The Efficacy of Tradipitant in Patients With Diabetic and Idiopathic Gastroparesis in a Phase 3 Randomized Placebo-Controlled Clinical Trial.

BACKGROUND: Neurokinin receptor 1 antagonists are effective in reducing nausea and vomiting in chemotherapy-induced emesis. We investigated the safety and efficacy of tradipitant, a neurokinin receptor 1 antagonist, in patients with idiopathic and diabetic gastroparesis. METHODS: A total of 201 adults with gastroparesis were randomly assigned to oral tradipitant 85 mg (n = 102) or placebo (n = 99) twice daily for 12 weeks. Symptoms were assessed by a daily symptom dairy, Gastroparesis Cardinal Symptom Index scores, and other patient-reported questionnaires. Blood levels were monitored for an exposure-response analysis. The primary outcome was change from baseline to week 12 in average nausea severity, measured by daily symptom diary. RESULTS: The intention-to-treat (ITT) population did not meet the prespecified primary endpoint at week 12 (difference in nausea severity change drug vs placebo; P = .741) or prespecified secondary endpoints. Post hoc analyses were performed to control for drug exposure, rescue medications, and baseline severity inflation. Subjects with high blood levels of tradipitant significantly improved average nausea severity beginning at early time points (weeks 2-4). In post hoc sensitivity analyses, tradipitant treatment demonstrated strengthened effects, with statistically significant improvements in nausea at week 12. CONCLUSIONS: Although tradipitant did not reach significance in the ITT population, a pharmacokinetic exposure-response analysis demonstrated significant effects with adequate tradipitant exposure. When accounting for confounding factors such as baseline severity inflation and rescue medication, a statistically significant effect was also observed. These findings suggest that tradipitant has potential as a treatment for the symptom of nausea in gastroparesis. (ClincialTrials.gov, Number: NCT04028492).

Efficacy and Safety of Gastric Peroral Endoscopic Myotomy Across Different Etiologies of Gastroparesis: A Systematic Review and Meta-Analysis.

BACKGROUND AND AIMS: Gastric Peroral Endoscopic Myotomy (G-POEM) is an emerging treatment for refractory gastroparesis. While its efficacy and safety have been analyzed in previous systematic reviews and meta-analyses, no studies have compared its effectiveness based on etiology. Our study aims to evaluate the efficacy and safety of G-POEM by etiologies of gastroparesis. METHODS: We conducted a comprehensive search in major databases until October 2023, focusing on the efficacy and safety of G-POEM by etiology. Our primary outcome was clinical success based on etiology, with additional subgroup analysis on pre-and post-GCSI scores based on etiology using standard meta-analysis methods and the random-effects model. Heterogeneity was assessed using I2% statistics. RESULTS: In our analysis of 15 studies (7 retrospective, 8 prospective) involving 982 patients (mean age 50.81 years, mean follow-up 21 months), post-surgical conditions were the most common etiology in G-POEM (290 cases), followed by idiopathic factors (287 cases) and diabetes (286 cases). Subgroup analysis revealed pooled clinical success rates of 65% (CI: 51-77; I2 = 46%) for diabetes, 70% (CI: 46-86; I2 = 73%) for post-surgical, and 60% (CI: 41-77; I2 = 68%) for idiopathic etiologies. Our research also indicated that G-POEM significantly improved GCSI scores: 1.7 (95% CI: -0.01 to 3.5, p = 0.052) for diabetes, 1.34 (95% CI: -0.07 to 2.62, p = 0.038) for post-surgical, and 1.5 (95% CI: 0.36 to 2.75, p = 0.01) for idiopathic patients. CONCLUSION: Based on this meta-analysis, G-POEM is effective and safe for treating refractory gastroparesis irrespective of the etiology, with significant improvements in clinical success rates and GCSI scores.

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.

Both gastric electrical stimulation and pyloric surgery offer long-term symptom improvement in patients with gastroparesis.

