Gastric Emptying Time Research Articles

A long-term follow-up study of gastric peroral endoscopic myotomy (G-POEM) in a large cohort of patients with postsurgical gastroparesis.

Postoperative gastroparesis occurs after surgeries which affect the upper digestive tract. Gastric peroral endoscopic myotomy (G-POEM) is a treatment for postoperative gastroparesis. The present study boasts the long-term efficacy and safety of G-POEM in a large cohort of patients. Gastroparesis Cardinal Symptom Index (GCSI) and Gastroesophageal Reflux Disease Questionnaire (GERDQ) were utilized for the assessment of postsurgical gastroparesis symptoms. Gastroscope was used to observe the anastomotic site. Three-dimensional ultrasound was used to measure the morphological structure of the gastric antrum and pylorus tube. Gastric emptying time was calculated by analyzing the volume change of gastric antrum. Significant clinical effectiveness of G-POEM was observed. The GCSI score, including each subscale score, showed significant decrease after G-POEM. Before G-POEM, there was a negative correlation between GCSI score and the inner diameter of pylorus, as well as a positive correlation with the length of pyloric tube. The similar results were found in the scores of nausea/vomiting and postprandial fullness/early satiety subscales. No correlation was observed between GCSI score and the emptying time, nor between the emptying time and the parameters of antrum morphology. After G-POEM, no correlation was found between GCSI (including subscales) score, the emptying time, and the parameters of antrum morphology. Patients who exhibited as clinical non-responders often accompanied with GERD symptoms. After G-POEM, the score of GERDQ decreased significantly. Either before or after G-POEM, no correlation was noticed between GERDQ scores, the emptying time and the parameters of antrum morphology. The technique of G-POEM was demonstrated as a minimally invasive approach with the long-term efficacy and safety in therapying postoperative gastroparesis.

Neck triangle nerve enlargement in hereditary transthyretin amyloidosis correlates with changes in the autonomic, cardiac, and gastrointestinal systems.

Hereditary transthyretin amyloidosis (ATTRv) is a hereditary disease that affects multiple bodily systems. Although sonography generally reveals enlargement of nerves in the limbs, the brachial plexus, and vagus nerve, the clinical significance of these findings remains unclear. We performed sonographic measurements of the median nerve, cervical spinal nerves at the C5-C7 level, and the vagus nerve in patients with ATTRv and healthy controls. Clinical profiles and cardiac and gastrointestinal examination results were also collected for linear regression analysis. We recruited 47 patients with ATTRv (males/females: 34/13, age: 65.6±5.3 years). The sampled segments were all significantly larger than those of the controls. In the clinical profiles, the sum of the Z scores of the neck triangle nerves (cervical spinal nerves and vagus nerve) and of all nerves (cervical spinal nerves, vagus nerve, and median nerve at the wrist) significantly correlated with the familial amyloid polyneuropathy stage, onset of autonomic nervous system (ANS) symptoms, and autonomic symptom scores. On cardiac examinations, several ultrasonography and magnetic resonance imaging parameters (primarily those that reflect heart volume) were found to be significantly correlated with the sum of the Z scores of the cervical spinal nerves but not with the Z score of the vagus nerve. In gastrointestinal evaluation, the cross-sectional area of the vagus nerve was correlated with gastric emptying time parameters on scintigraphy. Neck triangle nerve enlargement on sonography correlated with parameters related to ANS dysfunction, indicating that nerve enlargement observed on ultrasonography may serve as a potential surrogate biomarker of ATTRv.

Impact of the stepwise implementation of INFOGEST semi-dynamic conditions on in vitro starch and protein digestion: A case study on lentil cotyledon cells

The impact of food design parameters on digestion is mostly studied using static in vitro digestion models. In this work, the complexity of the static model was gradually increased, by implementing several dynamic gastric reactor conditions, i.e., gradual (i) acidification, (ii) pepsin addition, and (iii) emptying, as well as (iv) saliva in the oral phase. As a relevant case study, starch and protein digestion was studied in lentil cotyledon cells under these conditions. Implementation of these dynamic parameters affected gastric proteolysis, linked to the pH-dependence of pepsin, and amylolysis, linked to the pH-dependence of salivary amylase activity. Though gastrointestinal hydrolysis kinetics were affected by the applied simulation conditions, similar levels of starch and protein digestion were generally reached at the end of the simulated digestion. Salivary amylase was not completely inactivated at the low gastric pH conditions, resulting in significantly higher levels of small intestinal starch digestion upon saliva inclusion. Gastric emptying significantly affected macronutrient hydrolysis kinetics. In that regard, an approach separately considering gastric samples taken upon different gastric emptying times should be preferred over the pooling of gastric samples before simulating small intestinal digestion.

