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Mo1582 Domperidone to Treat Symptoms of Gastroparesis: Benefits and Risks From a Large Single Center Cohort
Mo1582
Table 1: Discriptive statistics for Baseline Insulin, Amylin and Gp symptom scores in Gp patients
Domperidone to Treat Symptoms of Gastroparesis: Benefits and Risks From a Large Single Center Cohort Ron Schey, Mohammed Saadi, Deena Midani, Aaron Roberts, Henry P. Parkman
AGA Abstracts
Domperidone is used to treat refractory symptoms of gastroparesis. Despite initial favorable results reported with domperidone, this agent was not approved by the Federal Drug Administration (FDA). However, treatment with domperidone can occur using the FDA investigator new drug (IND) program. In the last year, there has been increased awareness about domperidone side effects, especially cardiac side effects. Aim: To report our experience with domperidone for refractory gastroparesis in an academic medical center. We wanted to describe the outcome of starting patients on domperidone; specifically efficacy, symptom improvements, and side effects. Methods: Domperidone was prescribed to patients with refractory gastroparesis under a FDA IND and IRB protocol assessing symptoms and side effects with EKG, potassium, magnesium monitoring. Patients were treated with 10 mg QID or TID with follow up at 2-3 months. Patients filled out Patient Assessment of Upper GI Symptoms (PAGI-SYM) assessing symptom severity on a 5 point scale prior to treatment and at follow up along with Clinical Patient Grading Assessment Scale (CPGAS, +7=completely better; 0=no change;-7=very much worse). Results: Of 125 patients initially prescribed domperidone for refractory symptoms of gastroparesis from July 2014 to October 2015, 7 did not take this medication and 3 were lost to follow-up. Of the 115 known patients treated with domperidone (age 41±17 years, 104 female, BMI 24±8), 88 had idiopathic gastroparesis, 16 diabetic gastroparesis, and 9 postsurgical gastroparesis. Gastric emptying showed 28±22% retention at 4 hours. 5 patients had gastric stimulators, 6 with G and/or J tubes, and 1 on TPN. During treatment, side effects were reported by 44 patients (most common - headache, tachycardia/palpitations, diarrhea), of which 14 patients stopped treatment. 101 patients were seen at their follow-up visit taking domperidone (2.4±2.7 months after starting treatment, average dose 36±13 mg/day). The CPGAS averaged 2.7±2.7 (p<0.01 vs 0) with 69 patients reporting symptom improvement and 45 patients at least moderately improved with CPGAS>4. Improvements were seen in most symptoms, especially postprandial fullness (decrease in severity score of 1.1), nausea (1.0), vomiting (1.0), stomach fullness (1.0). Conclusions: In this large single center cohort study of gastroparesis patients treated with domperidone, side effects necessitating discontinuing treatment occurred in 14 of 115 patients (12%). The majority of patients remaining on treatment (69 of 101 patients; 68%) experienced an improvement in symptoms of gastroparesis, with 45 of 101 (45%) at least moderately improved. Symptoms especially improved were postprandial fullness, nausea, vomiting, and stomach fullness. Thus, this study reports benefit and risk information helpful to physicians and patients contemplating use of domperidone.
