Benefits of Prokinetics, Gastroparesis Diet, or Neuromodulators Alone or in Combination for Symptoms of Gastroparesis.

BACKGROUND & AIMS: Prokinetics have limited effectiveness for treating symptoms of gastroparesis. Thus, alternative or adjunct therapies, such as gastroparesis diets or neuromodulators, are often prescribed. Their therapeutic benefits alone or in combination remain unclear. METHODS: One hundred and twenty-nine patients with symptoms of gastroparesis underwent wireless motility capsule gastric emptying time and gastric emptying scintigraphy. Based on test results, changes in therapy were recommended. Changes in Gastroparesis Cardinal Symptom Index (GCSI) and individual symptom scores over 6 months were related to recommendations for prokinetics, gastroparesis diet, or neuromodulators given as solo new therapies or in dual combinations. Multivariate analyses were performed to adjust for gastric emptying and other variables. RESULTS: In the whole group regardless of therapy, GCSI scores decreased by 0.53 points (interquartile range, -1.25 to 0.05; P < .0001) over 6 months. GCSI did not decrease for prokinetics as solo new therapy (P = .95). Conversely, neuromodulators as solo therapy decreased GCSI scores (P = .04) and all individual symptoms except nausea/vomiting (P = .86). Prokinetics combined with gastroparesis diets or neuromodulators improved GCSI scores (P ≤ .04) and most individual symptoms. Adjusting for gastric emptying time on multivariate analyses showed greater GCSI decreases for nondelayed emptying for neuromodulators as solo new therapy (P = .01). Gastric emptying scintigraphy, gender, diabetes, and functional dyspepsia did not influence responses to any treatment. CONCLUSIONS: Initiating prokinetics as solo new therapy had little benefit for patients with symptoms of gastroparesis. Neuromodulators as the only new therapy decreased symptoms other than nausea and vomiting, especially with nondelayed gastric emptying. Adding gastroparesis diets or neuromodulators to prokinetics offered relief, suggesting that combination therapies may be more useful in managing these patients. (ClinicalTrials.gov NCT02022826.).

Gastric Alimetry Expands Patient Phenotyping in Gastroduodenal Disorders Compared with Gastric Emptying Scintigraphy.

INTRODUCTION: Gastric emptying testing (GET) assesses gastric motility, however, is nonspecific and insensitive for neuromuscular disorders. Gastric Alimetry (GA) is a new medical device combining noninvasive gastric electrophysiological mapping and validated symptom profiling. This study assessed patient-specific phenotyping using GA compared with GET. METHODS: Patients with chronic gastroduodenal symptoms underwent simultaneous GET and GA, comprising a 30-minute baseline, 99m TC-labelled egg meal, and 4-hour postprandial recording. Results were referenced to normative ranges. Symptoms were profiled in the validated GA App and phenotyped using rule-based criteria based on their relationships to the meal and gastric activity: (i) sensorimotor, (ii) continuous, and (iii) other. RESULTS: Seventy-five patients were assessed, 77% female. Motility abnormality detection rates were as follows: GET 22.7% (14 delayed, 3 rapid), GA spectral analysis 33.3% (14 low rhythm stability/low amplitude, 5 high amplitude, and 6 abnormal frequency), and combined yield 42.7%. In patients with normal spectral analysis, GA symptom phenotypes included sensorimotor 17% (where symptoms strongly paired with gastric amplitude, median r = 0.61), continuous 30%, and other 53%. GA phenotypes showed superior correlations with Gastroparesis Cardinal Symptom Index, Patient Assessment of Upper Gastrointestinal Symptom Severity Index, and anxiety scales, whereas Rome IV Criteria did not correlate with psychometric scores ( P > 0.05). Delayed emptying was not predictive of specific GA phenotypes. DISCUSSION: GA improves patient phenotyping in chronic gastroduodenal disorders in the presence and absence of motility abnormalities with increased correlation with symptoms and psychometrics compared with gastric emptying status and Rome IV criteria. These findings have implications for the diagnostic profiling and personalized management of gastroduodenal disorders.

Whole Gut Transit Scintigraphy for the Assessment of Patients with Symptoms of Chronic Constipation.

