MoPill a novel gastrointestinal positioning system (GPS): New technology to navigate the alimentary tract highway.

BACKGROUND: Evaluation of gut motility in clinical practice is currently limited. A novel medical system (MoPill™) consisting of a capsule that wirelessly transmits radiofrequency signals to assess motility via 3D location, was used to conduct this study. The objectives were to: (1) confirm the safety of the MoPill™ system; (2) compare the 3D location transmitted by the capsule to its location captured by abdominal x-rays; 3 determine gastric emptying (GE), whole gut transit time (WGTT) and segmental transit times. METHODS: The MoPill™ system consists of an electronic capsule (2 × 1.2 cm), eight color-coded adhesive sensors (6 × 5.5 cm), a recorder (15 × 11 × 2 cm), and software on a laptop. Four sensors were applied to the abdomen and four to the back. Healthy subjects who had fasted overnight ingested a 250-calorie protein bar, 17 oz. of water, followed by an activated capsule. No further caloric contents were permitted for the next 5 h. At 1, 5, and 24 h (if the capsule had not been expelled), upright abdominal X-rays (AP and lateral) were obtained to assess the location of the capsule, which was compared to the gastrointestinal positioning system (GPS) location determined by the MoPill™ system. Identification of the capsule's anatomical location by the MoPill™ system was based on (1) the 3D (x, y, z) location; (2) time; (3) trajectory (e.g., going up the right side of the body signified ascending colon); (4) frequency of contractions (e.g., 3 cycles/min for the stomach); and (5) milestone relationship (e.g., pyloric passage must follow the end of gastric contractions). GE was determined first by the end of the 3 cycles/min rhythmic movement of the stomach and then again by pyloric expulsion on 3D location. Small intestine transit was taken as the duration from pyloric expulsion to arrival in the cecum. Colon transit time was determined by calculating the duration from 3D arrival in the cecum to passage of the capsule out of the body (i.e., loss of signal accompanying a bowel movement). KEY RESULTS: Ten healthy subjects (five women; mean age 34; mean BMI 24) were enrolled, and nine provided reliable data. The variation between the x-ray and the estimated (i.e., identified by the MoPill™ system) location of the capsule was within an average of 3.5 cm (range 0.9-9.4 cm). The mean GE was 3.1 h. The small intestine's mean transit time was 4.3 h. The mean colonic transit time was 17.6 h. There were no adverse events recorded during the study. CONCLUSIONS & INFERENCES: MoPill™ is a novel gastrointestinal positional system that accurately identifies the location of a capsule compared to an X-ray. MoPill™ system also recognizes GE, small bowel, colonic, and WGTT as well as segmental gut location and movement characteristics. MoPill™ offers the potential for new insights into GI motility disorders not attainable by current modalities.

Examining linaclotide for the treatment of chronic idiopathic constipation.

INTRODUCTION: Chronic idiopathic constipation (CIC) is characterized by infrequent bowel movements and hard stools lasting for at least three months or longer. This disease affects 8-12% of the US population and 10-17% of the world population. Treatment and management involve identifying the primary cause, changing dietary habits, and adequate physical activity. Linaclotide is a guanylate cyclase-agonist acting locally in the luminal surface of the intestinal enterocyte leading to a signal transduction cascade, activation of the cystic fibrosis transmembrane conductance regulator (CFTR), thus increasing secretion of chloride and bicarbonate into the intestinal lumen with eventual increased intestinal fluid and faster transit time. AREAS COVERED: We reviewed multiple studies and did a thorough literature review on CIC including its pathophysiology. Through this literature review we were able to discuss and give the context and rationale for drug regimens indicated for CIC. EXPERT OPINION: The era we live in right now is akin to nutrient-rich and fertilized soil as knowledge and resources are abundant. The opportunities and potential are endless. Constipation being more extensively studied, our understanding of medications and diseases broadens, leading to novel medications being discovered. Linaclotide is a pioneer in this aspect and can pave the way for future generations.

Predicting Response to Neuromodulators or Prokinetics in Patients with Suspected Gastroparesis Using Machine Learning: the "BIDnD" Model.