BACKGROUND: Gastroparesis (GP) is hallmarked by nausea, vomiting, and early satiety. While dietary and medical therapy are the mainstay of treatment, surgery has been used to palliate symptoms. Two established first-line surgical options are gastric electrostimulation (GES) and pyloric procedures (PP) including pyloroplasty or pyloromyotomy. We sought to compare these modalities' improvement in Gastroparesis cardinal symptom index (GCSI) subscores and potential predictors of therapy failure. METHODS: All patients undergoing surgery at a single institution were prospectively identified and separated by surgery: GES, PP, or combined GESPP. GCSI was collected preoperatively, at 6 weeks and 1 year. Postoperative GCSI score over 2.5 or receipt of another gastroparesis operation were considered treatment failures. Groups were compared using Pearson's chi-squared and Kruskal-Wallis one-way ANOVA. RESULTS: Eighty-two patients were included: 18 GES, 51 PP, and 13 GESPP. Mean age was 44, BMI was 26.7, and 80% were female. Preoperative GCSI was 3.7. The PP group was older with more postsurgical gastroparesis. More patients with diabetes underwent GESPP. Preoperative symptom scores and gastric emptying were similar among all groups. All surgical therapies resulted in a significantly improved GCSI and nausea/vomiting subscore at 6 weeks and 1 year. Bloating improved initially, but relapsed in the GES and GESPP group. Satiety improved initially, but relapsed in the PP group. Fifty-nine (72%) had surgical success. Ten underwent additional surgery (7 crossed into the GESPP group, 3 underwent gastric resection). Treatment failures had higher preoperative GCSI, bloating, and satiety scores. Treatment failures and successes had similar preoperative gastric emptying. CONCLUSIONS: Both gastric electrical stimulation and pyloric surgery are successful gastroparesis treatments, with durable improvement in nausea and vomiting. Choice of operation should be guided by patient characteristics and discussion of surgical risks and benefits. Combination GESPP does not appear to confer an advantage over GES or PP alone.

Feasibility, safety, and long-term efficacy of gastric peroral endoscopic myotomy (G-POEM) for postsurgical gastroparesis: a single-center and retrospective study of a prospective database.

BACKGROUND: Postsurgical gastroparesis is recognized as a gastrointestinal dysfunction syndrome following foregut surgery. Gastric peroral endoscopic myotomy (G-POEM) is suggested as a minimally invasive therapy for gastroparesis. But the long-term efficacy and safety of G-POEM in treating postsurgical gastroparesis are rarely explored. METHODS: The primary outcomes included the symptomatic improvement based on gastroparesis cardinal symptoms index (GCSI) and the improvement of gastric emptying. The secondary outcomes included the improvement of gastroesophageal reflux symptoms and complications of G-POEM. RESULTS: The severity of postsurgical gastroparesis was not associated with the onset time and the course of the disease. G-POEM significantly reduced GCSI throughout the follow-up period (p < 0.0001). For different anastomotic site, a significant improvement of GCSI was found at 6 month post-G-POEM (F4,165 = 74.18, p < 0.0001). Subscale analysis of GCSI showed that nausea/vomiting, post-prandial fullness/early satiety, and bloating were improved significantly at 6-month post-G-POEM (p < 0.0001, respectively). Half-emptying and whole-emptying time were significantly shortened in patients with different anastomotic site post-G-POEM (half-emptying time: F3,174 = 65.44, p < 0.0001; whole-emptying time: F3,174 = 54.85, p < 0.0001). The emptying of ioversol was obviously accelerated after G-POEM. GCSI wasn't related to pyloric length, pyloric diameter, and thickness of pyloric wall. GERDQ was also used to evaluate the clinical efficacy of G-POEM. For each time points, GERDQ didn't differ significantly in patients with different anastomotic site (F4,104 = 0.8075, p = 0.5231). For patients with different anastomotic site, GERDQ was improved significantly at different time points (F4,104 = 59.11, p < 0.0001). The higher the esophageal anastomotic site was, the faster G-POEM improved the symptoms of gastroesophageal reflux. No one required re-hospitalization for any complication. CONCLUSION: G-POEM is a minimally invasive therapy with long-term effectiveness and safety in treating postsurgical gastroparesis.

Spatial Patterns From High-Resolution Electrogastrography Correlate With Severity of Symptoms in Patients With Functional Dyspepsia and Gastroparesis.