Gastrointestinal Dysmotility, Autonomic Function and Small Intestinal Bacterial Overgrowth Among People with Well-Controlled HIV.

Gastrointestinal dysfunction, including microbiome changes and increased translocation across a compromised gastrointestinal barrier plays a role in the chronic inflammation experienced by people with HIV (PWH). It is unknown whether autonomic neuropathy (AN) may contribute to these mechanisms by altering gastrointestinal motility. This is a cross-sectional study of 100 PWH and 89 controls. All participants underwent assessment of gastrointestinal transit times using a wireless motility capsule (WMC). All PWH and a subset of controls also underwent: a standardized battery of autonomic function tests summarized as the Modified Composite Autonomic Severity Score (MCASS) and its adrenergic, cardiovagal and sudomotor sub-scores, breath testing for small intestinal bacterial overgrowth (SIBO), and the Patient Assessment of Upper Gastrointestinal Disorders Symptoms (PAGI-SYM) and Composite Autonomic Symptom Score 31 (COMPASS-31) questionnaires. PWH displayed shorter gastric emptying times (GET) and longer small bowel and colonic transit times (SBTT, CTT) compared to controls. Among PWH, GET was associated with PAGI-SYM score. The MCASS and its sudomotor sub-score (reflecting peripheral sympathetic function) were associated with SBTT but not GET or CTT. PWH with prolonged SBTT (>6h) were more likely to have SIBO. Gastrointestinal motility is altered in PWH. This study provides preliminary evidence that changes in autonomic function may influence SBTT in PWH and that prolonged SBTT may contribute to the development of SIBO. Future studies are needed to more fully elucidate the pathophysiologic links between HIV-associated AN, altered gastrointestinal motility, the gastrointestinal microbiome, chronic inflammation, and resulting morbidity and mortality among PWH.

Development of Sinomenine Hydrochloride Sustained-release Pellet With Multiple Release Characteristics.

Due to the gastrointestinal side effects, the clinical application of sinomenine hydrochloride (SH) in rheumatoid arthritis is limited. The elderly population constitutes the primary group affected by this disease, and within this demographic, there are significant variations in gastric emptying time. To reduce the influence of individual differences on drug efficacy and concurrently alleviate gastrointestinal side effects, the SH sustained-release pellets with multiple release characteristics were developed, which comprised both regular sustained-release pellets and enteric-coated sustained-release pellets. The drug-loaded layer formulation was optimized by full factorial design. With the optimal formulation, the drug-loaded pellets achieved a yield of 96.05%, an encapsulation efficiency of 83.36% for SH, a relative standard deviation of 3.26% in SH content distribution, an average roundness of 0.971 for the pellets, and the particle size span of 0.808. The pellets with a 4h SH release profile in an acidic environment and pellets displaying 4h acid resistance followed by an 8h SH release behavior in the intestinal environment were individually prepared through in vitro dissolution tests. The results demonstrated stable and compliant dissolution behavior of the formulation, along with excellent stability and physical appearance. This research offers novel insights and references for the innovative formulation of SH.

Intragastric botulinum toxin injection directly regulates ghrelin expression via reactive oxygen species and NF-κB signaling

AimsOne effective clinical strategy to combat obesity is intragastric botulinum toxin (BTX) injection, which increases gastric emptying time and regulates appetite. However, it remains unknown if and how BTX affects ghrelin levels. Materials and methodsAn obese animal model was established by feeding male mice with high-fat diet (HFD). BTX was administered by subserosal injection in the antrum via an upper midline laparotomy. The mice were monitored in terms of body weight and blood biochemical parameters. Glucose utility and insulin sensitivity were measured by intraperitoneal glucose and insulin tolerance tests. Additionally, stomach and liver were histologically examined after BTX treatment. AGS gastric adenocarcinoma cells were used to investigate the molecular mechanism by which BTX affects ghrelin expression. Key findingsIn HFD-fed mice, BTX injection significantly decreased both food intake and body weight over a 3-week monitoring period. Moreover, HFD-induced hyperglycemia, hyperinsulinemia, dyslipidemia and obesity readouts were improved after BTX injection. Importantly, mice also exhibited decreased plasma and gastric ghrelin levels after BTX injection. In cultured AGS cells, BTX significantly increased reactive oxygen species (ROS) levels and activated nuclear factor-κB (NF-κB), which led to decreased ghrelin expression. Pre-treatment with inhibitors of either ROS or NF-κB reversed the effects of BTX on ghrelin expression in the cultured cells. SignificanceBTX decreases ghrelin expression in HFD-fed animals and in AGS cells through an ROS/NF-κB-dependent pathway. This mechanism may contribute to decreased food intake in obese subjects receiving intragastric BTX injection for weight control.