INTRODUCTION: Pharmacologic therapies for symptoms of gastroparesis have limited efficacy and it is difficult to predict which patients will respond. In this study, we implemented a machine-learning model to predict the response to prokinetics and/or neuromodulators in patients with gastroparesis-like symptoms. METHODS: Subjects with suspected gastroparesis underwent simultaneous gastric emptying scintigraphy (GES) and wireless motility capsule (WMC) and were followed for 6 months. Subjects were included if they were started on neuromodulators and/or prokinetics. Subjects were considered responders if their Gastroparesis Cardinal Symptom Index (GCSI) at 6 months decreased by ≥1 from baseline. A machine-learning model was trained using lasso regression, ridge regression or random forest. Five-fold cross-validation was used to train the models and the area under the receiver operator characteristic curve (AUC-ROC) was calculated using the test set. RESULTS: Of the 150 patients enrolled, 123 patients received either a prokinetic and/or a neuromodulator. Of the 123, 45 were considered responders and 78 were non-responders. A ridge regression model with the variables: BMI, Infectious prodrome, delayed GES, no diabetes (BIDnD), had the highest AUC-ROC of 0.72. The model performed well for subjects on prokinetics without neuromodulators (AUC-ROC of 0.83) but poorly for those on neuromodulators without prokinetics. A separate model with GET, duodenal MI, no diabetes, and functional dyspepsia performed better (AUC-ROC of 0.75). DISCUSSION: This machine learning model has an acceptable accuracy in predicting those who will respond to neuromodulators and/or prokinetics. If validated, our model provides valuable data in predicting treatment outcomes in patients with gastroparesis-like symptoms.

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.

Current and emerging pharmacotherapy for the treatment of gastroparesis.

INTRODUCTION: Gastroparesis is a chronic disorder characterized by decreased gastric emptying and presents with nausea, vomiting, and abdominal pain which impacts patients' quality of life greatly. The treatment modalities available for gastroparesis have been expanding over the past 2 decades. Currently, there are multiple options available for gastroparesis, albeit with only one FDA-approved medication until June 2021. AREAS COVERED: We review the different treatments available for gastroparesis and discuss the recently FDA-approved intranasal formulation of metoclopramide. This nasal spray guarantees metoclopramide absorption within 15 min of application bypassing first pass metabolism in the liver and overcoming the limitations of the oral formulation not passing into the small intestine for absorption because of a gastroparetic stomach or a patient unable to take the oral metoclopramide because of nausea and vomiting. EXPERT OPINION: We now find ourselves in an oasis after spending many years in a 'desert' regarding pharmacologic therapies available for gastroparesis. The expansion of the research involving dopamine receptor antagonists and delving into alternative mechanisms of alleviating gastroparesis symptoms has been crucial in the landscape of gastroparesis. This is especially true as our knowledge of gastroparesis has proven that simply improving gastric emptying does not necessarily translate to clinical improvement.

AGA Clinical Practice Update on Diagnosis and Management of Cannabinoid Hyperemesis Syndrome: Commentary.

DESCRIPTION: The purpose of this American Gastroenterological Association (AGA) Institute Clinical Practice Update (CPU) is to review the available evidence and provide expert advice regarding diagnosis and management of cannabinoid hyperemesis syndrome. METHODS: This CPU was commissioned and approved by the AGA Institute Clinical Practice Updates Committee (CPUC) and the AGA Governing Board to provide timely guidance on a topic of high clinical importance to the AGA membership and underwent internal peer review by the CPUC and external peer review through standard procedures of Gastroenterology. This expert commentary incorporates important as well as recently published studies in this field, and it reflects the experiences of the authors.

Single cell atlas of human gastric muscle immune cells and macrophage-driven changes in idiopathic gastroparesis.