*Results reported as Means ± Std Dev (UCI, LCI) Table 2: Serum Insulin and Active Amylin level and associations with Gp symptoms of Bloating and Anorexia
Mo1583 Dysregulation of Hormones Insulin and Amylin Is Associated With the Symptoms of Bloating and Anorexia in Diabetic Gastroparesis Archana Kedar, Shifat Ahmed, Chirag M. Patel, Abigail Stocker, Lindsay McElmurray, Michael G. Hughes, Karen Beatty, Teresa Cutts, Mohammad K. Mohammad, Keith C. Falkner, Thomas L. Abell Background: Gastrointestinal Symptoms (Sx) generation is an extremely complex multifactorial pathophysiological process and dependent on gut biomass, quality of food, motility factors and enteric hormones. Bloating as experienced by patients is explained as a sense of fullness or abdominal distension and may be extremely hard to treat. Patients with gastric dysmotility often report bloating and anorexia as the initial and most common Sx at the onset of their disorder. Aim: In this study we explored the role of enteric hormones insulin, glucagon, amylin, ghrelin and leptin with the spectrum of Sx of Gastroparesis (Gp) including nausea, vomiting, bloating, satiety and anorexia. Methods: 43 patients with the Sx of Gp were enrolled in a prospective study, with 23 being Diabetic (DM type1=37%) and 20 Idiopathic Gp (IDGp). Average age was 46 years, 65% females and 81% Caucasian. Baseline serum hormone levels of insulin, glucagon, amylin, ghrelin and leptin were measured using Millipore Milliplex Assay LUMINEX- ELISA. Gp Sx were recorded using two scales: Gp Cardinal Symptom Index (GCSI) and Patient Related Outcome (PRO) scales. Relationships were reported as slope, CI and p values and other results were reported as means, SD and CIs. Results: Serum insulin showed significant associations with the Gp Sx of bloating in DMGp group using both the GCSI scale (0.0003 (0.0004, 0.0006) p = 0.027) and PRO scale (0.0002 (3.43e06, 0.0004) p = 0.046. Similar associations were noted with amylin and bloating Sx, in addition associations were also noted with Gp Sx anorexia with PRO Scale (0.010 (0.004, 0.016) p = 0.002) (Table 1,2) Conclusion: Levels of insulin and amylin correlated directly with the Gp Sx of bloating and anorexia using 2 commonly used scales. As these are commonly reported initial Sx by Gp patients, the role of the pancreatic islets function in glucose homeostasis and onset of bloating warrants further investigation.
* Results reported as Slope (UCI, LCI) p value
Mo1584 Energy of Gastric Electrical Stimulation Interacts With Cajal, Mast and S100 Cells to Predict GI Symptom Outcome Nikhil Kadle, Christina Pinkston, Guy Brock, Xiu Yang, Abigail Stocker, Lindsay McElmurray, Angel Munoz, Siva R. Cheetirala, Malathi L. Perugula, Michael G. Hughes, Mostafa Fraig, Warren Starkebaum, Thomas L. Abell Introduction: Gastric electrical stimulation (GES) has been applied without consideration of energy delivered to cells involved in the enteric nervous system (ENS). Prior data showed energy requirements for GES may vary in terms of individualized patient symptom relief (NGM 2006, 18(4) 334-338). Interstitial Cells of Cajal (ICC) disruption results in abnormalities in slow-wave initiation and conduction in gastroparesis (Gp), but other cell types may be important in response to GES. We hypothesized energy delivered relative to the number of cells on full thickness biopsy (FTB) is related to symptom outcome. Patients: 38 patients [12 male, 26 female, mean age 43.9 years, 31 Caucasian, Dx: 19 diabetic (DM), 19 idiopathic (ID)] were studied at baseline, and after temporary GES (tGES) placement for symptoms of Gp as described (GIE 74: 496-503). Methods: Patients were studied at baseline, after tGES placement with standardized symptom scores (Sx) using a patient reported outcome (PRO) diary and solid/liquid gastric emptying time. Energy parameters were calculated as charge/ pulse, energy/pulse, power/pulse and average power using electrical engineering formulas. FTBs were obtained at subsequent permanent GES implantation and