and upper abdominal pain) was analyzed. Gastric half-emptying time (T1/2) was measured pretreatment and at Day 28. Overall linear regression (all patients) was performed and the subset of patients with pretreatment T1/2≥ 168 minutes mean +2SD and the subset of patients with pre-BT glucose ,250 mg/dL were analyzed. Results: 92 diabetic patients (females 65%; age 49.9±11.9 years; 91% Caucasians; 60% type 1 diabetes; HbA1c 8.3±1.5 %; GCSI 3.3±0.8; BT T1/2 193±51 min) received study treatment (22, 21, 23 and 26 patients received 10, 20, 40 mg TZP-102 and placebo, respectively). The results in both subsets were the same as for the overall study with no correlation between the severity of the symptoms or the level of glycemia, and the gastric emptying T1/2 for TZP-102 active arms and the placebo arm at baseline or at the end of therapy. Linear regression analyses showed no correlation between absolute blood glucose values at the time of BT and gastric T1/2. Figures 1 and 2 are illustrative. TZP-102 was well tolerated. Conclusions: 1) Ghrelin agonist TZP-102, an oral once daily treatment, had a good safety profile in diabetic patients with gastroparesis; 2) In a subset analysis based on blood glucose and gastric T1/2 thresholds the outcome was similar to the overall results; 3) There was no correlation between change in gastric emptying during therapy and change in the severity of symptoms, suggesting that these can be independent events in diabetic gastroparesis; 4) Gastric emptying has been correlated with glycemia in healthy subjects, but this correlation was not be observed in diabetic gastroparesis patients within the context of the glucose ranges in this study.
Background. The management of patients with gastroparesis remains challenging in many ways including an inability to project the course of the disease in a given patient. In this study, our aim was to determine if how well statistical models can confidently predict symptomatic improvement after a year of standard of care medical treatment. Methods. We studied 358 patients with gastroparesis (including idiopathic as well as that associated with both type 1 and type 2 diabetes mellitus) enrolled in the NIDDK Gastroparesis Clinical Research Consortium (GpCRC) registry. We used logistic regression modeling to determine the degree to which initial characteristics predict symptomatic improvement after 48 weeks of standard of care medical treatment with visits at least every 16 weeks and prescribed medications or other therapies as per the judgment of the treating physician. Improvement was defined as a decline of at least 1 point in the GCSI scores at 48 weeks compared to the baseline score. Regression coefficients, 95% CIs, P-values and areas under the ROC were used to compare a comprehensive model with baseline characteristics such as symptom scores, demographics, lifestyle, gastric emptying, medical history and psychological quality of life (QOL) as predictors vs. a much smaller reduced model (derived using stepwise regression), using only baseline characteristics. Results. Both the comprehensive model and reduced models predicted improvement well (AUROCs .0.70) and there was no significant difference in predictive ability of the smaller model compared to the comprehensive model (P=0.11). See Table 1 for the coefficients, CIs, and P-values and the logistic equation used to predict improvement; see Figure 1 for the ROC comparisons. Conclusions: It is possible to construct a robust predictive equation that identifies patients with gastroparesis that are likely to improve after a year of follow-up, but better models are needed to more fully facilitate counseling of patients as well as top generate hypothesis for interventions to improve outcomes in future studies.