INTRODUCTION: Whole gut transit scintigraphy (WGTS) can detect delayed colonic transit (CT), different types of CT delays, and assess upper GI tract transit. AIM: To delineate the frequency of different types of CT patterns in patients with chronic constipation (CC), determine the relationship between these CT patterns and upper GI tract transit abnormalities, and assess how symptoms relate to different colonic transit patterns. METHODS: Retrospective review of patients who had WGTS for CC. Patients completed a modified PAGI-SYM questionnaire to assess symptoms. Patients ingested a standard solid (Tc-99m egg sandwich)-liquid (In-111 water) meal to assess solid meal gastric emptying (GE), liquid GE, small bowel transit (SBT), and geometric center of colonic activity at 24, 48, and 72h. RESULTS: One hundred and eighty six patients underwent WGTS. Main symptoms were constipation (41%), nausea (24%), and bloating (22%). CT assessment showed 32% of patients had normal transit, 31% colonic inertia (CI), 28% functional rectosigmoid obstruction (FRS0), and 9% generalized slow colonic transit (GSCT). GE was delayed in 36%; more commonly in CI and FRSO. SBT was delayed in 19%; more commonly in GSCT and CI. Patients with CI had less bowel movements per week whereas patients with normal CT had more bm/week. CONCLUSIONS: In this series of patients with symptomatic constipation, WGTS assessment showed delayed colonic transit in 68% of patients, with 31% having colonic inertia, 28% a functional rectosigmoid obstruction pattern, and 9% generalized delay in colonic transit. Abnormalities in GE and SBT were present in 36 and 19%. WGTS is helpful to document delayed colonic transit (CT), assess the pattern of the delay in CT, and determine if there are upper GI transit abnormalities.

Low Vitamin D Levels in Patients with Symptoms of Gastroparesis: Relationships with Nausea and Vomiting, Gastric Emptying and Gastric Myoelectrical Activity.

Patients with gastroparesis (Gp) often have diets deficient in calories, electrolytes, and vitamins. Vitamin D levels have been reported to be low in some patients with Gp but has not been systematically studied. AIMS: To determine vitamin D levels and relationships among symptoms, gastric emptying and gastric myoelectrical activity (GMA) in patients with symptoms of Gp. METHODS: 25-hydroxy-vitamin D was measured in patients at enrollment in the Gastroparesis Clinical Consortium Registry. Gastroparesis Cardinal Symptoms Index (GCSI), gastric emptying, and GMA before and after water load satiety test (WLST) were measured. GMA, expressed as percentage distribution of activity in normal and dysrhythmic ranges, was recorded using electrogastrography. RESULTS: Overall, vitamin D levels were low (< 30 ng/ml) in 288 of 513 (56.1%) patients with symptoms of Gp (206 of 376 (54.8%) patients with delayed gastric emptying (Gp) and 82 of 137 (59.9%) patients with symptoms of Gp and normal gastric emptying). Low vitamin D levels were associated with increased nausea and vomiting (P < 0.0001), but not with fullness or bloating subscores. Low vitamin D levels in patients with Gp were associated with greater meal retention at four hours (36% retention) compared with Gp patients with normal vitamin D levels (31% retention; P = 0.05). Low vitamin D in patients with normal gastric emptying was associated with decreased normal 3 cpm GMA before (P = 0.001) and increased tachygastria after WLST (P = 0.01). CONCLUSIONS: Low vitamin D levels are present in half the patients with symptoms of gastroparesis and are associated with nausea and vomiting and gastric neuromuscular dysfunction.

Relationships among intragastric meal distribution during gastric emptying scintigraphy, water consumption during water load satiety testing, and symptoms of gastroparesis.

Gastric emptying scintigraphy (GES) measures total gastric retention after a solid meal and can assess intragastric meal distribution (IMD). Water load satiety test (WLST) measures gastric capacity. Both IMD immediately after meal ingestion [ratio of proximal gastric counts after meal ingestion to total gastric counts at time 0 (IMD0)] and WLST (volume of water ingested over 5 min) are indirect measures of gastric accommodation. In this study, IMD0 and WLST were compared with each other and to symptoms of gastroparesis to gauge their clinical utility for assessing patients with symptoms of gastroparesis. Patients with symptoms of gastroparesis underwent GES to obtain gastric retention and IMD0, WLST, and filled out patient assessment of upper GI symptoms. A total of 234 patients with symptoms of gastroparesis were assessed (86 patients with diabetes, 130 idiopathic, 18 postfundoplication) and 175 (75%) delayed gastric emptying. Low IMD0 <0.568 suggesting initial rapid transit to the distal stomach was present in 8% and correlated with lower gastric retention, less heartburn, and lower volumes consumed during WLST. Low WLST volume (<238 mL) was present in 20% and associated with increased severity of early satiety, postprandial fullness, loss of appetite, and nausea. Low IMD0 is associated with less gastric retention and less heartburn. Volume of water consumed during WLST, while associated with IMD0, has associations with early satiety, postprandial fullness, loss of appetite, and nausea. Thus, IMD0 and WLST appear to overlap somewhat in their assessment of gastric physiology in adults with symptoms of gastroparesis but relate to different dyspeptic symptoms.NEW & NOTEWORTHY IMD0 and WLST were assessed for their clinical utility in assessing patients with symptoms of gastroparesis. Low IMD0 is associated with less gastric retention and less heartburn. Volume of water consumed during WLST, while associated with IMD0, has associations with early satiety, postprandial fullness, loss of appetite, and nausea. IMD0 and WLST appear to overlap somewhat in their assessment of gastric physiology in adults with symptoms of gastroparesis but relate to different dyspeptic symptoms.

