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Mo1608 Simultaneous EGG and Wireless Motility Capsule Recording in Gastroparesis: Abnormal Slow-Wave Direction Associated With Increased Gastric Pressure
with gastroparesis [1]. High-resolution electrical mapping has recently been used to understand the details of stomach slow-wave activity [2,3]. This technique involves positioning a spatially dense electrode array directly on the stomach surface to allow for the reconstruction of the patterns of spatiotemporal electrical activation. These recordings revealed that abnormal slow-wave patterns occurred at the normal 3 cpm frequency in half of the gastroparesis patients. Since a single-channel EGG measurement lacks spatial resolution, it fundamentally cannot detect these types of abnormalities [4]. Methods and Results: High-resolution EGG was carried out on five normal subjects as well as a subject with idiopathic gastroparesis using a newly developed approach for detecting slow-wave propagation with an array of cutaneous electrodes. The recording was time-synchronized to a wireless motility capsule, which measured internal pressure and pH. Although the gastroparetic subject exhibited normal 3 cpm EGG activity throughout the 5 hour recording, we were able to detect episodes of abnormal slow wave propagation. Interestingly, these episodes of abnormal propagation coincided with periods of higher pressure (> 10 mmHg) as measured by the motility capsule (Figure 1). EGG slow-wave frequency was 3 cpm and spatial direction was quite uniform among the normal subjects (Figure 2). Conclusion: These results show that slow-wave spatial abnormalities can be detected non-invasively using an electrode array. Further testing is necessary to establish the diagnostic ability of this approach and the effectiveness of different therapies on normalization of the slow-wave. In addition, more study is needed to understand the relationship between the slow-wave spatial abnormalities and gastric contractility. References: [1] R. J. Brzana, et al., The American Journal of Gastroenterology , 93.10 (1998): 1803-1809. [2] G. O'Grady, et al., American Journal of Physiology-Gastrointestinal and Liver Physiology, 299.3 (2010): G585-G592. [3] G. O'Grady, et al., Gastroenterology, 143.3 (2012): 589-598. [4] M. L. Buist, et al., Experimental Physiology, 91.2 (2006): 383-390.
AGA Abstracts
Table 1. Taste, Smell, GCSI, and HB/RG Scores in the Four Study Groups
Table 2. Correlation of Taste and Smell Scores with GSCI and HB/RG Scores
Figure 1: Polar histogram of the slow-wave direction throughout recording for subject with idiopathic gastroparesis. Abnormal wave direction associated with pressure greater than 3mmHg.
Mo1607 Supratherapeutic Dose of Metoclopramide Nasal Spray Shown to Have No ECG Effects in Healthy Male and Female Volunteers: Results of the First Metoclopramide Thorough ECG Study Marilyn R. Carlson, Wayne Alves, Jay W. Mason Metoclopramide, the only FDA-approved drug for gastroparesis, is widely used by patients with multiple medical conditions, such as diabetes, that put them at increased risk for cardiac events. Since metoclopramide tablets and injection were approved in 1980, there have been very few reports of torsades de pointes, cardiac arrest, and/or sudden death associated with the use of the FDA-approved doses of the oral formulation. Literature reports of cardiac events are primarily associated with parenteral administration in patients who are medically compromised, but there has been a lack of information for prescribing physicians regarding the effects of metoclopramide on the QT interval. Evoke Pharma is developing a nasal spray formulation of metoclopramide for patients with diabetic gastroparesis and performed the first metoclopramide thorough electrocardiogram (ECG) study. Aims: The primary objective of the study was to define the ECG effects of an 80 mg supratherapeutic dose of metoclopramide nasal spray administered to healthy adult male and female subjects. The secondary objectives were to