analyzed for CD117/ Cajal, S100 and Mast cells per high-power field (hpf). We compared energy parameters and cells (product of energy parameters and cell density) from FTBs to results of Gp Sx after tGES by Wilcoxon 2 sample tests and Spearman correlations reported as mean (SD). Results: Table 1 shows number of cells by energy metric and diabetic status. Number of cells/hpf for inner (p=0.02) and outer layers (p<0.001) of mast cells for DM vs ID were significantly different. Charge of outer layer of mast cells in DM vs ID was significantly different (p<0.001). In outer layer of mast cells, energy, power and average power parameters in DM vs ID were significantly different (p=0.03). Charge in inner layer of S100 cells in DM vs ID (p<0.02) was significantly different. No significant difference in cells or energy parameters in ICC for
S-719
AGA Abstracts
Table 1: Discriptive statistics for Baseline Insulin, Amylin and Gp symptom scores in Gp patients
Domperidone to Treat Symptoms of Gastroparesis: Benefits and Risks From a Large Single Center Cohort Ron Schey, Mohammed Saadi, Deena Midani, Aaron Roberts, Henry P. Parkman
AGA Abstracts
Domperidone is used to treat refractory symptoms of gastroparesis. Despite initial favorable results reported with domperidone, this agent was not approved by the Federal Drug Administration (FDA). However, treatment with domperidone can occur using the FDA investigator new drug (IND) program. In the last year, there has been increased awareness about domperidone side effects, especially cardiac side effects. Aim: To report our experience with domperidone for refractory gastroparesis in an academic medical center. We wanted to describe the outcome of starting patients on domperidone; specifically efficacy, symptom improvements, and side effects. Methods: Domperidone was prescribed to patients with refractory gastroparesis under a FDA IND and IRB protocol assessing symptoms and side effects with EKG, potassium, magnesium monitoring. Patients were treated with 10 mg QID or TID with follow up at 2-3 months. Patients filled out Patient Assessment of Upper GI Symptoms (PAGI-SYM) assessing symptom severity on a 5 point scale prior to treatment and at follow up along with Clinical Patient Grading Assessment Scale (CPGAS, +7=completely better; 0=no change;-7=very much worse). Results: Of 125 patients initially prescribed domperidone for refractory symptoms of gastroparesis from July 2014 to October 2015, 7 did not take this medication and 3 were lost to follow-up. Of the 115 known patients treated with domperidone (age 41±17 years, 104 female, BMI 24±8), 88 had idiopathic gastroparesis, 16 diabetic gastroparesis, and 9 postsurgical gastroparesis. Gastric emptying showed 28±22% retention at 4 hours. 5 patients had gastric stimulators, 6 with G and/or J tubes, and 1 on TPN. During treatment, side effects were reported by 44 patients (most common - headache, tachycardia/palpitations, diarrhea), of which 14 patients stopped treatment. 101 patients were seen at their follow-up visit taking domperidone (2.4±2.7 months after starting treatment, average dose 36±13 mg/day). The CPGAS averaged 2.7±2.7 (p<0.01 vs 0) with 69 patients reporting symptom improvement and 45 patients at least moderately improved with CPGAS>4. Improvements were seen in most symptoms, especially postprandial fullness (decrease in severity score of 1.1), nausea (1.0), vomiting (1.0), stomach fullness (1.0). Conclusions: In this large single center cohort study of gastroparesis patients treated with domperidone, side effects necessitating discontinuing treatment occurred in 14 of 115 patients (12%). The majority of patients remaining on treatment (69 of 101 patients; 68%) experienced an improvement in symptoms of gastroparesis, with 45 of 101 (45%) at least moderately improved. Symptoms especially improved were postprandial fullness, nausea, vomiting, and stomach fullness. Thus, this study reports benefit and risk information helpful to physicians and patients contemplating use of domperidone.