BACKGROUND & AIMS: Invasive gastric electrical mapping has revealed spatial abnormalities of the slow wave in subjects with gastroparesis and functional gastrointestinal disorders. Cutaneous high-resolution electrogastrography (HR-EGG) is a non-invasive method that can detect spatial features of the gastric slow wave. We performed HR-EGG in subjects with active foregut symptoms to evaluate associations between gastric myoelectric abnormalities, symptoms (based on a validated questionnaire), and gastric emptying. METHODS: We performed a case-control study of 32 subjects, including 7 healthy individuals (controls), 7 subjects with functional dyspepsia and normal gastric emptying, and 18 subjects with gastroparesis, from a tertiary care program. All subjects were assessed by computed tomography imaging of the abdomen and HR-EGG and completed the PAGI-SYM questionnaire on foregut symptoms, which includes the gastroparesis cardinal symptom index. We performed volume reconstruction of the torso and stomach from computed tomography images to guide accurate placement of the HR-EGG array. RESULTS: Spatial slow-wave abnormalities were detected in 44% of subjects with foregut symptoms. Moreover, subjects with a higher percentage of slow waves with aberrant propagation direction had a higher total gastroparesis cardinal symptom index score (r = 0.56; P < .001) and more severe abdominal pain (r = 0.46; P = .009). We found no correlation between symptoms and traditional EGG parameters. CONCLUSIONS: In case-control study, we found that the genesis of symptoms of functional dyspepsia and gastroparesis is likely multifactorial, including possible contribution from gastric myoelectric dysfunction. Abnormal spatial parameters, detected by cutaneous HR-EGG, correlated with severity of upper gastrointestinal symptoms, regardless of gastric emptying. This noninvasive, repeatable approach might be used to identify patients for whom gastric myoelectric dysfunction contributes to functional dyspepsia and gastroparesis.

Prevalence and severity of symptoms suggestive of gastroparesis in prodromal dementia with Lewy bodies.

INTRODUCTION: Lewy body disease is postulated, by the Braak model, to originate in the enteric nervous system, before spreading to the central nervous system. Therefore, a high prevalence of gastroparesis symptoms would be expected in prodromal dementia with Lewy bodies (DLB) and be highest in those with a dopaminergic deficit on imaging. The aim of this study was to explore whether gastroparesis symptoms are an early diagnostic marker of prodromal DLB and explore the relationship between symptoms and dopaminergic imaging findings on FP-CIT SPECT. METHODS: We recruited 75 patients over 60 with mild cognitive impairment (MCI), 48 with MCI with suspected Lewy body disease (MCI-LB) and 27 with MCI with suspected Alzheimer's disease (MCI-AD). All patients completed the Gastroparesis Cardinal Symptom Index (GSCI) questionnaire and also underwent FP-CIT [123 I-N-fluoropropyl-2ß-carbomethoxy-3ß-(4-iodophenyl)] dopaminergic imaging. RESULTS: At least one symptom suggestive of gastroparesis was reported in 48% (n = 23) MCI-LB vs 37% MCI-AD (n = 10) (P = 0.36). Rates of definite symptoms of gastroparesis, as defined by a GCSI total score ≥ 1.90, were rare and rates in MCI-LB were not different from MCI-AD (6% vs 0%, p = 0.55). After adjusting for gender differences between groups, no difference in gastroparesis symptom prevalence (2.27 vs 0.81 P = 0.05) or severity score (0.62 vs 0.28, p = 0.28) was noted between normally and abnormally visually rated FP-CIT SPECT scans. CONCLUSION: The GCSI is not a useful tool for differentiating MCI-LB from MCI-AD. A low rate of definite gastroparesis was detected in prodromal DLB. No association was found between gastroparesis symptoms and FP-CIT SPECT findings.

Functional Dyspepsia: Clinical Symptoms, Psychological Findings, and GCSI Scores.