define the ECG effects of a 20 mg metoclopramide nasal spray dose, and to assess assay sensitivity with an active control, moxifloxacin. In addition, the safety and pharmacokinetics of both doses of metoclopramide nasal spray were evaluated. Methods: The study was conducted using a double-blind, double-dummy, randomized, four-period crossover design. Subjects were randomized to receive placebo nasal spray, 20 mg metoclopramide nasal spray, 80 mg metoclopramide nasal spray, and 400 mg of oral moxifloxacin under fasting conditions in a random sequence separated by a minimum fourday washout period between doses. Safety was evaluated by adverse events, clinical laboratory test results, vital sign measurements, 12-lead safety ECG results, and physical and nasal examination findings. Results: Metoclopramide nasal spray did not increase the corrected QT interval at the therapeutic and supratherapeutic doses tested while the expected extent and pattern of change during moxifloxacin treatment was observed. Heart rate and PR interval increased modestly in the moxifloxacin arm, but there were no consistent or clinically significant changes associated with any of the treatments. Mean metoclopramide plasma PK exposure parameters (Cmax and AUC0-t) were approximately dose proportional across the 20 to 80 mg dose range of the nasal spray. There were no SAEs, no drops due to AE, and all 48 subjects completed the study. Conclusions: These negative ECG results for metoclopramide nasal spray at 80 mg (8 times the clinical dose) provide useful clinical information for prescribing physicians and their patients with acute or recurrent symptoms of diabetic gastroparesis who will most often be dosed with 10 mg of metoclopramide nasal spray before meals and at bedtime for 28 days.
Figure 2: Polar histogram of the slow-wave direction throughout recording for a normal subject.
Mo1609 The Overlooked Factors That May Lead to Delayed Gastric Emptying Mubarak W. Sayyar, Lini Edwin, Jigar Patel, Anand Nath, Eshetu Tefera, Won Cho Introduction Gastroparesis is a gastrointestinal disorder presenting as chronic nausea, vomiting and abdominal pain. Although electrolyte imbalances are believed to affect gastric motility, current literature has very limited data on how electrolyte changes may affect gastric motility. Our aim is to conduct a retrospective study to evaluate the effect of various factors on gastric motility by assessing their effects on gastric emptying study (GES) results. Method A retrospective review of the Nuclear Medicine database was performed for patients who had GES in MedStar Washington Hospital Center from January 2011 to May 2014. Patients were deemed eligible for the study if GES was performed and serum hemoglobin A1C drawn within 3 months, or comprehensive metabolic panel was collected within a week, or thyroid function test was collected within 6 weeks of the index study. Patients were excluded if they had structural pathology on EGD, colonoscopy or pathology reports; comorbidities such as cirrhosis, neurological disease, scleroderma, HIV; previous abdominal surgery, constipation, or prokinetic medication at the time of study. Abnormalities in gastric emptying
Mo1608 Simultaneous EGG and Wireless Motility Capsule Recording in Gastroparesis: Abnormal Slow-Wave Direction Associated With Increased Gastric Pressure Armen A. Gharibans, David C. Kunkel, Sanggyun Kim, Todd P. Coleman Background: Electrogastrography (EGG) is a noninvasive technique for recording gastric myoelectrical activity using electrodes placed cutaneously on the abdominal surface overlaying the stomach. Abnormalities in EGG frequency and power have been observed in patients
AGA Abstracts
S-728
AGA Abstracts
Table 1. Taste, Smell, GCSI, and HB/RG Scores in the Four Study Groups
Table 2. Correlation of Taste and Smell Scores with GSCI and HB/RG Scores
Figure 1: Polar histogram of the slow-wave direction throughout recording for subject with idiopathic gastroparesis. Abnormal wave direction associated with pressure greater than 3mmHg.