*Results reported as Means ± Std Dev (UCI, LCI) Table 2: Serum Insulin and Active Amylin level and associations with Gp symptoms of Bloating and Anorexia
Mo1583 Dysregulation of Hormones Insulin and Amylin Is Associated With the Symptoms of Bloating and Anorexia in Diabetic Gastroparesis Archana Kedar, Shifat Ahmed, Chirag M. Patel, Abigail Stocker, Lindsay McElmurray, Michael G. Hughes, Karen Beatty, Teresa Cutts, Mohammad K. Mohammad, Keith C. Falkner, Thomas L. Abell Background: Gastrointestinal Symptoms (Sx) generation is an extremely complex multifactorial pathophysiological process and dependent on gut biomass, quality of food, motility factors and enteric hormones. Bloating as experienced by patients is explained as a sense of fullness or abdominal distension and may be extremely hard to treat. Patients with gastric dysmotility often report bloating and anorexia as the initial and most common Sx at the onset of their disorder. Aim: In this study we explored the role of enteric hormones insulin, glucagon, amylin, ghrelin and leptin with the spectrum of Sx of Gastroparesis (Gp) including nausea, vomiting, bloating, satiety and anorexia. Methods: 43 patients with the Sx of Gp were enrolled in a prospective study, with 23 being Diabetic (DM type1=37%) and 20 Idiopathic Gp (IDGp). Average age was 46 years, 65% females and 81% Caucasian. Baseline serum hormone levels of insulin, glucagon, amylin, ghrelin and leptin were measured using Millipore Milliplex Assay LUMINEX- ELISA. Gp Sx were recorded using two scales: Gp Cardinal Symptom Index (GCSI) and Patient Related Outcome (PRO) scales. Relationships were reported as slope, CI and p values and other results were reported as means, SD and CIs. Results: Serum insulin showed significant associations with the Gp Sx of bloating in DMGp group using both the GCSI scale (0.0003 (0.0004, 0.0006) p = 0.027) and PRO scale (0.0002 (3.43e06, 0.0004) p = 0.046. Similar associations were noted with amylin and bloating Sx, in addition associations were also noted with Gp Sx anorexia with PRO Scale (0.010 (0.004, 0.016) p = 0.002) (Table 1,2) Conclusion: Levels of insulin and amylin correlated directly with the Gp Sx of bloating and anorexia using 2 commonly used scales. As these are commonly reported initial Sx by Gp patients, the role of the pancreatic islets function in glucose homeostasis and onset of bloating warrants further investigation.
* Results reported as Slope (UCI, LCI) p value
Mo1584 Energy of Gastric Electrical Stimulation Interacts With Cajal, Mast and S100 Cells to Predict GI Symptom Outcome Nikhil Kadle, Christina Pinkston, Guy Brock, Xiu Yang, Abigail Stocker, Lindsay McElmurray, Angel Munoz, Siva R. Cheetirala, Malathi L. Perugula, Michael G. Hughes, Mostafa Fraig, Warren Starkebaum, Thomas L. Abell Introduction: Gastric electrical stimulation (GES) has been applied without consideration of energy delivered to cells involved in the enteric nervous system (ENS). Prior data showed energy requirements for GES may vary in terms of individualized patient symptom relief (NGM 2006, 18(4) 334-338). Interstitial Cells of Cajal (ICC) disruption results in abnormalities in slow-wave initiation and conduction in gastroparesis (Gp), but other cell types may be important in response to GES. We hypothesized energy delivered relative to the number of cells on full thickness biopsy (FTB) is related to symptom outcome. Patients: 38 patients [12 male, 26 female, mean age 43.9 years, 31 Caucasian, Dx: 19 diabetic (DM), 19 idiopathic (ID)] were studied at baseline, and after temporary GES (tGES) placement for symptoms of Gp as described (GIE 74: 496-503). Methods: Patients were studied at baseline, after tGES placement with standardized symptom scores (Sx) using a patient reported outcome (PRO) diary and solid/liquid gastric emptying time. Energy parameters were calculated as charge/ pulse, energy/pulse, power/pulse and average power using electrical engineering formulas. FTBs were obtained at subsequent permanent GES implantation and analyzed for CD117/ Cajal, S100 and Mast cells per high-power field (hpf). We compared energy parameters and cells (product of energy parameters and cell density) from FTBs to results of Gp Sx after tGES by Wilcoxon 2 sample tests and Spearman correlations reported as mean (SD). Results: Table 1 shows number of cells by energy metric and diabetic status. Number of cells/hpf for inner (p=0.02) and outer layers (p<0.001) of mast cells for DM vs ID were significantly different. Charge of outer layer of mast cells in DM vs ID was significantly different (p<0.001). In outer layer of mast cells, energy, power and average power parameters in DM vs ID were significantly different (p=0.03). Charge in inner layer of S100 cells in DM vs ID (p<0.02) was significantly different. No significant difference in cells or energy parameters in ICC for
S-719
AGA Abstracts