Structural changes and in vitro bioaccessibility of CPP-febisgly complexes: Dependence on iron load

The effect of casein phosphopeptides (CPP) and ferrous bisglycinate (FebisGly) at different ratios (1:20, 1:10, and 1:5 w/w) on iron supplementation was investigated. The in vitro bioaccessibility, structural changes, antioxidant activity, and the effect of absorption inhibitors were also explored. The results demonstrated that CPP enhanced the bioaccessibility of FebisGly by 68.72 % ± 0.18 % and increased the β-sheet content from 21.60 % ± 0.23 % to 67.92 % ± 0.12 %, forming a stable secondary structure. The particle size distribution (PSD) and rheological analyses indicated that CPP significantly contributed to the formation of chelated irons, resulting in a uniform PSD and enhanced viscoelasticity. Moreover, it prolonged the gastric emptying time, reducing gastric irritation further. The carboxyl and amino groups in the CPP molecules participated in chelation reaction, improved the antioxidant activity, and competed with phytic acid, tannic acid, and cellulose for iron. Overall, these results laid a foundation for developing novel iron supplementation strategies.

Predicting Response to Neuromodulators or Prokinetics in Patients With Suspected Gastroparesis Using Machine Learning: The "BMI, Infectious Prodrome, Delayed GES, and No Diabetes" Model.

Pharmacologic therapies for symptoms of gastroparesis (GP) 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 GP-like symptoms. Subjects with suspected GP underwent simultaneous gastric emptying scintigraphy (GES) and wireless motility capsule and were followed for 6 months. Subjects were included if they were started on neuromodulators and/or prokinetics. Subjects were considered responders if their GP Cardinal Symptom Index 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. 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 nonresponders. A ridge regression model with the variables, such as body mass index, infectious prodrome, delayed gastric emptying scintigraphy, no diabetes, 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 gastric emptying time, duodenal motility index, no diabetes, and functional dyspepsia performed better (AUC-ROC of 0.75). 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 GP-like symptoms.

Intraoperative pyloric drainage is unnecessary during esophagectomies: a meta-analysis and systematic review of randomized controlled trials.

Objective: The topic of this meta-analysis is the comparison of gastric conduit esophageal reconstructions with or without pyloroplasty. Background: Surgical procedures, especially minimal invasive esophagectomy (MIE) can be a curative treatment in the early stages of esophageal cancer. Previously, intraoperative pyloroplasty was routinely performed, but nowadays it became debated again in the light of minimally invasive esophagectomy. Methods: A comprehensive search was performed in multiple databases to identify randomized controlled trials investigating the topic. Two independent authors performed the selection based on predefined criteria. Statistical analysis was performed to assess any significant difference, then the bias and quality of the data were estimated. Results: Nine relevant RCTs consisting of 529 patients with esophageal cancer were identified. No significance was found in mortality [odds ratio (OR): 0.85; p = 0.642], anastomosis leakage (OR: 0.57; p = 0.254), respiratory morbidity (OR: 0.51; p = 0.214) and vomiting (OR: 0.74; p = 0.520), however the results about gastric emptying time (GET) were controversial (weighted mean difference (WMD): -67.71; p = 0.009, OR: 2.75; p = 0.072). Significant heterogeneity was not detected except for GET. Trial sequential analyses (TSA) show that a certain conclusion would require more data except in the binary variables of GET. Conclusion: We conclude that the pyloric drainage procedure is not routinely necessary, but further well-designed studies would be needed, especially in Europe.

Comparison of Gas-sensing Capsule With Wireless Motility Capsule in Motility Disorder Patients.