BACKGROUND: The GCSI questionnaire measures symptoms of gastroparesis (GP). Symptoms of FD overlap with GP. The ability of the GCSI to discriminate FD from GP is unknown. AIMS: By prospectively evaluating functional dyspepsia (FD) patients, we aimed to evaluate the ability of the Gastroparesis Cardinal Symptom Index (GCSI) to: (1) distinguish FD from GP; (2) predict symptom severity, anxiety, and depression; (3) correlate symptoms with gastric emptying. METHODS: FD patients (Rome III criteria) were identified, and upper endoscopy and gastric emptying scan (GES) data recorded. A total of 254 patients were mailed a questionnaire evaluating demographics, FD symptoms, mental well-being; the GCSI was included. RESULTS: One hundred and twenty-three patients responded; of them, 75% were women and mean age was 49 (15 SD) years. 44.7% were categorized as postprandial distress subtype (PDS), 34.1% were epigastric pain subtype (EPS), and 21.1% were mixed type. The mean GCSI score was 2.02 (1.1 SD), slightly lower than historical GP controls (2.26-2.56). Mixed EPS-PDS subtype had the lowest GCSI scores (1.79; 0.91 SD). Bloating was the highest GCSI subscore (2.70; 1.53 SD), followed by fullness (2.31; 1.39 SD) and nausea (1.08; 1.19 SD). The GCSI total score did not correlate with anxiety and depression scores or with 4-h gastric emptying. CONCLUSIONS: In this population of FD patients, GCSI scores were slightly lower than historical gastroparesis control patients, although within the reported range. These results suggest that the GCSI cannot accurately distinguish FD patients from GP patients. A more specific questionnaire is needed to aid in the diagnosis and management of these distinct gastrointestinal disorders.

Nausea predicts delayed gastric emptying in children.

OBJECTIVES: To assess whether the gastroparesis cardinal symptom index (GCSI), or any individual symptom, is associated with delayed gastric emptying in children, and to assess understanding of symptoms associated with delayed gastric emptying. STUDY DESIGN: Fifty children (36 F), 5-18 years of age, undergoing gastric emptying scintigraphy (GES) at Lurie Children's Hospital in Chicago, Illinois, completed Likert-type GCSI and symptom comprehension questionnaires. Correlation of GES results (normal or abnormal) with questionnaire results using the Wilcoxon rank sum test. RESULTS: Seventy percent of subjects had a normal GES. Children reported understanding most terms of GCSI (average score 2.59, range 0-3). The GCSI was not associated with delayed gastric emptying. Nausea was associated with delayed gastric emptying only (numerical P = .04, word P = .02). Results were not altered when poorly understood terms were excluded. CONCLUSIONS: The GCSI is not associated with delayed gastric emptying in children. Lack of association does not seem to be related to lack of understanding. Nausea alone was the only symptom that showed an association with delayed gastric emptying on GES.

Symptoms from the Gastroparesis Cardinal Symptom Index and clinical factors associated with delayed gastric emptying in patients with suspected gastroparesis.

BACKGROUND: The association between upper gastrointestinal symptoms and delayed gastric emptying (GE) shows conflicting results. This study aimed to assess whether the symptoms of the Gastroparesis Cardinal Symptom Index (GCSI) and/or the scores were associated with the result of GE tests and whether they could predict delayed GE. METHODS: Patients referred for suspected gastroparesis (GP) were included in a prospective database. Demographical data, medical history, and symptoms of the GCSI score were collected for each patient. A GE scintigraphy was then performed with a 4-hour recording. Delayed GE was defined as a retention rate ≥ 10% at 4 h. RESULTS: Among 243 patients included in this study, 110 patients (45%) had delayed GE. The mean age (49.9 vs. 41.3 years; p < 0.001) and weight loss (9.4 kg vs. 5.6 kg; p = 0.025) were significantly higher in patients with delayed GE. Patients with diabetes or a history of surgery had a higher prevalence of delayed GE (60% and 78%, respectively) than patients without comorbidity (17%; p < 0.001). The GCSI score was higher in patients with delayed GE (3.06 vs. 2.80; p = 0.045), but no threshold was clinically relevant to discriminate between patients with normal and delayed GE. Only vomiting severity was significantly higher in patients with delayed GE (2.19 vs. 1.57; p = 0.01). CONCLUSION: GE testing should be considered when there are symptoms such as a higher weight loss, comorbidities (diabetes, and history of surgery associated with GP), and the presence of vomiting. Other symptoms and the GCSI score are not useful in predicting delayed GE.

Gastrointestinal symptom burden in diabetic autonomic and peripheral neuropathy - A Danes cohort study.