Metoclopramide Nasal Spray in Women with Symptomatic Diabetic Gastroparesis: A Randomized, Double-Blind, Placebo-Controlled Phase 3 Study.

BACKGROUND & AIMS: Metoclopramide nasal spray (MNS) was developed as an alternative to oral metoclopramide. Prior phase 2 studies demonstrated efficacy in reducing symptoms in women, but not men with diabetic gastroparesis. The aim of this phase 3 study was to further determine the safety and efficacy of MNS compared with placebo in reducing symptoms of diabetic gastroparesis in women. METHODS: This US multicenter, randomized, double-blind, parallel group study enrolled women aged 18-75 years with diabetic gastroparesis and delayed gastric emptying. Subjects were randomized 1:1 to receive placebo or MNS 10 mg. The primary efficacy end point was change in mean daily Gastroparesis Symptom Assessment total score from baseline to Week 4. The Gastroparesis Symptom Assessment daily diary is a validated patient-reported outcome instrument that averages scores of nausea, early satiety, prolonged fullness, bloating, and upper abdominal pain on a 5-point ordinal scale. RESULTS: Two hundred and five subjects were randomized to receive placebo (n = 103) or MNS (n = 102). Overall, the MNS group did not experience a significant reduction in symptoms compared with the placebo group from baseline to Week 4 (P = .881). However, subjects with moderate-to-severe symptoms at baseline had a significant treatment effect from Weeks 1 to 3 (P < .05) and experienced a significant reduction in nausea and upper abdominal pain for all 4 weeks versus placebo (P < .05). Treatment-emergent adverse events were primarily mild to moderate with headache and abdominal pain reported most frequently. CONCLUSIONS: Although the primary end point was not met using all enrolled patients, treatment with MNS provided significant relief for women with moderate-to-severe diabetic gastroparesis symptoms. MNS was well tolerated and demonstrated a similar safety profile to placebo. (ClinicalTrials.gov identifier: NCT02025725.).

Normative Values for Body Surface Gastric Mapping Evaluations of Gastric Motility Using Gastric Alimetry: Spectral Analysis.

INTRODUCTION: Body surface gastric mapping (BSGM) is a new noninvasive test of gastric function. BSGM offers several novel and improved biomarkers of gastric function capable of differentiating patients with overlapping symptom profiles. The aim of this study was to define normative reference intervals for BSGM spectral metrics in a population of healthy controls. METHODS: BSGM was performed in healthy controls using Gastric Alimetry (Alimetry, New Zealand) comprising a stretchable high-resolution array (8 × 8 electrodes; 196 cm 2 ), wearable Reader, and validated symptom-logging App. The evaluation encompassed a fasting baseline (30 minutes), 482 kCal meal, and 4-hour postprandial recording. Normative reference intervals were calculated for BSGM metrics including the Principal Gastric Frequency, Gastric Alimetry Rhythm Index (a measure of the concentration of power in the gastric frequency band over time), body mass index (BMI)-adjusted amplitude (µV), and fed:fasted amplitude ratio. Data were reported as median and reference interval (5th and/or 95th percentiles). RESULTS: A total of 110 subjects (55% female, median age 32 years [interquartile range 24-50], median BMI 23.8 kg/m 2 [interquartile range 21.4-26.9]) were included. The median Principal Gastric Frequency was 3.04 cycles per minute; reference interval: 2.65-3.35 cycles per minute. The median Gastric Alimetry Rhythm Index was 0.50; reference interval: ≥0.25. The median BMI-adjusted amplitude was 37.6 µV; reference interval: 20-70 µV. The median fed:fasted amplitude ratio was 1.85; reference interval ≥1.08. A higher BMI was associated with a shorter meal-response duration ( P = 0.014). DISCUSSION: This study provides normative reference intervals for BSGM spectral data to inform diagnostic interpretations of abnormal gastric function.