Gastrointestinal immune cells, particularly muscularis macrophages (MM) interact with the enteric nervous system and influence gastrointestinal motility. Here we determine the human gastric muscle immunome and its changes in patients with idiopathic gastroparesis (IG). Single cell sequencing was performed on 26,000 CD45+ cells obtained from the gastric tissue of 20 subjects. We demonstrate 11 immune cell clusters with T cells being most abundant followed by myeloid cells. The proportions of cells belonging to the 11 clusters were similar between IG and controls. However, 9/11 clusters showed 578-11,429 differentially expressed genes. In IG, MM had decreased expression of tissue-protective and microglial genes and increased the expression of monocyte trafficking and stromal activating genes. Furthermore, in IG, IL12 mediated JAK-STAT signaling involved in the activation of tissue-resident macrophages and Eph-ephrin signaling involved in monocyte chemotaxis were upregulated. Patients with IG had a greater abundance of monocyte-like cells. These data further link immune dysregulation to the pathophysiology of gastroparesis.

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.).

Cannabinoid hyperemesis syndrome: prevalence and management in an era of cannabis legalization.

As more states legalize cannabinoid products for recreational use and medicinal purposes, the prevalence of cannabinoid hyperemesis syndrome has become increasingly common. Yet, it remains unrecognized to many healthcare providers along with the most efficacious treatments. Cannabinoid hyperemesis syndrome most often presents with episodic vomiting secondary to chronic daily cannabis use over several months to years. Patients often complain of nausea and abdominal pain that is improved by taking hot showers or baths. Symptoms are alleviated with the cessation of cannabis use over a period of 6-12 months. Treatment for acute attacks often consists of parenteral benzodiazepines in the inpatient setting. Long-term management and prevention of further attacks are aided by tricyclic antidepressants such as amitriptyline with a dose range of 50-200 mg/d. Once a patient is in remission, amitriptyline can be tapered slowly. As cannabis becomes more widely available and accepted in the continental United States, so must education on the diagnosis of cannabinoid hyperemesis syndrome and treatment strategies.

The spectrum of gastrointestinal functional bowel disorders in joint hypermobility syndrome and in an academic referral center.

Joint hypermobility syndrome (JHS) is a non-inflammatory hereditary disorder of connective tissue with varied clinical presentations, including frequent joint dislocations, hyperextensible skin, easy bruising, and abnormal paper-thin scar formation. Many of these patients have unexplained gastrointestinal (GI) symptoms. Our aim was to evaluate the prevalence of JHS in a tertiary gastroenterology motility clinic and the spectrum of functional bowel disorders in JHS patients. In this retrospective case series, we screened the medical records of 277 patients seen over 4 years at an academic GI Motility Center. The patients who met the criteria for JHS by Beighton hypermobility score were evaluated for the presence of functional GI disorders by Rome IV criteria. They also underwent gastric emptying study and glucose breath testing for small intestinal bacterial overgrowth. The prevalence of JHS in the study population was 9.7%. The mean age was 27 years, and 92.5% were female. The symptoms experienced by these patients include nausea/vomiting (89%), abdominal pain (70%), constipation (48%), and bloating (18.5%). The disorders associated with JHS include gastroparesis (52%), irritable bowel syndrome (55.5%), and gastroesophageal reflux disease (30%). Also, 10 patients (37%) were diagnosed with postural hypotension tachycardia syndrome secondary to autonomic dysfunction. Approximately 10% of patients with suspected functional bowel disorders have hypermobility syndrome. Hence, it is crucial to familiarize gastrointestinal practitioners with the criteria utilized to diagnose JHS and the methods to identify physical examination findings related to this condition.

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.).

A pilot genome-wide association study meta-analysis of gastroparesis.