OBJECTIVE: We investigated associations between gastrointestinal symptoms - evaluated as a combined weighted symptom score (CWSS) - Diabetic autonomic neuropathy (DAN), and distal symmetrical polyneuropathy (DSPN) in type 1 and type 2 diabetes. RESEARCH DESIGN AND METHODS: Cross-sectional study in a tertiary outpatient clinic. CWSS was calculated based on questionnaires: gastroparesis composite symptom index (GCSI) and gastrointestinal symptom rating score (GSRS). DAN and DSPN were addressed using the composite autonomic symptom score 31 (COMPASS-31) questionnaire, cardiac autonomic reflex tests (CARTs), electrochemical skin conductance (ESC), vibration perception threshold (VPT), Michigan Neuropathy Screening Instrument (MNSI), pain- and thermal sensation. Analyses were adjusted for age, sex, diabetes duration, smoking, LDL-cholesterol, HbA1C and systolic blood pressure. Type 1 and type 2 diabetes were evaluated separately. RESULTS: We included 566 with type 1 diabetes and 377 with type 2 diabetes. Mean ± SD age was 58 ± 15 years and 565 (59.9 %) were women. A high CWSS was present in 143 (25 %) with type 1 and 142 (38 %) with type 2 diabetes. The odds of DAN by COMPASS-31 (p < 0.001) were higher in the high score group. For type 1 diabetes, odds of cardiac autonomic neuropathy were higher in the high CWSS group. The odds of DSPN by VPT and MNSI in type 1 diabetes, and by ESC, VPT and pain sensation in type 2 diabetes were higher in the high CWSS group. CONCLUSIONS: A high symptom score was associated with neuropathy by COMPASS-31 and vibration perception. Gastrointestinal symptom burden associated inconsistently with other neuropathy tests between diabetes types.

Efficacy of Pistacia lentiscus Plant (Rumi Mastagi) in Comparison to Levosulpiride in Patients with Diabetic Gastroparesis: A Double-Blind Non-Inferior Randomised Control Trial Study.

Introduction: Gastrointestinal neuropathies are frequently found in diabetic patients. The pathogenesis of diabetic gastroparesis (DG) is multifactorial. The usual treatment for DG includes dietary modifications, prokinetic and antiemetic agents. There is increasing demand for more effective medicines to treat DG. The current study was conducted on the Pistacia lentiscus stem extract to add to the armamentarium of DG treatment and to find the efficacy of P. lentiscus plant extract (mastic gum) in comparison to levosulpiride in DG for improvement in gastroparesis symptoms and gastric emptying scintigraphy (GES) in a single centric double-blind non-inferiority randomised control trial. Methods: Thirty-eight individuals were recruited and equally randomised into two study groups based on Gastroparesis Cardinal Symptom Index (GCSI) score and TC99 Radionuclide GES, mastic gum group and levosulpiride group. Both pre and post-intervention (8 weeks) GCSI scores were calculated, GES was performed to quantify the improvement in gastric emptying. Power analysis was performed using G*POWER software version 3.1.9.7 and data analysis using SPSS 23.0, variables measured in mean ± standard deviation (SD). Various statistical tests were used such as independent t-test, Chi-square test or Fisher's exact test, Wilcox Mann-Whitney test, analysis of variance (ANOVA) test, and posthoc pairwise tests. Results: The mastic gum is found effective in the improvement of 4 h gastric emptying percentage from the mean (SD) 76.60 (± 9.96) to mean (SD) 97.20 (2.17)% (P < 0.001). Mastic gum has the property of HbA1c reduction, which is more significant than that of levosulpiride (P = 0.044). Mastic gum also had significant Low density lipoprotein (LDL) (mg/dL) levels reduction, (P < 0.001), compared to levosupiride. An absolute increase was observed in haemoglobin (HB) level in mastic gum at a 2-month mean (SD) of 1.03 (0.77) (g/dL) (P-value <0.001). Conclusions: To our knowledge, this is the first study to compare the effect of levosulpiride with mastic gum concerning improvement in diabetic gastroparesis (DG) using GES. In the study, mastic gum was found to have great properties to improve DG with many important pleiotropic effects.

The ghrelin agonist RM-131 accelerates gastric emptying of solids and reduces symptoms in patients with type 1 diabetes mellitus.

