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Mo1594 High Prevalence of Gastroparesis in Patients With Parkinson's Disease and Chronic Constipation Studied by Wireless Motility Capsule
Mo1594 High Prevalence of Gastroparesis in Patients With Parkinson's Disease and Chronic Constipation Studied by Wireless Motility Capsule Andrew Su, Carrolee Barlow, Rita Gandhy, George Triadafilopoulos Background: Chronic constipation is the single most common gastrointestinal symptom in Parkinson's Disease (PD), and is reported in up to 80-90% of patients. The wireless motility capsule (WMC) system is a simple and minimally invasive procedure that can be performed in the ambulatory setting. It is a validated test that can be used to quantify colonic transit times in chronic constipation, but will also measure gastric, small intestine, and whole gut transit times as well. Aims: To assess the prevalence and severity of gastric and small intestinal transit delay in PD patients with constipation undergoing evaluation with WMC. Methods: Retrospective chart review of all patients with PD referred to a Neurogastroenterology and Motility Center for assessment and treatment of chronic constipation. All patients in the cohort had thorough clinical evaluation followed by ancillary testing with WMC using standard protocol and with patients off laxatives but maintained on their PD medications. Results: We studied 30 (24M: 6F, mean age 72, range 58-89) patients with PD and chronic constipation. Four WMC studies were technically inadequate and were excluded. Of the 26 studies analyzed, 16 (62%) revealed an abnormally prolonged gastric emptying time (normal < 240 min), 3 (11%) prolonged small bowel transit time (normal < 360 min), 18 (69%) prolonged colonic transit time (normal < 3540 min), and 20 (77%) prolonged whole gut transit time (normal < 4380 min). Among those with abnormal gastric emptying times the mean was 470 ± 39 min, almost twice the upper limit of normal. Small bowel transit appears to be preserved in most patients with PD. Not surprisingly, colonic transit times and whole gut transit times were prolonged in most patients. The mean colonic transit time among those who had delayed colonic transit was 4730 ± 77 min. Conclusions: The disturbingly high prevalence and magnitude of gastroparesis seen in this cohort may contribute not only to symptoms (bloating, weight loss) but also to altered pharmacodynamics of PD medications resulting in poor drug efficacy. WMC is a valuable clinical tool in the assessment of PD patients since it may highlight unsuspected abnormalities amenable to therapeutic intervention.
Bar graph depicting the most commonly reported adverse events after GES implantation. Findings are grouped as 'localized problems' (black bars), 'system failure' (white bars), 'patient complaints' (dark grey bars), or lack/loss of benefit (light grey bars).
Mo1595 Long-Term Cardiac Safety of Very High-Dose Domperidone for the Treatment of Gastroparesis: A Single Center Experience Marco A. Bustamante Bernal, Jose L. Gonzalez Martinez, Alejandro Barreda, Yvette Gomez, Richard W. McCallum Introduction: Domperidone is a prokinetic and anti-emetic by blocking dopamine 2 (D2) receptors in the gut and also centrally in the chemoreceptor trigger zone respectively. It has been approved throughout the world since 1974 for the treatment of gastroparesis, nausea and vomiting. However, in the United States it is only available through an FDA-approved Limited Access Program. There has been increasing focus on the concern that domperidone has potential cardiac toxicity, specifically QTc interval prolongation that could potentially lead to fatal arrhythmias. Objective: Report a single center experience with very high doses of domperidone (80-120 mg/day) - 2 to 3 fold greater than standard dosing- for the treatment of gastroparesis while monitoring for cardiac toxicity. Methods: A retrospective chart review was conducted of patients with diagnosis of gastroparesis from January 2013 and November 2015 who were receiving domperidone under an Investigational New Drug (IND) protocol. Patient demographics, indications for therapy, domperidone dose, and concomitant use of drugs that could potentially prolong the QTc interval were all reviewed. An electrocardiogram (EKG) was obtained at enrollment