BACKGROUND: Gastroparesis (GP) is characterized by delayed gastric emptying in the absence of mechanical obstruction. OBJECTIVE: Genetic predisposition may play a role; however, investigation at the genome-wide level has not been performed. METHODS: We carried out a genome-wide association study (GWAS) meta-analysis on (i) 478 GP patients from the National Institute of Diabetes and Digestive and Kidney Diseases Gastroparesis Clinical Research Consortium (GpCRC) compared to 9931 population-based controls from the University of Michigan Health and Retirement Study; and (ii) 402 GP cases compared to 48,340 non-gastroparesis controls from the Michigan Genomics Initiative. Associations for 5,811,784 high-quality SNPs were tested on a total of 880 GP patients and 58,271 controls, using logistic mixed models adjusted for age, sex, and principal components. Gene mapping was obtained based on genomic position and expression quantitative trait loci, and a gene-set network enrichment analysis was performed. Genetic associations with clinical data were tested in GpCRC patients. Protein expression of selected candidate genes was determined in full thickness gastric biopsies from GpCRC patients and controls. RESULTS: While no SNP associations were detected at strict significance (p ≤ 5 × 10-8 ), nine independent genomic loci were associated at suggestive significance (p ≤ 1 × 10-5 ), with the strongest signal (rs9273363, odds ratio = 1.4, p = 1 × 10-7 ) mapped to the human leukocyte antigen region. Computational annotation of suggestive risk loci identified 14 protein-coding candidate genes. Gene-set network enrichment analysis revealed pathways potentially involved in immune and motor dysregulation (pFDR ≤ 0.05). The GP risk allele rs6984536A (Peroxidasin-Like; PXDNL) was associated with increased abdominal pain severity scores (Beta = 0.13, p = 0.03). Gastric muscularis expression of PXDNL also positively correlated with abdominal pain in GP patients (r = 0.8, p = 0.02). Dickkopf WNT Signaling Pathway Inhibitor 1 showed decreased expression in diabetic GP patients (p = 0.005 vs. controls). CONCLUSION: We report preliminary GWAS findings for GP, which highlight candidate genes and pathways related to immune and sensory-motor dysregulation. Larger studies are needed to validate and expand these findings in independent datasets.

Gastric Electrical Stimulation as a New Treatment Modality for Refractory Nausea and Vomiting with Normal Gastric Emptying.

Nausea and vomiting are cardinal symptoms affecting many patients with delayed or normal gastric emptying. The current therapies are very limited and less than optimal. Therefore, gastrointestinal symptoms persist despite using all the standard approaches for gastroparesis, functional dyspepsia, or unexplained nausea and vomiting. It is well established that gastric electrical stimulation (GES) is effective in reducing nausea and vomiting in gastroparesis, but there are essentially no data available that detail the efficacy of GES in symptomatic patients without gastroparesis. We present a unique case of a female patient diagnosed with functional dyspepsia, whose nausea and vomiting which were refractory to all standard therapies were successfully addressed with the implantation of a GES system.

Randomized clinical trial: A phase 2b controlled study of the efficacy and safety of trazpiroben (TAK-906) for idiopathic or diabetic gastroparesis.

BACKGROUND: Previous clinical studies of trazpiroben, a dopamine D2 /D3 receptor antagonist for long-term treatment of moderate-to-severe idiopathic and diabetic gastroparesis, have shown improved symptoms of fullness. This study assessed trazpiroben efficacy, safety, and tolerability in adults with idiopathic and diabetic gastroparesis versus placebo. METHODS: This global, multicenter, double-blind, parallel-group, phase 2b study (NCT03544229) enrolled eligible adults aged 18-85 years with symptomatic idiopathic or diabetic gastroparesis. Randomized participants received either oral placebo or trazpiroben 5, 25, or 50 mg, administered twice daily over 12 weeks, and completed the American Neurogastroenterology and Motility Society Gastroparesis Cardinal Symptom Index-Daily Diary. Change in weekly composite score from baseline to week 12 (primary endpoint) and treatment-emergent adverse events were assessed. Data were summarized descriptively. KEY RESULTS: Overall, 242 participants were enrolled (mean [standard deviation] age 55.7 [14.2] years; 75.6% female); 193 completed the study. No significant differences in change from baseline in weekly average of the daily diary composite score occurred at week 12 between placebo (least-squares mean [standard error] -1.19 [0.12]) and trazpiroben (5, 25, and 50 mg: -1.11 [0.22], -1.17 [0.12], and -1.21 [0.12], respectively). Overall, 41.4% of participants receiving trazpiroben reported treatment-emergent adverse events (placebo, 39.7%). No serious events were considered trazpiroben-related; no life-threatening or fatal events were reported. CONCLUSIONS & INFERENCES: There was no clinically meaningful difference in efficacy between trazpiroben and placebo in treating gastroparesis, based on the primary endpoint analysis. Trazpiroben was well tolerated with no new safety concerns identified, strengthening evidence supporting its favorable safety profile. NCT number: NCT03544229.