BACKGROUND & AIMS: RM-131, a synthetic ghrelin agonist, greatly accelerates gastric emptying of solids in patients with type 2 diabetes and delayed gastric emptying (DGE). We investigated the safety and effects of a single dose of RM-131 on gastric emptying and upper gastrointestinal (GI) symptoms in patients with type 1 diabetes and previously documented DGE. METHODS: In a double-blind cross-over study, 10 patients with type 1 diabetes (age, 45.7 ± 4.4 y; body mass index, 24.1 ± 1.1 kg/m(2)) and previously documented DGE were assigned in random order to receive a single dose of RM-131 (100 µg, subcutaneously) or placebo. Thirty minutes later, they ate a radiolabeled solid-liquid meal containing EggBeaters (ConAgra Foods, Omaha, NE), and then underwent 4 hours of gastric emptying and 6 hours of colonic filling analyses by scintigraphy. Upper GI symptoms were assessed using a daily diary, gastroparesis cardinal symptom index (total GCSI-DD) and a combination of nausea, vomiting, fullness, and pain (NVFP) scores (each rated on a 0-5 scale). RESULTS: At screening, participants' mean level of hemoglobin A1c was 9.1% ± 0.5%; their total GCSI-DD score was 1.66 ± 0.38 (median, 1.71), and their total NVFP score was 1.73 ± 0.39 (median, 1.9). The t1/2 of solid gastric emptying was 84.9 ± 31.6 minutes when subjects were given RM-131 and 118.7 ± 26.7 when they were given a placebo. The median difference (Δ)was 33.9 minutes (interquartile range [IQR] -12, -49), or -54.7% (IQR, -21%,-110%). RM-131 decreased gastric retention of solids at 1 hour (P = .005) and 2 hours (P = .019). Numeric differences in t1/2 for gastric emptying of liquids, solid gastric emptying lag time, and colonic filling at 6 hours were not significant. Total GCSI-DD scores were 0.79 on placebo (IQR, 0.75, 2.08) and 0.17 on RM-131 (IQR, 0.00, 0.67; P = .026); NVFP scores were lower on RM-131 (P = .041). There were no significant adverse effects. CONCLUSIONS: RM-131 significantly accelerates gastric emptying of solids and reduces upper GI symptoms in patients with type 1 diabetes and documented DGE.

A Systematic Review of the Long-Term Clinical Success of Gastric Peroral Endoscopic Myotomy for Refractory Gastroparesis.

Gastroparesis is a chronic and debilitating gastrointestinal disorder with few medical treatment options. Traditional surgical management has involved laparoscopic pyloromyotomy or gastric stimulation. In recent years, gastric peroral endoscopic myotomy (GPOEM) has become an attractive, less invasive option for patients with refractory gastroparesis. There is little information on the long-term clinical success of GPOEM in patients with refractory gastroparesis. This systematic review aims to evaluate the data on this procedure's long-term clinical efficacy and safety. A comprehensive literature review was done in PubMed, EMBASE, Ovid, and Google Scholar databases from the date of earliest entry in May 2017 up to August 15, 2022. The Gastroparesis Cardinal Symptom Index (GCSI) score, adverse reaction, and length of stay were analyzed. Eleven studies were eligible for inclusion (900 patients), seven of the studies were retrospective, while four were prospective. The GCSI is a 6-point Likert scale questionnaire that assesses improvement in gastroparesis. An average decrease of GCSI by 1 point compared to baseline GCSI for all patients (described as clinical success) was found in 662 patients out of 713 (92.8%) at one-year follow-up, 421 out of 460 (91.5%) at two-year follow-up, 270 out of 270 (100%) at three-year follow-up, and 102 out of 102 (100%) at four-year follow-up. Adverse events occurred in 62 out of 835 patients (in nine studies), with two of the most frequent being bleeding and mucosal tears. GPOEM is an effective and safe treatment option for patients with refractory gastroparesis, with symptom improvement noted up to four years postoperatively.

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.

Gastroparesis-Related Symptoms in Patients With Type 2 Diabetes Mellitus: Early Detection, Risk Factors, and Prevalence.