Motility disorders are prevalent, often leading to disrupted regional or whole gut transit times. In this study, we conducted a comparative analysis between the wireless motility capsule and an innovative gas-sensing capsule to evaluate regional and whole gut transit times in individuals with diagnosed motility disorders. We prospectively enrolled 48 patients (34 women) diagnosed with functional dyspepsia and/or functional constipation according to Rome IV criteria. Patients ingested the capsules in tandem. We assessed the agreement between transit times recorded by both devices using Spearman correlation and Bland-Altman analysis. Additionally, diagnostic concordance between the capsules were evaluated using confusion matrices. We observed a significant correlation between the wireless motility capsule and the gas-sensing capsule for gastric emptying time (r = 0.79, P < 0.001) and colonic transit time (r = 0.66, P < 0.001). The gas-sensing capsule exhibited a sensitivity of 0.83, specificity of 0.96, and accuracy of 0.94 when using the standard cutoff for delayed gastric emptying (5 hours). Similarly, when applying the cutoff value for delayed colonic transit (> 59 hours), the gas-sensing capsule demonstrated a sensitivity of 0.79, specificity of 0.84, and accuracy of 0.82. Importantly, the gas-sensing capsule was well-tolerated, and no serious adverse events were reported during the study. Our findings underscore the gas-sensing capsule's suitability as a dependable tool for assessing regional and whole gut transit times. It represents a promising alternative to the wireless motility capsule for evaluating patients with suspected motility disorders.

An Overview of Floating Drug Delivery System

The goal of Floating Drug Delivery Systems (FDDS) is to arrange the current emphasis on the basic flotation mechanism to attain stomach retention time. The most current advancements in FDDS are thoroughly discussed, including the formulation and physiological factors influencing stomach retention, methods for designing floating systems, and the characteristics of their classification and formulation. Since dosage forms stay in the stomach longer than conventional dosage forms, the capacity to extend and control the gastric emptying time is a major asset. Gastric emptying of dosage forms is a highly variable process. Drugs with gastroretentive systems have a much longer residence time in the stomach area, improving bioavailability, decreasing drug waste, and increasing solubility for medications that are less soluble in high pH environments. These benefits are achieved over a period of many hours. This review provides a brief overview of floating medication delivery devices

The effects of bit chewing on gastric emptying and orocecal transit times in clinically normal horses

The effects of bit chewing on gastric emptying and orocecal transit times in clinically normal horses

Pharmacokinetic and Safety Evaluation of MBZM-N-IBT, A Lead Against Chikungunya Virus

Chikungunya virus (CHIKV) infection was previously found to be inhibited by MBZM-N-IBT both in vitro and in vivo. To further assess its suitability for in vivo application, toxicity and pharmacokinetics were investigated. It showed no acute toxicity orally with an estimated LD50 of more than 5000 mg/kg in rats. While it showed toxicity at 1000 mg/kg in the chronic toxicity study, it was better tolerated at 500 mg/kg by rats. At 50 mg/kg, it was found to be safe in a 9-month study. A pharmacokinetic study revealed Tmax less than the gastric emptying time. High plasma protein binding supported its higher elimination half-life. In silico analysis predicted 22 metabolites. The majority of these metabolites fall in OECD class 5 and support the low toxicity of MBZM-N-IBT.

Short-term Outcomes of Pancreatoduodenectomy in Patients with Liver Cirrhosis: A Systematic Review and Meta-analysis.

The objective of this study was to compare short-term outcomes of pancreatoduodenectomy between patients with and without liver cirrhosis (LC). It is not uncommon to encounter a patient with LC and with an indication for pancreatoduodenectomy; however, the knowledge on the outcomes after pancreatoduodenectomy in patients with LC is poorly developed. A systematic review and meta-analysis was conducted in line with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement standards. Short-term outcomes of pancreatoduodenectomy between patients with and without LC were compared using random effects modeling and the certainty of the evidence was assessed using the GRADE system. Analysis of 18,184 patients from 11 studies suggested LC increased the risk of postoperative mortality (odds ratio [OR]: 3.94, P < 0.00001), major complications (OR: 2.25, P = 0.0002), and pancreatic fistula (OR: 1.73, P = 0.03); it resulted in more blood loss (mean difference [MD]: 204.74 ml, P = 0.0003) and longer hospital stay (MD: 2.05 days, P < 0.00001). LC did not affect delayed gastric emptying (OR: 1.33, P = 0.21), postoperative bleeding (OR: 1.28, P = 0.42), and operative time (MD: 3.47 minutes, P = 0.51). Among the patients with LC, Child-Pugh B or C class increased blood loss (MD: 293.33 ml, P < 0.00001), and portal hypertension increased postoperative mortality (OR: 2.41, P = 0.01); the other outcomes were not affected. Robust evidence with high certainty suggests LC of any severity with or without portal hypertension results in at least a fourfold increase in mortality and a twofold increase in morbidity after pancreatoduodenectomy. Whether such risks increase with the severity of the liver disease or decrease with optimization of underlying liver disease should be the focus of future research.