and subsequent office visits. Prolonged QTc interval was defined if >450 ms in males and >470 ms in females. Results: A total of 37 patients, 31 female (27% Hispanic, 73% White), were taking domperidone for gastroparesis (idiopathic 64.9%, diabetic 29.7%, post-surgical 5.4%). Domperidone dosage in 11 patients ranged from 40-80 mg/day; from 80-120 mg/day in 26 (70.3%) and 22 patients (59.4%) were taking at least one other medication that could potentially prolong the QTc interval (ondansetron: 13, beta-blocker: 5, tricyclic antidepressants: 7, fluoroquinolones 3, dabigatran 1). The median QTc interval obtained at enrollment in 37 patients was 419.9 ms (range: 351468ms). Median clinical follow-up was 8.4 months (range: 1-25 months) and EKG's obtained at intervals during this period showed a mean QTc interval of 431.8 ms (383-482 ms), not significantly different from enrollment (p= 0.10). A total of 4 patients (10.8%) were asked to stop domperidone due to concerns for cardiac safety implications; 3 with a prolonged QTc interval but no symptoms (1 patient receiving concomitant ondansetron and amitryptiline) and 1 other had palpitations and chest pain but no QTc interval prolongation. Conclusions: Our data indicate that the long-term use of very high dose domperidone, two to three times greater than the standard dosage, is safe. QTc interval prolongation without cardiovascular symptoms occurred in 8% of the patients, and there was no serious arrhythmias or fatal events observed.
Correlation between the number of reported side effects and time since GES implantation. Data are plotted for all adverse effects (white circles), adverse effects not prompting operative intervention (black circles) and those leading to corrective surgery (black squares).
Mo1593 A Miniature Wireless Gastric Stimulator for High-Energy Stimulation Rui Wang, Niranchan Paskaranandavadivel, Shameer Sathar, Peng Du, Timothy R. Angeli, Gregory O'Grady, Mehdi Kiani, Leo K. Cheng, Aydin Farajidavar Introduction: Gastric electrical stimulation (GES) with different pulse characteristics has been used as a therapy for gastrointestinal disorders. Gastric pacing has also shown potential to improve motility or symptoms through high-energy low-frequency pulses. Current gastric stimulators suffer from one or several shortcomings: bulkiness, limited stimulation combinations, and being incapable of producing high-energy pulses. We have designed, developed, and validated (bench-top and in-vivo) a wireless miniaturized system for delivering highenergy electrical stimulation to the stomach. Methods: The system is composed of a frontend module (stimulator) and a back-end module that is connected to a computer. The frontend consists of a DC-DC converter (DDC), a voltage controlled current source (VCCS), a 433MHz chip antenna, an RF matching circuit with balun, and a system-on-chip that includes a microcontroller (MC), and a transceiver. A graphical user interface was designed in LabVIEW that wirelessly transmits the stimulation parameter from the user to the front end. The MC generated a 3.7V pulse that passed through the DDC to the VCCS, which produced current pulses. The system was validated on bench-top and in-vivo in pigs. In-vivo experiments: Following mid-line laparotomy, an electrode array was placed on the mid-corpus to record slow wave activity, and the wireless stimulator was connected to pacing leads, which were inserted into the gastric wall adjacent to the proximal edge of the array, Wireless stimulation was applied on average for 150s at each pulse width (PW): 0ms (control), 500 ms, 900 ms, 500 ms, 0 ms (control). A wired data acquisition system was used to record slow waves during the period of stimulation. Results: The front-end is 11×41×3 mm, and capable of generating high-energy pulses at 10mA, with tunable PWs (100-1600ms). In the first benchtop trials, the stimulator was connected to a 500 Vresistor approximating tissue, and delivered precise monophasic pulses at various PWs. In the second trials, the stimulator leads were systematically placed apart at different distances in a saline solution, and the voltage change was measured during stimulation. The voltages over the stimulator leads were 2.1V, 2.2V, 2.3V, and 3.4V at 1, 2, 3, and 4 inches apart, demonstrating the capability of the stimulator.