Figure 1. Linear Regression 4-Symptom PAGI Composite versus GMBT T1/2
S-739
AGA Abstracts
AGA Abstracts
Mo2090
Modeling Equations for Prediction of Improvement in Patients With Gastroparesis Based on 48 Week Prospective Outcome Data Pankaj J. Pasricha, Katherine P. Yates, Henry P. Parkman, Linda Anh B. Nguyen, William J. Snape, Thomas L. Abell, Richard W. McCallum, Irene Sarosiek, William L. Hasler, Kenneth L. Koch, Gianrico Farrugia, Aynur Unalp, Frank A. Hamilton, James Tonascia, GpCRC Consortium
Gastric Emptying, Glycemia, and Upper GI Symptoms Are Independent Factors in Diabetic Gastroparesis Niels Ejskjaer, John M. Wo, Tuba Esfandyari, M. Mazen Jamal, Georg Dimcevski, Lise Tarnow, Rayaz Malik, Per M. Hellström, Elsa Mondou, Joe Quinn, Franck Rousseau, Richard W. McCallum Introduction: Whilst symptomatic improvement in diabetic gastroparesis has been observed in a 28-day Phase 2a study of TZP-102 a novel ghrelin agonist (Ejsjkjaer et al., ADA 2012), as reported in other publications (e.g., Pasricha et al., 2011) gastric emptying dynamics have shown little apparent inter-relationship. Aim: To assess if symptoms and glycemia had any correlation with gastric emptying overall and in a subgroup of patients with symptomatic diabetic gastroparesis and severely delayed gastric emptying at baseline. Methods: TZP-102 was evaluated in a double-blind, randomized study in patients with type 1 or 2 diabetes mellitus with gastric half-emptying time (T1/2) by breath test (BT) ≥ 150 minutes and symptoms of gastroparesis for at least 3 months. Patients were treated 1:1:1:1 with placebo, 10, 20, or 40 mg TZP-102 once daily for 28 days. A 4-symptom PAGI-SYM composite score for a subset of 4 main symptoms (nausea, early satiety, bloating, and upper abdominal pain) was analyzed. Gastric half-emptying time (T1/2) was measured pretreatment and at Day 28. Overall linear regression (all patients) was performed and the subset of patients with pretreatment T1/2≥ 168 minutes mean +2SD and the subset of patients with pre-BT glucose ,250 mg/dL were analyzed. Results: 92 diabetic patients (females 65%; age 49.9±11.9 years; 91% Caucasians; 60% type 1 diabetes; HbA1c 8.3±1.5 %; GCSI 3.3±0.8; BT T1/2 193±51 min) received study treatment (22, 21, 23 and 26 patients received 10, 20, 40 mg TZP-102 and placebo, respectively). The results in both subsets were the same as for the overall study with no correlation between the severity of the symptoms or the level of glycemia, and the gastric emptying T1/2 for TZP-102 active arms and the placebo arm at baseline or at the end of therapy. Linear regression analyses showed no correlation between absolute blood glucose values at the time of BT and gastric T1/2. Figures 1 and 2 are illustrative. TZP-102 was well tolerated. Conclusions: 1) Ghrelin agonist TZP-102, an oral once daily treatment, had a good safety profile in diabetic patients with gastroparesis; 2) In a subset analysis based on blood glucose and gastric T1/2 thresholds the outcome was similar to the overall results; 3) There was no correlation between change in gastric emptying during therapy and change in the severity of symptoms, suggesting that these can be independent events in diabetic gastroparesis; 4) Gastric emptying has been correlated with glycemia in healthy subjects, but this correlation was not be observed in diabetic gastroparesis patients within the context of the glucose ranges in this study.
Background. The management of patients with gastroparesis remains challenging in many ways including an inability to project the course of the disease in a given patient. In this study, our aim was to determine if how well statistical models can confidently predict symptomatic improvement after a year of standard of care medical treatment. Methods. We studied 358 patients with gastroparesis (including idiopathic as well as that associated with both type 1 and type 2 diabetes mellitus) enrolled in the NIDDK Gastroparesis Clinical Research Consortium (GpCRC) registry. We used logistic regression modeling to determine the degree to which initial characteristics predict symptomatic improvement after 48 weeks of standard of care medical treatment with visits at least every 16 weeks and prescribed medications or other therapies as per the judgment of the treating physician. Improvement was defined as a decline of at least 1 point in the GCSI scores at 48 weeks compared to the baseline score. Regression coefficients, 95% CIs, P-values and areas under the ROC were used to compare a comprehensive model with baseline characteristics such as symptom scores, demographics, lifestyle, gastric emptying, medical history and psychological quality of life (QOL) as predictors vs. a much smaller reduced model (derived using stepwise regression), using only baseline characteristics. Results. Both the comprehensive model and reduced models predicted improvement well (AUROCs .0.70) and there was no significant difference in predictive ability of the smaller model compared to the comprehensive model (P=0.11). See Table 1 for the coefficients, CIs, and P-values and the logistic equation used to predict improvement; see Figure 1 for the ROC comparisons. Conclusions: It is possible to construct a robust predictive equation that identifies patients with gastroparesis that are likely to improve after a year of follow-up, but better models are needed to more fully facilitate counseling of patients as well as top generate hypothesis for interventions to improve outcomes in future studies.
Figure 1. Linear Regression 4-Symptom PAGI Composite versus GMBT T1/2
S-739
AGA Abstracts
AGA Abstracts
Mo2090