Dysphagia in Neurological Disorders.

Dysphagia is a common symptom in many neurologic disorders. Patients with oropharyngeal dysphagia present with difficulties when they start to swallow, often with coughing and choking; whereas patients with esophageal dysphagia describe the feeling that swallowed food stops in the chest. Chronic neurologic diseases such stroke, Parkinson's disease, or dementia often have dysphagia as a symptom, particularly oropharyngeal dysphagia, and the term "neurogenic dysphagia" is often used. A disruption of the sophisticated, integrated sensorimotor swallowing system is usually the main reason behind dysphagia. Dysphagia can be associated with aspiration leading to aspiration pneumonia, and chronic dysphagia can lead to weight loss and malnutrition. Patients with dysphagia, when accurately and promptly diagnosed through medical history, physical examination, and diagnostic tests, often can be treated and experience improved quality of life. The pathophysiological mechanisms behind dysphagia, its diagnosis, and potential treatments are discussed in this manuscript.

Atypical Causes of Gastroparesis: Prevalence, Gastric Emptying, and Clinical Features.

BACKGROUND: Gastroparesis is commonly attributed to idiopathic or diabetic causes. GOALS: We aimed to describe atypical causes of gastroparesis and examine the clinical features and severity of delayed gastric emptying compared with idiopathic and diabetic causes. STUDY: Between 2018 and 2021, gastroparesis patients being evaluated at our tertiary care center completed a 4-hour gastric emptying scintigraphy and questionnaires assessing for gastrointestinal disorders, including patient assessment of upper gastrointestinal symptoms. Patients were divided into groups relating to gastroparesis cause: diabetic, postsurgical (PSGp), connective tissue (CTGp), neurological and idiopathic. RESULTS: Two hundred fifty-six patients with delayed emptying on gastric emptying scintigraphy completed the questionnaires. Gastroparesis causes included 149 (58.2%) idiopathic, 60 (23.4%) diabetic, 29 (11.3%) postsurgical, 13 (5.1%) connective tissue, and 5 (2.0%) neurological. In each group, most patients were female and White. Gastric retention at 4 hours was significantly greater in patients with diabetic (39.3±25.7% P <0.001), postsurgical (41.3±24.0% P =0.002), and connective tissue gastroparesis (37.8±20.0% P =0.049) compared with patients with idiopathic gastroparesis (25.5±17.6%). In PSGp, diabetic and idiopathic causes, the main symptoms were early satiety and postprandial fullness, whereas in CTGp, bloating and abdominal distension were the predominant symptoms. Vomiting severity was significantly greater in patients with diabetes compared with idiopathic gastroparesis (2.9±1.9 vs. 2.1±1.8 P =0.006). CONCLUSIONS: Atypical causes contributed to gastroparesis in 47 of 256 (18.4%) patients with delayed gastric emptying. Gastric emptying was significantly more delayed in PSGp and CTGp patients. PSGp patients mainly experienced stomach fullness and early satiety, whereas CTGp patients had predominantly bloating and distension.

Trends in Gastroparesis Management: A United States Population-based Study From 2010 to 2020.

BACKGROUND: There is little consensus on the medical management of gastroparesis, a disorder characterized by delayed gastric emptying with symptoms of early satiety, nausea, vomiting, and upper abdominal pain. GOALS: We utilized population-level data to: (1) describe the prevalence of different pharmacological and nonpharmacological therapies in patients with gastroparesis; and (2) trend the prevalence of these therapies from 2010 to 2020. STUDY: More than 59 million unique medical records across 26 US-based major health care systems were surveyed using the Explorys platform to identify a cohort of adults with gastroparesis who completed both a gastric emptying study and upper endoscopy or upper gastrointestinal tract imaging. Prevalence of antiemetic, prokinetic, neuromodulator prescriptions, and surgical therapies for gastroparesis were searched within this cohort and trended annually from 2010 to 2020. RESULTS: Antiemetics (72% of patients), prokinetics (47%), and neuromodulators (75% of patients, 44% of patients without a concomitant psychiatric or diabetic peripheral neuropathy diagnosis) were all commonly used in the treatment of patients with gastroparesis. From 2010 to 2020, there was an increase in the prevalence of antiemetic and neuromodulator prescriptions (36.4% to 57.6%, P <0.001 and 47.0% to 66.9%, P <0.001, respectively), whereas the prevalence of prokinetics remained relatively constant (31.8% to 31.6%, P =0.52). Procedural and surgical treatments were used in 5% of gastroparesis patients. CONCLUSIONS: Treatments for gastroparesis have changed over the last decade: antiemetic and neuromodulator use has increased whereas prokinetic use has remained constant. This practice pattern may reflect the growing number and availability of antiemetics and neuromodulators and the small number and known side effects of prokinetics.