Mo1596 Value of Temporal Gastric Electric Stimulators to Predict Response in Pediatric Patients With Refractory Gastroparesis Brandon Arnold, Reinaldo Garcia, Sirvart Kassabian, Matthew Wyneski, Todd Ponsky Introduction: Gastroparesis is a problem that affects pediatric patients (4.6 per 10,000). Unfortunately conventional treatment is not always successful. Gastric electrical stimulators (GES) are emerging as a possible alternative in patients that failed conventional treatment, but with the inconvenience that requires invasive surgery for the permanent placement.
S-723
AGA Abstracts
AGA Abstracts
In-vivo experiment: responses demonstrated successful tissue delivery of high-energy electrical pulses, capable of modulating slow wave initiation, pattern and frequency. Conclusion: A novel miniature wireless GES system that can deliver high-energy pulses has been developed and validated in bench-top and in-vivo experiments. The device can now be applied in experimental and clinical trials, combined with wireless recording devices, to realize a fullyfunctional closed-loop system.
Bar graph depicting the most commonly reported adverse events after GES implantation. Findings are grouped as 'localized problems' (black bars), 'system failure' (white bars), 'patient complaints' (dark grey bars), or lack/loss of benefit (light grey bars).
Mo1595 Long-Term Cardiac Safety of Very High-Dose Domperidone for the Treatment of Gastroparesis: A Single Center Experience Marco A. Bustamante Bernal, Jose L. Gonzalez Martinez, Alejandro Barreda, Yvette Gomez, Richard W. McCallum Introduction: Domperidone is a prokinetic and anti-emetic by blocking dopamine 2 (D2) receptors in the gut and also centrally in the chemoreceptor trigger zone respectively. It has been approved throughout the world since 1974 for the treatment of gastroparesis, nausea and vomiting. However, in the United States it is only available through an FDA-approved Limited Access Program. There has been increasing focus on the concern that domperidone has potential cardiac toxicity, specifically QTc interval prolongation that could potentially lead to fatal arrhythmias. Objective: Report a single center experience with very high doses of domperidone (80-120 mg/day) - 2 to 3 fold greater than standard dosing- for the treatment of gastroparesis while monitoring for cardiac toxicity. Methods: A retrospective chart review was conducted of patients with diagnosis of gastroparesis from January 2013 and November 2015 who were receiving domperidone under an Investigational New Drug (IND) protocol. Patient demographics, indications for therapy, domperidone dose, and concomitant use of drugs that could potentially prolong the QTc interval were all reviewed. An electrocardiogram (EKG) was obtained at enrollment and subsequent office visits. Prolonged QTc interval was defined if >450 ms in males and >470 ms in females. Results: A total of 37 patients, 31 female (27% Hispanic, 73% White), were taking domperidone for gastroparesis (idiopathic 64.9%, diabetic 29.7%, post-surgical 5.4%). Domperidone dosage in 11 patients ranged from 40-80 mg/day; from 80-120 mg/day in 26 (70.3%) and 22 patients (59.4%) were taking at least one other medication that could potentially prolong the QTc interval (ondansetron: 13, beta-blocker: 5, tricyclic antidepressants: 7, fluoroquinolones 3, dabigatran 1). The median QTc interval obtained at enrollment in 37 patients was 419.9 ms (range: 351468ms). Median clinical follow-up was 8.4 months (range: 1-25 months) and EKG's obtained at intervals during this period showed a mean QTc interval of 431.8 ms (383-482 ms), not significantly different from enrollment (p= 0.10). A total of 4 patients (10.8%) were asked to stop domperidone due to concerns for cardiac safety implications; 3 with a prolonged QTc interval but no symptoms (1 patient receiving concomitant ondansetron and amitryptiline) and 1 other had palpitations and chest pain but no QTc interval prolongation. Conclusions: Our data indicate that the long-term use of very high dose domperidone, two to three times greater than the standard dosage, is safe. QTc interval prolongation without cardiovascular symptoms occurred in 8% of the patients, and there was no serious arrhythmias or fatal events observed.