Plasma endocannabinoids and cannabimimetic fatty acid derivatives are altered in cyclic vomiting syndrome: The effects of sham feeding.

Cyclic vomiting syndrome (CVS) is an underdiagnosed disorder of the gut-brain interaction. Our understanding of the pathophysiology of CVS is evolving. Here, we tested the hypotheses that: (1) the levels of endocannabinoids and related lipids are altered in CVS, and (2) cephalic-vagal stimulation drive changes in endolipid levels. Ten adult patients with CVS and eight healthy controls were included. Indirect measurements of parasympathetic (RFa) functions were performed with spectral analysis of heart rate variability and respiratory activity. Plasma levels of endocannabinoids and related lipids were measured at baseline and during a sham feeding. Values are reported as mean ± standard error of the mean and compared using t-test or ANOVA. CVS patients had a lower parasympathetic tone and response to the Valsalva maneuver and deep breathing than the controls. The baseline 2-Arachidonoylglycerol (2-AG) had a significantly higher concentration in CVS (5.9e-008 ± 3.7e-008 mol/L) than control (3.7e-008 ± 1.3e-008 mol/; p < 0.05). Sham feeding did not change the concentration of 2-AG. 2-oleoylglycerol (2-OG) was significantly higher in CVS than control and did not change with sham feeding. Levels of N-acylethanolamines, including anandamide (AEA), were not different in CVS vs control. After sham feeding, AEA showed a trend toward increasing (p = 0.08) in CVS, but not in control. With sham feeding, palmitoyl ethanolamine significantly increased in both CVS and control groups; oleoyl ethanolamine in CVS only, and stearoyl ethanolamine in the control group. Levels of endocannabinoids and related lipids are altered in CVS patients. Sham feeding affects endogenous signaling lipids in a disease and time-dependent manner.

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.

Buspirone for early satiety and symptoms of gastroparesis: A multi-centre, randomised, placebo-controlled, double-masked trial (BESST).

BACKGROUND: Patients with gastroparesis and related disorders have symptoms including early satiety, postprandial fullness and bloating. Buspirone, a 5-HT1 receptor agonist, may improve fundic accommodation. AIM: To determine if buspirone treatment improves early satiety and postprandial fullness in patients with symptoms of gastroparesis. METHODS: This 4-week multi-centre clinical trial randomised patients with symptoms of gastroparesis and moderate-to-severe symptoms of fullness (Gastroparesis Cardinal Symptom Index [GCSI] early satiety/postprandial fullness subscore [ES/PPF]) to buspirone (10 mg orally) or placebo three times per day. The primary outcome was a change in the ES/PPF from baseline to 4 weeks. The primary analysis was per protocol intention-to-treat ANCOVA of between-group baseline vs. 4-week differences (DoD) in ES/PPF adjusted for baseline ES/PPF. Results are reported using both nominal and Bonferroni (BF) p values. RESULTS AND CONCLUSIONS: Ninety-six patients (47 buspirone, 49 placeboes; 92% female, 50% delayed gastric emptying, 39% diabetic) were enrolled. There was no between-groups difference in the 4-week ES/PPF primary outcome: -1.16 ± 1.25 (SD) on buspirone vs -1.03 ± 1.29 (SD) on placebo (mean DoD: -0.11 [95% CI: -0.68, 0.45]; p = 0.69). Buspirone performed better than placebo in patients with severe-to-very severe bloating at baseline compared to patients with none to moderate: (ES/PPF DoD = -0.65 vs. 1.58, pTX*GROUP  = 0.003; pBF  = 0.07). Among individual GCSI symptoms, only bloating appeared to improve with buspirone vs. placebo. CONCLUSIONS: Patients with moderate-to-severe early satiety/postprandial fullness and other symptoms of gastroparesis did not benefit from buspirone treatment to improve the ES/PPF primary outcome compared with placebo. There was a suggestion of the benefit of buspirone in patients with more severe bloating. TRIAL REGISTRATION: ClinicalTrials.gov NCT0358714285.