Millets have the potential to increase satiety and reduce the feeling of hunger: a systematic review

A systematic review was conducted to understand the satiety value of millets and their ability to lessen the feeling of hunger. Only six eligible studies had the relevant information for this analysis. These studies compared millet-based foods with refined rice, potatoes, wheat, oats, and rye and found that millets have the potential to lower the hunger index. The proposed mechanism suggests that millets’ richness in fiber is responsible for increasing gastric volume and prolonging gastric emptying time. Millet-based food stays longer in the stomach, thereby prolonging the feeling of satiety or fullness. Fiber also helps to slow down the release of glucose into the blood. Furthermore, the protein in millets increases insulin sensitivity, which also reduces the glucose response. This proposed mechanism, which increases satiety and delays the glucose response, is responsible for lowering the blood lipid profile and promoting weight loss.

DOMPERIDONE VS METOCLOPRAMIDE: COMPARATIVE EVALUATION OF EFFICACY IN TREATING DIABETIC GASTROPARESIS

Diabetic gastroparesis, a common complication of diabetes mellitus, presents a challenging clinical scenario characterised by delayed gastric emptying and symptoms such as nausea, vomiting, abdominal pain, and bloating. Objectives: The primary aim of the study is to compare domperidone vs metoclopramide to evaluate their efficacy in treating diabetic gastroparesis. Methods: This comparative study was conducted in DHQ Hospital Nowshera Khyber Pakhtunkhwa—from June 2022 to June 2023. Data was collected from 190 patients from both genders. Patients meeting the inclusion criteria are randomised into Group A (Domperidone) and Group B (Metoclopramide). The severity of gastroparesis symptoms is assessed using validated symptom-scoring tools before treatment initiation and at regular intervals throughout the study. Results: Data was collected from 190 patients suffering from DM. The mean age of the patients in group A was 52.4 ± 8.2 years and in group B, 53.1 ± 7.5 years. There were 105 female and 185 male patients. The mean duration of DM is 12.3 ± 4.1 years and 11.8 ± 3.8 years in groups A and B, respectively. Group A (Domperidone) and Group B (Metoclopramide) demonstrated significant improvement in symptom scores from baseline to the final assessment. Group A exhibited a substantial reduction in symptom score from 18.2 ± 4.5 at baseline to 8.7 ± 3.2 at the end of the study (p &lt; 0.001), while Group B showed a decrease from 17.9 ± 4.3 to 9.5 ± 3.8 (p &lt; 0.001). Moreover, both groups experienced notable reductions in gastric emptying time. Conclusion: It is concluded that both domperidone and metoclopramide are effective in managing diabetic gastroparesis, with nuances in their safety profiles.

Evaluation of Gastric Emptying Time in Patients with Subclinical Hypothyroidism and Euthyroid Goiter

Evaluation of Gastric Emptying Time in Patients with Subclinical Hypothyroidism and Euthyroid Goiter

Gastric antral web presenting with esophageal stricture and severe malnutrition

Gastric antral web is a rare cause of gastric outlet obstruction in children. Common complaints include intermittent non-bilious vomiting, bloating, pain, loss of appetite, and weight loss. Herein, we report a case of gastric antral web presenting with esophageal stricture and malnutrition, which was followed for many years with a misdiagnosis. An 8-year-old African boy was referred to our pediatric gastroenterology clinic due to recurrent vomiting and severe malnutrition. According to his medical history, the patient began experiencing non-bilious vomiting at 40 days of age and a diagnosis of gastroesophageal reflux was made. He was hospitalized multiple times and received nasogastric tube feedings in the following 4 years. He was re-evaluated for growth retardation and malnutrition at 4 years of age. He had been diagnosed with gluten enteropathy and was fed a gluten-free diet. Recently, he developed difficulty swallowing solid food and was only able to consume liquid meals. Esophagography revealed segmental stenosis in the distal portion of the esophagus. After stricture excision with thoracotomy, upper gastrointestinal series with a radiopaque substance indicated normal esophageal passage; however, prolonged gastric emptying time was also noted. Upon examination during laparotomy, a congenital web was detected in the antral region and was excised. Esophageal and gastric pathologies were consistent with stricture caused by reflux esophagitis and gastric antral web. Today, gastric antral web is mostly diagnosed and treated in infancy. Near total obstruction is relatively easy to diagnose; however, many patients with partial obstruction are followed-up for years with an incorrect diagnosis. Therefore, it should be considered in such cases, persistent vomiting and gastroesophageal reflux may be associated with esophageal stricture.