Correlation between the number of reported side effects and time since GES implantation. Data are plotted for all adverse effects (white circles), adverse effects not prompting operative intervention (black circles) and those leading to corrective surgery (black squares).
Mo1593 A Miniature Wireless Gastric Stimulator for High-Energy Stimulation Rui Wang, Niranchan Paskaranandavadivel, Shameer Sathar, Peng Du, Timothy R. Angeli, Gregory O'Grady, Mehdi Kiani, Leo K. Cheng, Aydin Farajidavar Introduction: Gastric electrical stimulation (GES) with different pulse characteristics has been used as a therapy for gastrointestinal disorders. Gastric pacing has also shown potential to improve motility or symptoms through high-energy low-frequency pulses. Current gastric stimulators suffer from one or several shortcomings: bulkiness, limited stimulation combinations, and being incapable of producing high-energy pulses. We have designed, developed, and validated (bench-top and in-vivo) a wireless miniaturized system for delivering highenergy electrical stimulation to the stomach. Methods: The system is composed of a frontend module (stimulator) and a back-end module that is connected to a computer. The frontend consists of a DC-DC converter (DDC), a voltage controlled current source (VCCS), a 433MHz chip antenna, an RF matching circuit with balun, and a system-on-chip that includes a microcontroller (MC), and a transceiver. A graphical user interface was designed in LabVIEW that wirelessly transmits the stimulation parameter from the user to the front end. The MC generated a 3.7V pulse that passed through the DDC to the VCCS, which produced current pulses. The system was validated on bench-top and in-vivo in pigs. In-vivo experiments: Following mid-line laparotomy, an electrode array was placed on the mid-corpus to record slow wave activity, and the wireless stimulator was connected to pacing leads, which were inserted into the gastric wall adjacent to the proximal edge of the array, Wireless stimulation was applied on average for 150s at each pulse width (PW): 0ms (control), 500 ms, 900 ms, 500 ms, 0 ms (control). A wired data acquisition system was used to record slow waves during the period of stimulation. Results: The front-end is 11×41×3 mm, and capable of generating high-energy pulses at 10mA, with tunable PWs (100-1600ms). In the first benchtop trials, the stimulator was connected to a 500 Vresistor approximating tissue, and delivered precise monophasic pulses at various PWs. In the second trials, the stimulator leads were systematically placed apart at different distances in a saline solution, and the voltage change was measured during stimulation. The voltages over the stimulator leads were 2.1V, 2.2V, 2.3V, and 3.4V at 1, 2, 3, and 4 inches apart, demonstrating the capability of the stimulator.
Mo1596 Value of Temporal Gastric Electric Stimulators to Predict Response in Pediatric Patients With Refractory Gastroparesis Brandon Arnold, Reinaldo Garcia, Sirvart Kassabian, Matthew Wyneski, Todd Ponsky Introduction: Gastroparesis is a problem that affects pediatric patients (4.6 per 10,000). Unfortunately conventional treatment is not always successful. Gastric electrical stimulators (GES) are emerging as a possible alternative in patients that failed conventional treatment, but with the inconvenience that requires invasive surgery for the permanent placement.
S-723
AGA Abstracts
AGA Abstracts
In-vivo experiment: responses demonstrated successful tissue delivery of high-energy electrical pulses, capable of modulating slow wave initiation, pattern and frequency. Conclusion: A novel miniature wireless GES system that can deliver high-energy pulses has been developed and validated in bench-top and in-vivo experiments. The device can now be applied in experimental and clinical trials, combined with wireless recording devices, to realize a fullyfunctional closed-loop system.