Background The symptoms of gastroparesis, such as bloating, postprandial fullness, early satiety, nausea, and abdominal discomfort, progressively worsen the quality of life of the affected individuals. The diagnosis is established on the assessment of gastric function that confirms delayed gastric emptying in the absence of structural etiologies. This study aimed to detect gastroparesis-related clinical symptoms early in patients with type 2 diabetes mellitus (T2DM), investigate the concomitant risk factors, and evaluate the prevalence. Methodology This study was conducted at the Department of Medicine and Diabetes Outdoor Clinic of Sheikh Zayed Hospital, Rahim Yar Khan from February 13, 2022, to February 11, 2023. The study involved 175 patients with T2DM who reported gastroparesis-related symptoms. The demographic and clinical characteristics, symptom severity, complications, related risk factors, duration of disease, medications, body mass index (BMI), fasting plasma glucose, and glycated hemoglobin (HbA1C) levels were assessed. The severity of diabetic gastroparesis was established using the disease-specific Patient Assessment of Gastrointestinal Disorders-Symptom Severity Index (PAGI-SYM) and the Gastroparesis Cardinal Symptom Index (GCSI). The five-point scale of the PAGI-SYM and the four-degree severity scores of GCSI were assessed. Neuropathy disability scores and motor evacuation functions were analyzed. Data were analyzed from these questionnaires, special proforma, and patient interviews. Results The clinical features of diabetic gastroparesis were observed in 44% of T2DM patients with mild-grade gastroparesis in 38 (21.7%), moderate in 30 (17.1%), and severe-grade gastroparesis-related symptoms in nine (5.2%) patients. The main manifestations were early satiety (45.1%), stomach fullness (44.5%), bloating (38.3%), and nausea (33.1%). Diabetic gastroparesis symptoms were considerably linked to disease duration of more than 10 years (p = 0.02), high HbA1c (p = 0.001), increased fasting blood glucose (p = 0.003), polyneuropathy, cigarette smoking, and history of comorbid conditions (p = 0.009). Obesity and the female gender were the forecasters of the manifestation of at least one cardinal gastroparesis symptom. Conclusions Gastric emptying is significant in the pathogenesis of gastroparesis-related symptoms. Disease duration of more than 10 years, poor glycemic control with hyperglycemia, high HbA1C, polyneuropathy, and cigarette smoking must be considered as predictors for early detection and risk factors for the advancement of gastroparesis in T2DM. Gastroparesis-related common symptoms of early satiety, bloating, and stomach fullness were considerably linked to the additional risk factors of hypercholesteremia, chronic microvascular complications, concomitant cardiovascular diseases, and a positive family history of diabetes mellitus. There was no relationship between BMI, age, types of treatment, and the degree of gastroparesis severity. The prevalence and severity of gastroparesis symptoms were particularly high among obese females with poor glycemic control and longer disease duration.

Efficacy of Pro-Kinetic Agents in Type 2 Diabetes Mellitus Patients With Gastroparesis Using Lactulose Hydrogen Breath Testing: A Randomized Trial.

Aim The aim of the study was to determine the efficacy of prokinetic agents in diabetic gastroparesis patients. Method This was a randomized open-label trial conducted on 50 patients with type 2 diabetes experiencing diabetic gastroparesis, which was diagnosed with the lactulose hydrogen breath test. After randomization, all 50 patients were divided into four arms (cinitapride, metoclopramide, levosulpiride, and domperidone) of different prokinetics and followed up for four weeks; after which, repeat gastroparesis cardinal symptom index score and orocecal transit time were recorded in order to assess the response to the treatment. Result There was no statistically significant difference among the four groups in terms of all the baseline characteristics except for gender (p=0.032). The follow-up gastroparesis cardinal symptom index was collected for 50 patients but repeat orocecal transit time could be performed only in 37 patients. In all four groups, there was a statistically significant (p<0.05) improvement in terms of orocecal transit time and gastroparesis cardinal symptom index scores. But there was no statistically significant difference in relative efficacy amongst these study groups. Conclusion Our study showed statistically significant improvement with four prokinetics drugs in terms of gastroparesis cardinal symptom index score and orocecal transit time, but there was no statistically significant benefit of one prokinetic drug over the other. Our study showed promising results with regard to prokinetic use in diabetic gastroparesis.

The Short-Term Effects and Tolerability of Low-Viscosity Soluble Fibre on Gastroparesis Patients: A Pilot Clinical Intervention Study.