Mo1607 Supratherapeutic Dose of Metoclopramide Nasal Spray Shown to Have No ECG Effects in Healthy Male and Female Volunteers: Results of the First Metoclopramide Thorough ECG Study Marilyn R. Carlson, Wayne Alves, Jay W. Mason Metoclopramide, the only FDA-approved drug for gastroparesis, is widely used by patients with multiple medical conditions, such as diabetes, that put them at increased risk for cardiac events. Since metoclopramide tablets and injection were approved in 1980, there have been very few reports of torsades de pointes, cardiac arrest, and/or sudden death associated with the use of the FDA-approved doses of the oral formulation. Literature reports of cardiac events are primarily associated with parenteral administration in patients who are medically compromised, but there has been a lack of information for prescribing physicians regarding the effects of metoclopramide on the QT interval. Evoke Pharma is developing a nasal spray formulation of metoclopramide for patients with diabetic gastroparesis and performed the first metoclopramide thorough electrocardiogram (ECG) study. Aims: The primary objective of the study was to define the ECG effects of an 80 mg supratherapeutic dose of metoclopramide nasal spray administered to healthy adult male and female subjects. The secondary objectives were to define the ECG effects of a 20 mg metoclopramide nasal spray dose, and to assess assay sensitivity with an active control, moxifloxacin. In addition, the safety and pharmacokinetics of both doses of metoclopramide nasal spray were evaluated. Methods: The study was conducted using a double-blind, double-dummy, randomized, four-period crossover design. Subjects were randomized to receive placebo nasal spray, 20 mg metoclopramide nasal spray, 80 mg metoclopramide nasal spray, and 400 mg of oral moxifloxacin under fasting conditions in a random sequence separated by a minimum fourday washout period between doses. Safety was evaluated by adverse events, clinical laboratory test results, vital sign measurements, 12-lead safety ECG results, and physical and nasal examination findings. Results: Metoclopramide nasal spray did not increase the corrected QT interval at the therapeutic and supratherapeutic doses tested while the expected extent and pattern of change during moxifloxacin treatment was observed. Heart rate and PR interval increased modestly in the moxifloxacin arm, but there were no consistent or clinically significant changes associated with any of the treatments. Mean metoclopramide plasma PK exposure parameters (Cmax and AUC0-t) were approximately dose proportional across the 20 to 80 mg dose range of the nasal spray. There were no SAEs, no drops due to AE, and all 48 subjects completed the study. Conclusions: These negative ECG results for metoclopramide nasal spray at 80 mg (8 times the clinical dose) provide useful clinical information for prescribing physicians and their patients with acute or recurrent symptoms of diabetic gastroparesis who will most often be dosed with 10 mg of metoclopramide nasal spray before meals and at bedtime for 28 days.
Figure 2: Polar histogram of the slow-wave direction throughout recording for a normal subject.
Mo1609 The Overlooked Factors That May Lead to Delayed Gastric Emptying Mubarak W. Sayyar, Lini Edwin, Jigar Patel, Anand Nath, Eshetu Tefera, Won Cho Introduction Gastroparesis is a gastrointestinal disorder presenting as chronic nausea, vomiting and abdominal pain. Although electrolyte imbalances are believed to affect gastric motility, current literature has very limited data on how electrolyte changes may affect gastric motility. Our aim is to conduct a retrospective study to evaluate the effect of various factors on gastric motility by assessing their effects on gastric emptying study (GES) results. Method A retrospective review of the Nuclear Medicine database was performed for patients who had GES in MedStar Washington Hospital Center from January 2011 to May 2014. Patients were deemed eligible for the study if GES was performed and serum hemoglobin A1C drawn within 3 months, or comprehensive metabolic panel was collected within a week, or thyroid function test was collected within 6 weeks of the index study. Patients were excluded if they had structural pathology on EGD, colonoscopy or pathology reports; comorbidities such as cirrhosis, neurological disease, scleroderma, HIV; previous abdominal surgery, constipation, or prokinetic medication at the time of study. Abnormalities in gastric emptying
Mo1608 Simultaneous EGG and Wireless Motility Capsule Recording in Gastroparesis: Abnormal Slow-Wave Direction Associated With Increased Gastric Pressure Armen A. Gharibans, David C. Kunkel, Sanggyun Kim, Todd P. Coleman Background: Electrogastrography (EGG) is a noninvasive technique for recording gastric myoelectrical activity using electrodes placed cutaneously on the abdominal surface overlaying the stomach. Abnormalities in EGG frequency and power have been observed in patients
AGA Abstracts
S-728