Characteristics and outcomes of patients with gastroparesis using enteral and/or exclusive parenteral nutrition.

BACKGROUND: Patients with gastroparesis (Gp) may need enteral nutrition (EN) or exclusive parenteral nutrition (PN). Among patients with Gp, we aimed to (1) identify the frequency of EN and exclusive PN use and (2) explore characteristics of patients using EN and/or exclusive PN compared with those using oral nutrition (ON), including changes over 48 weeks. METHODS: Patients with Gp underwent history and physical examination, gastric emptying scintigraphy, water load satiety testing (WLST), and questionnaires assessing gastrointestinal symptoms and quality of life (QOL). Patients were observed 48 weeks. RESULTS: Of 971 patients with Gp (idiopathic, 579; diabetic, 336; post-Nissen fundoplication, 51), 939 (96.7%) were using ON only, 14 (1.4%) using exclusive PN, and 18 (1.9%) using EN. Compared with patients receiving ON, patients receiving exclusive PN and/or EN were younger, had lower body mass index, and had greater symptom severity. Patients receiving exclusive PN and/or EN had lower physical QOL but not mental QOL or Gp-related QOL scores. Patients receiving exclusive PN and/or EN ingested less water during WLST but did not have worse gastric emptying. Of those who had been receiving exclusive PN and/or EN, 50% and 25%, respectively, resumed ON at 48-week follow-up. CONCLUSIONS: This study describes patients with Gp requiring exclusive PN and/or EN for nutrition support, who represent a small (3.3%) but important subset of patients with Gp. Unique clinical and physiological parameters are associated with this subset and provide insight into the use of nutrition support in Gp.

A randomized, double-blind, placebo-controlled, phase 2b study of the efficacy and safety of velusetrag in subjects with diabetic or idiopathic gastroparesis.

BACKGROUND: This study assessed the efficacy and safety of velusetrag-a 5-HT4 agonist with pan-gastrointestinal prokinetic activity-for gastroparesis symptom management and gastric emptying (GE). METHODS: In this multicenter, double-blind, randomized, placebo-controlled study, subjects with diabetic or idiopathic gastroparesis received velusetrag 5, 15, or 30 mg or placebo for 12 weeks. The primary efficacy outcome was a 7-day mean Gastroparesis Cardinal Symptom Index 24-h composite score (GCSI-24H) change from baseline at week 4; GE was evaluated using scintigraphy (GES) and breath tests, and safety from adverse events (AEs). KEY RESULTS: 232 subjects (183 females; 113 idiopathic gastroparesis) received treatment from February 2015 through June 2017. Least-squares mean improvement from baseline GCSI-24H (primary endpoint) at week 4 was -1.5 following velusetrag 5 mg vs -1.1 following placebo (treatment difference, -0.4; 95% confidence interval, -0.75 to -0.03; nominal p = 0.0327; Hochberg-adjusted p = 0.0980 [not significant]). Symptom improvement from baseline was achieved only with velusetrag 5 mg, which resulted in greater improvement from baseline vs placebo in all gastroparesis core symptoms, especially in subjects with idiopathic gastroparesis. Improvement from baseline GE by GES was greater in subjects receiving velusetrag (all doses) vs placebo; >70% of subjects receiving velusetrag 30 mg had GE normalization at 4 h. Treatment-emergent AEs were generally mild. CONCLUSIONS AND INFERENCES: Velusetrag treatment was generally well-tolerated and associated with improved GE vs placebo in subjects with diabetic or idiopathic gastroparesis; however, only the lowest dose, velusetrag 5 mg, was associated with short-term improvement in gastroparesis symptoms. CLINICALTRIALS: GOV: NCT02267525.