Hair Loss in Patients with Gastroparesis: A Sign of Nutritional Deficiency in Gastroparesis?

INTRODUCTION: Some patients with gastroparesis (Gp) report hair loss. The aim of this study was to investigate the prevalence of patient-reported hair loss in Gp patients, analyze hair loss association to severity of Gp and nutritional deficiencies, and study effects of multivitamin treatment on hair loss. METHODS: Patients with Gp were questioned about hair characteristics, Gp symptoms, and diet. Patients with hair loss had blood drawn for vitamin levels. Patients with hair loss were treated with daily multivitamin and assessed 8 weeks later. RESULTS: Hair loss was reported in 65 of 143 patients with Gp (45.5%), occurring similarly in idiopathic and diabetic Gp. Hair loss was most commonly noticed while washing and/or combing hair. Patients with hair loss had more severe nausea, abdominal pain, stomach fullness, loss of appetite, abdominal discomfort, bloating, retching, stomach distension, vomiting, early satiety, postprandial fullness, and constipation. Hair loss patients lost more weight over prior 6 months. Patients with hair loss had similar gastric retention on gastric emptying scintigraphy. Overall, 29 of 61 (47.5%) patients with hair loss had at least one abnormal bloodwork result. After 8 weeks of treatment with a daily multivitamin, 17 of 41 (41%) patients had improvement in hair loss. CONCLUSION: Hair loss occurred in 46% of patients with Gp, being associated with more severe symptoms, loss of weight, and several vitamin deficiencies, although not a specific one. Treatment with multivitamins improved hair loss in 40% of patients. Presence of hair loss in patients with Gp should prompt nutritional evaluation and supplementation.

Esophageal Inlet Patch: Association with Barrett's Esophagus.

BACKGROUND: Esophageal inlet patch (IP) with heterotopic gastric mucosa is an incidental finding on esophagogastroduodenoscopy (EGD). Although IP is thought to be embryologic in nature, IP has been associated with Barrett's esophagus (BE). AIMS: The aim of this study was to compare prevalence, symptoms, demographic factors, and esophageal testing in patients with IP and BE. METHODS: We retrospectively analyzed endoscopic findings of EGDs, high-resolution esophageal manometry and esophageal pH impedance studies from January 2010 to January 2021 at a single academic medical center. Patients were grouped by presence or absence of IP and BE. RESULTS: Of 27,498 patients evaluated, 1.3% had endoscopic evidence of IP and 4.9% had BE. Of 362 patients with IP, 17.1% had BE; of 1356 patients with BE, 4.6% had IP. Both IP and BE patients presented primarily with heartburn and/or regurgitation. Patients with BE and/or IP were older and had higher BMI than those without (p < 0.001). Mean lower esophageal sphincter pressure was lower and mean acid exposure time (AET) was higher in patients with IP and/or BE than those without (p < 0.05). CONCLUSIONS: Our study reports an IP prevalence of 1.3%, with 17.1% patients having concomitant BE; and a BE prevalence of 4.9%, with 4.6% also having IP. Patients with IP alone presented with similar symptoms to patients with concomitant BE. Esophageal function testing showed that patients with either IP or BE had decreased LES pressures and increased esophageal AET. During endoscopy, patients found to have one of these findings should be carefully examined for the other.

Postprandial symptoms in patients with symptoms of gastroparesis: roles of gastric emptying and accommodation.