Gastroparesis is a motility disorder that causes severe gastric symptoms and delayed gastric emptying, where the majority of sufferers are females (80%), with 29% of sufferers also diagnosed with Type-1 or Type-2 diabetes. Current clinical recommendations involve stringent dietary restriction and includes the avoidance and minimization of dietary fibre. Dietary fibre lowers the glycaemic index of food, reduces inflammation and provides laxation. Lack of dietary fibre in the diet can affect long-term gastrointestinal health. Our previously published rheological study demonstrated that "low-viscosity" soluble fibres could be a potentially tolerable source of fibre for the gastroparetic population. A randomised controlled crossover pilot clinical study was designed to compare Partially-hydrolysed guar gum or PHGG (test fibre 1), gum Arabic (test fibre 2), psyllium husk (positive control) and water (negative control) in mild-to-moderate symptomatic gastroparesis patients (requiring no enteral tube feeding). The principal aim of the study was to determine the short-term physiological effects and tolerability of the test fibres. In n = 10 female participants, post-prandial blood glucose, gastroparesis symptoms, and breath test measurements were recorded. Normalized clinical data revealed that test fibres PHGG and gum Arabic were able to regulate blood glucose comparable to psyllium husk, while causing far fewer symptoms, equivalent to negative control. The test fibres did not greatly delay mouth-to-caecum transit, though more data is needed. The study data looks promising, and a longer-term study investigating these test fibres is being planned.

Symptom variability throughout the day in patients with gastroparesis.

BACKGROUND: Symptoms of gastroparesis (Gp) can fluctuate at different times of the day. Our aims are (1) To characterize Gp symptom variability throughout the day and in relation to meals and (2) to compare the daily symptom variability in subtypes of Gp-diabetic gastroparesis (DGp) and idiopathic gastroparesis (IGp). METHODS: Patients with Gp filled Patient Assessment of Gastrointestinal Symptoms (PAGI-SYM) and completed a modified GCSI-DD seven times a day (GCSI-Throughout the Day [GCSI-TTD]; before and after meals, and before going to bed) over a 2-week period. KEY RESULTS: A total of 44 patients participated (86% females), including 29 (66%) with IGp, 13 (30%) with DGp, and 2 (4%) with postsurgical Gp. Using the GCSI-TTD, patients with Gp reported significant postprandial worsening of overall symptom severity, as well as severities of nausea, early satiety, stomach fullness, and abdominal pain. Patients also had progressive worsening of the overall symptom severity, early satiety, stomach fullness, and abdominal pain during the day; however, nausea severity did not differ during the day. Number of vomiting and retching episodes did not show significant variations postprandially or during the day. Patients with IGp had greater symptom severity throughout the day and greater postprandial increase in symptoms compared to patients with DGp. CONCLUSIONS AND INFERENCES: Patients with Gp experience postprandial worsening of overall symptom severity, as well as severities of nausea, early satiety, stomach fullness, and abdominal pain. These symptoms also progressively worsen during the day, except for the severity of nausea which persists throughout the day. Understanding the symptom variability in patients with Gp throughout the day and postprandially may be useful in treatment of patients with Gp.

Therapeutic response to domperidone in gastroparesis: A prospective study using the GCSI-daily diary.

Common symptoms of gastroparesis include nausea, vomiting, early satiety, postprandial fullness, and upper abdominal pain. Domperidone is used for treatment of gastroparesis. Daily symptom scoring may help document efficacy. AIM: To determine the effectiveness of domperidone for gastroparesis symptoms using the gastroparesis cardinal symptom index-daily diary (GCSI-DD) and to determine which symptoms improve and when with domperidone treatment. METHODS: Symptomatic patients with diabetic or idiopathic gastroparesis were enrolled. Gastric emptying was performed using 4 hour scintigraphy. GCSI-DD recorded symptoms at baseline and during six weeks of treatment with domperidone 10 mg TID. GCSI-DD records severity of nausea, early satiety, postprandial fullness, upper abdominal pain, overall gastroparesis symptoms on a scale of 0 (no symptom) to 4 (very severe) and records the number of vomiting episodes per day. RESULTS: Thirty-four patients with gastroparesis (5 diabetic, 29 idiopathic) participated in this open label study. Treatment duration averaged 36.9 ± 7.6 days. Improvement in overall gastroparesis symptoms occurred on day 3 of treatment and maintained during the treatment. Early satiety, postprandial fullness, and overall symptom severity significantly improved from baseline to the final week of treatment (P < .05 for all), whereas nausea had borderline improvement (P = .055). Side effects included palpitations (5 patients), headache (5), breast tenderness (2), menstrual bleeding (2), dizziness (1), drowsiness (1), chest pain (1), swelling (1), constipation (1). CONCLUSIONS: Domperidone improves symptoms of gastroparesis, reducing overall gastroparesis symptom severity and decreasing early satiety, postprandial fullness, and nausea. GCSI-DD is useful to document efficacy of therapy for gastroparesis.