Formulation and Evaluation of Microspheres Containing Mefenamic Acid by Inotropic Gelation Method

Drugs with a narrow absorption window in the gastrointestinal tract (GIT) will have poor absorption. For these drugs, gastro retentive drug delivery system offers the advantage in prolonging the gastric emptying time. Losartan potassium is prescribed to treat hypertension. The current study was projected to prepare a Losartan potassium gastro retentive drug delivery system (GRDDS) of floating tablets was planned to enhance the gastric residence time, thus prolong the drug release. Losartan potassium effervescent floating tablets were prepared by utilizing the direct impression method, using polymers such as HPMCk15, xanthan gum, microcrystalline cellulose, and Sodium carbonate, with lubricants such as magnesium stearate and talc. In the present study, sodium bicarbonate was incorporated as a gas generating agent. And combination of sodium bicarbonate and citric acid was found to achieve optimum in vitro buoyancy. Total eight formulations were designed and evaluated for pre-compression parameters known as angle of repose, bulk density, tapped density, Hausner's ratio, compressibility index, and post -compression parameters are uniformity of weight variation, hardness, thickness, friability, floating lag time, and in vitro dissolution investigation and FTIR along with DSC is carried out

Transcutaneous vagal nerve stimulation for treating gastrointestinal symptoms in individuals with diabetes: a randomised, double-blind, sham-controlled, multicentre trial

Aims/hypothesisDiabetic gastroenteropathy frequently causes debilitating gastrointestinal symptoms. Previous uncontrolled studies have shown that transcutaneous vagal nerve stimulation (tVNS) may improve gastrointestinal symptoms. To investigate the effect of cervical tVNS in individuals with diabetes suffering from autonomic neuropathy and gastrointestinal symptoms, we conducted a randomised, sham-controlled, double-blind (participants and investigators were blinded to the allocated treatment) study.MethodsThis study included adults (aged 20–86) with type 1 or 2 diabetes, gastrointestinal symptoms and autonomic neuropathy recruited from three Steno Diabetes Centres in Denmark. Participants were randomly allocated 1:1 to receive active or sham stimulation. Active cervical tVNS or sham stimulation was self-administered over two successive study periods: 1 week of four daily stimulations and 8 weeks of two daily stimulations. The primary outcome measures were gastrointestinal symptom changes as measured using the gastroparesis cardinal symptom index (GCSI) and the gastrointestinal symptom rating scale (GSRS). Secondary outcomes included gastrointestinal transit times and cardiovascular autonomic function.ResultsSixty-eight participants were randomised to the active group, while 77 were randomised to the sham group. Sixty-three in the active and 68 in the sham group remained for analysis in study period 1, while 62 in each group were analysed in study period 2. In study period 1, active and sham tVNS resulted in similar symptom reductions (GCSI: −0.26 ± 0.64 vs −0.17 ± 0.62, p=0.44; GSRS: −0.35 ± 0.62 vs −0.32 ± 0.59, p=0.77; mean ± SD). In study period 2, active stimulation also caused a mean symptom decrease that was comparable to that observed after sham stimulation (GCSI: −0.47 ± 0.78 vs −0.33 ± 0.75, p=0.34; GSRS: −0.46 ± 0.90 vs −0.35 ± 0.79, p=0.50). Gastric emptying time was increased in the active group compared with sham (23 min vs −19 min, p=0.04). Segmental intestinal transit times and cardiovascular autonomic measurements did not differ between treatment groups (all p>0.05). The tVNS was well-tolerated.Conclusions/interpretationCervical tVNS, compared with sham stimulation, does not improve gastrointestinal symptoms among individuals with diabetes and autonomic neuropathy.Trial registrationClinicalTrials.gov NCT04143269FundingThe study was funded by the Novo Nordisk Foundation (grant number NNF180C0052045)Graphical