Patients often are evaluated for gastroparesis because of symptoms occurring with meals. Gastric emptying scintigraphy (GES) is used for gastroparesis diagnosis, although results are not well correlated with gastroparesis symptoms. The aim of this study is to assess relationships between gastroparesis symptoms, gastric emptying (GE), and gastric accommodation (GA). Patients with symptoms of gastroparesis completed the Patient Assessment of Upper GI Symptoms (PAGI-SYM) and recorded symptoms during GES and water load satiety test (WLST), an indirect assessment for GA. A total of 109 patients with gastroparesis symptoms were assessed. Symptom severity increased after GES meal for stomach fullness, belching, nausea, abdominal burning, and abdominal pain. There was no difference in symptoms after meal between patients with delayed (n = 66) and normal (n = 42) GE. Diabetic patients (n = 26) had greater gastric retention than idiopathic patients (n = 78), but idiopathic patients had greater postprandial nausea, stomach fullness, and abdominal pain. Water consumed during WLST averaged 421 ± 245 mL. Idiopathic patients had greater nausea scores during WLST than diabetic patients. In comparison to those with normal water consumption (≥238 mL; n = 80), patients with impaired water ingestion (<238 mL; n = 26) had increased stomach fullness, early satiety, postprandial fullness, and loss of appetite on PAGI-SYM. Patients with delayed and normal GE had similar symptom profiles during GES and WLST. Idiopathic patients had less gastric retention but more symptoms after GES meal and after WLST compared with diabetic patients. Patients with impaired water consumption during WLST had increased symptoms by PAGI-SYM. These data suggest that impaired GA, rather than GE, may be important in explaining postprandial symptoms in patients with symptoms of gastroparesis.NEW & NOTEWORTHY Patients with delayed and normal gastric emptying (GE) had similar symptom profiles during gastric emptying scintigraphy (GES). Idiopathic patients with symptoms of gastroparesis had less gastric retention by GES; but more symptoms after GES meal and after water load satiety test (WLST) compared with diabetic patients. In patients with symptoms of gastroparesis, symptoms after WLST increased with decreasing water consumption. Early satiety and loss of appetite were associated with decreased water consumption during WLST. Thus, impaired accommodation and perhaps visceral hypersensitivity are important in explaining postprandial symptoms in gastroparesis.

Baseline Predictors of Longitudinal Changes in Symptom Severity and Quality of Life in Patients With Suspected Gastroparesis.

BACKGROUND & AIMS: Whether gastric emptying tests predict longitudinal outcomes in patients with symptoms of gastroparesis is unclear. We aimed to determine whether baseline gastric emptying tests and gut motility parameters could impact longitudinal symptom(s) and quality of life (QOL) in a prospective, observational cohort study of patients with symptoms of gastroparesis. METHODS: One hundred fifty patients with gastroparesis symptoms underwent simultaneous scintigraphy (GES) and wireless motility capsule (WMC) measurement of gastric emptying and other motility parameters. Patient Assessment of Upper Gastrointestinal Symptoms and Quality of Life were administered at baseline, and 3 and 6 months after testing. Multivariable generalized linear marginal models were fit to determine which baseline parameters predict longitudinal changes in symptoms and QOL. RESULTS: Overall upper GI symptoms and QOL scores were moderate in severity at baseline and significantly improved over 6 months. Clinical variables, including female gender, harder stools by Bristol stool form score, and presence of functional dyspepsia (FD) by Rome III criteria, were predictive of more severe upper GI symptoms. Even after controlling for these clinical factors, delayed gastric emptying by GES or WMC was associated with worse symptom severity and QOL scores. Low gastric and elevated small bowel contractile parameters by WMC were also independently associated with more severe upper GI symptoms and worse QOL scores. CONCLUSIONS: Baseline features, including demographic and clinical variables, delayed gastric emptying and abnormal gastrointestinal contractility, were independent predictors of more severe longitudinal symptoms and worse quality of life outcomes. These factors may help to risk stratify patients and guide treatment decisions. ClinicalTrials.gov no: NCT02022826.

Efficacy and Safety of Tradipitant in Patients With Diabetic and Idiopathic Gastroparesis in a Randomized, Placebo-Controlled Trial.

BACKGROUND & AIMS: Treatments are needed for gastroparesis; antagonists of tachykinin receptor 1 (TACR1, also called NK1R) can reduce symptoms of nausea and vomiting. We investigated the safety and efficacy of tradipitant, an antagonist of NK1R, in patients with idiopathic or diabetic gastroparesis. METHODS: We performed a double-blind trial of 152 adults with gastroparesis at 47 sites in the United States from November 2016 through December 2018. Participants were randomly assigned to groups given oral tradipitant 85 mg (n = 77) or placebo (n = 75) twice daily for 4 weeks. Symptoms were assessed by a daily symptom dairy, Gastroparesis Cardinal Symptom Index scores, and other patient-reported questionnaires. The primary outcome from the intent-to-treat analysis was change from baseline to week 4 in average nausea severity, measured by the Gastroparesis Core Symptom Daily Diary. RESULTS: Patients receiving tradipitant had a significant decrease in nausea score (reduction of 1.2) at week 4 compared with placebo (reduction of 0.7) (P = .0099) and a significant increase in of nausea-free days at week 4 (28.8% increase on tradipitant vs 15.0% on placebo; P = .0160). Patients with nausea and vomiting at baseline (n = 101) had an even greater decrease in nausea in when given tradipitant (reduction of 1.4) compared with those given placebo (reduction of 0.4) (P < .0001), as well as an increase in nausea-free days at week 4 (32.3% improvement on tradipitant vs 7.6% on placebo; P = .0003). The average nausea score was 1 or less at week 4 in 32.9% of patients given tradipitant compared with 11.8% of patients given placebo (P = .0013). A greater than 1-point improvement in Gastroparesis Cardinal Symptom Index score was observed in 46.6% of patients given tradipitant compared with 23.5% of patients given placebo (P = .0053). CONCLUSIONS: Tradipitant resulted in statistically and clinically meaningful improvements in nausea and reduced vomiting, compared with placebo, in patients with idiopathic or diabetic gastroparesis. ClinicalTrials.gov, Number: NCT02970968.

Progress in Gastroparesis - A Narrative Review of the Work of the Gastroparesis Clinical Research Consortium.

The Gastroparesis Clinical Research Consortium is a multicenter coalition created and funded by the National Institutes of Diabetes and Digestive and Kidney Disorders, with a mission to advance understanding of the pathophysiology of gastroparesis and develop an effective treatment for patients with symptomatic gastroparesis. In this review, we summarize the results of the published Gastroparesis Clinical Research Consortium studies as a ready and convenient resource for gastroenterologists and others to provide a clear understanding of the consortium's experience and perspective on gastroparesis and related disorders.

Effect of Domperidone Therapy on Gastroparesis Symptoms: Results of a Dynamic Cohort Study by NIDDK Gastroparesis Consortium.

BACKGROUND & AIMS: The use of domperidone (DOM) for gastroparesis (GP) remains controversial and limited. We aimed to present outcomes of DOM therapy for treatment of patients participating in the multicenter National Institute of Diabetes and Digestive and Kidney Diseases Gastroparesis Clinical Research Consortium (GpCRC) Registries (GpR). METHODS: The GpCRC cohort consisted of patients with GP (75%) and with GP-like symptoms but with normal gastric emptying (25%). The DOM group initiated therapy during the 96 weeks of enrollment in GpR1 and GpR2. Patients who had previously taken or who were on DOM therapy at enrollment were excluded from this analysis. The control group did not use domperidone (non-DOM group) before or after enrollment. The following outcome measures were identified: change from baseline in Gastroparesis Cardinal Symptom Index total score, with 3 subscales, plus Gastroesophageal Reflux Disease and Patient Assessment of Upper Gastrointestinal Disorders-Quality of Life scores. RESULTS: Overall, of 748 patients, 181 (24%) were in the DOM group, whereas 567 were in the non-DOM group. Sixty-three percent of participants had idiopathic GP. At baseline, DOM patients compared with non-DOM patients were significantly younger, had lower body mass index, non-Hispanic ethnicity, a higher annual household income, lower narcotic utilization, lower supplemental and complimentary medication use, and were more likely to have delayed gastric emptying time, as well as worse nausea and fullness scores. Compared with non-DOM patients, DOM patients experienced moderate but significantly more improvement in GP outcome measures: Gastroparesis Cardinal Symptom Index total score (P = .003), nausea (P = .003), and fullness subscales (P =.005), upper abdominal pain score (P = .04), Gastroesophageal Reflux Disease score (P = .05), and Patient Assessment of Upper Gastrointestinal Disorders-Quality of Life score (P = .05). CONCLUSIONS: Utilizing the method of pragmatic modeling to evaluate long-term treatment of GP in a large GpCRC database, DOM treatment resulted in moderately but significantly improved GP. NOTE: This project was based on data generated by 2 GpCRC Registry studies recognized under the Clinicaltrial.gov numbers: NCT00398801 and NCT01696747 symptoms compared with a group receiving standard-of-care but not DOM.

Constipation in Patients With Symptoms of Gastroparesis: Analysis of Symptoms and Gastrointestinal Transit.

BACKGROUND & AIMS: Constipation can be an important symptom in some patients with gastroparesis. The aims were to: 1) Determine prevalence of constipation and delayed colonic transit in patients with symptoms of gastroparesis; 2) Correlate severity of constipation to severity of symptoms of gastroparesis; and 3) Relate severity of constipation to GI transit delays assessed by gastric emptying scintigraphy (GES) and wireless motility capsule (WMC). METHODS: Patients with symptoms of gastroparesis underwent gastric emptying scintigraphy (GES), wireless motility capsule (WMC) assessing gastric emptying, small bowel transit, and colonic transit, and questionnaires assessing symptoms using a modified Patient Assessment of Upper GI Symptoms [PAGI-SYM] and Rome III functional GI disorder questionnaire. RESULTS: Of 338 patients with symptoms of gastroparesis, 242 (71.5%) had delayed gastric emptying by scintigraphy; 298 (88.2%) also met criteria for functional dyspepsia. Severity of constipation was severe/very severe in 34% patients, moderate in 24%, and none/very mild/mild in 42%. Increasing severity of constipation was associated with increasing symptoms of gastroparesis and presence of irritable bowel syndrome (IBS). Severity of constipation was not associated with gastric retention on GES or WMC. Delayed colonic transit was present in 108 patients (32% of patients). Increasing severity of constipation was associated with increasing small bowel transit time, colonic transit time, and whole gut transit time. CONCLUSIONS: Severe/very severe constipation and delayed colon transit occurs in a third of patients with symptoms of gastroparesis. The severity of constipation is associated with severity of gastroparesis symptoms, presence of IBS, small bowel and colon transit delay, but not delay in gastric emptying. ClinicalTrials.gov Identifier: NCT01696747.

Functional Dyspepsia and Gastroparesis in Tertiary Care are Interchangeable Syndromes With Common Clinical and Pathologic Features.

BACKGROUND: The aim of this study was to clarify the pathophysiology of functional dyspepsia (FD), a highly prevalent gastrointestinal syndrome, and its relationship with the better-understood syndrome of gastroparesis. METHODS: Adult patients with chronic upper gastrointestinal symptoms were followed up prospectively for 48 weeks in multi-center registry studies. Patients were classified as having gastroparesis if gastric emptying was delayed; if not, they were labeled as having FD if they met Rome III criteria. Study analysis was conducted using analysis of covariance and regression models. RESULTS: Of 944 patients enrolled during a 12-year period, 720 (76%) were in the gastroparesis group and 224 (24%) in the FD group. Baseline clinical characteristics and severity of upper gastrointestinal symptoms were highly similar. The 48-week clinical outcome was also similar but at this time 42% of patients with an initial diagnosis of gastroparesis were reclassified as FD based on gastric-emptying results at this time point; conversely, 37% of patients with FD were reclassified as having gastroparesis. Change in either direction was not associated with any difference in symptom severity changes. Full-thickness biopsies of the stomach showed loss of interstitial cells of Cajal and CD206+ macrophages in both groups compared with obese controls. CONCLUSIONS: A year after initial classification, patients with FD and gastroparesis, as seen in tertiary referral centers at least, are not distinguishable based on clinical and pathologic features or based on assessment of gastric emptying. Gastric-emptying results are labile and do not reliably capture the pathophysiology of clinical symptoms in either condition. FD and gastroparesis are unified by characteristic pathologic features and should be considered as part of the same spectrum of truly "organic" gastric neuromuscular disorders. CLINICALTRIALS. GOV IDENTIFIER: NCT00398801, NCT01696747.

Demographics of Gastroparesis Hospitalizations Through the Age Spectrum Using National Inpatient Databases: Children Compared With Adults.

GOAL: The goal of this study was to characterize the etiology and demographics of hospitalized patients with gastroparesis (Gp) across different age groups. BACKGROUND: Gp is a chronic condition associated with increasing hospitalizations and costs. The gender and etiology distributions of Gp throughout the age spectrum are unknown. MATERIALS AND METHODS: Nationwide Inpatient Sample (NIS) and Kid's Inpatient Database (KID) were used to identify patients using International Classification of Diseases (ICD)-10 codes for Gp as a primary diagnosis or as secondary diagnosis with the first diagnosis a GI-related symptom. RESULTS: There were a total of 15,790 admissions (75.6% female, age: 46.2±18.0 y). After age 6, female admissions percentage increased: ages 2 to 5: 45.0%, ages 6 to 12: 62.8%, ages 13 to 20: 76.7% ( P <0.001), with a distinct increase at age 12. Diabetic gastroparesis (DG) was seen in 3995 (25.3%) of all Gp admissions but in only 1.1% of children under the age of 20. Overall, 68% of DG admissions were female, but a higher percentage of DG was seen among male admissions for Gp compared with female admissions for Gp between ages 21 and 64 (38.3% vs. 23%, P <0.001). The most common races were white (63.2%), African American (20.6%), and Hispanic (8.7%). DG was more often present in Native American (61.9%), Hispanic (39.1%), and African American (38.2%) admissions than in white patients (17.8%; P <0.05). CONCLUSIONS: This study using large inpatient databases shows that the gender, race, and etiology of Gp admissions is age-dependent. The female predominance of Gp admissions is more prominent from the second decade of life. DG, although uncommon in children, is seen more often in nonwhite admissions.