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Clinical Gastroenterology and... Apr 2024Prokinetics have limited effectiveness for treating symptoms of gastroparesis. Thus, alternative or adjunct therapies, such as gastroparesis diets or neuromodulators,... (Clinical Trial)
Clinical Trial
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.).
Topics: Humans; Diet; Gastric Emptying; Gastroparesis; Nausea; Neurotransmitter Agents; Treatment Outcome; Vomiting
PubMed: 37913936
DOI: 10.1016/j.cgh.2023.10.014 -
Drug Design, Development and Therapy 2023Dipeptidyl peptidase IV (DPP-IV) is an enzyme responsible for the degradation of the incretin hormone glucagon-like peptide-1 (GLP-1). DPP-IV plays a significant role in... (Review)
Review
Dipeptidyl peptidase IV (DPP-IV) is an enzyme responsible for the degradation of the incretin hormone glucagon-like peptide-1 (GLP-1). DPP-IV plays a significant role in regulating blood glucose levels by modulating the activity of GLP-1. In the context of diabetes, DPP-IV inhibitors effectively block the activity of DPP-IV, hence mitigating the degradation of GLP-1. This, in turn, leads to an extension of GLP-1's duration of action, prolongs gastric emptying, enhances insulin sensitivity, and ultimately results in the reduction of blood glucose levels. Nonetheless, reported adverse events of DPP-IV inhibitors on T2DM patients make it essential to understand the activity and mechanism of these drugs, particularly viewed from the perspective of finding the effective and safe add-on medicinal plants, to be implemented in clinical practice. This review is intended to bring forth a thorough overview of plants that work by reducing DPP-IV activity, from computational technique, enzymatic study, animal experiments, and studies in humans. The articles were searched on PubMed using "Plants", "DPP-IV", "DPP-IV inhibitor", "GLP-1", "Type 2 diabetes", "diabetes", "in silico", "in vitro", "in vivo", "studies in human", "clinical study" as the query words, and filtered for ten years of publication period. Eighteen plants showed inhibition against DPP-IV as proven by in silico, in vitro, and in vivo studies; however, only ten plants were reported for efficacy in clinical studies. Several plant-based DPP-IV inhibitors, eg, , and , have established their functional role in inhibiting DPP-IV and have proven their effectiveness through studies in humans earning them a prominent place in therapeutic discovery.
Topics: Animals; Humans; Dipeptidyl-Peptidase IV Inhibitors; Dipeptidyl Peptidase 4; Blood Glucose; Plants, Medicinal; Hypoglycemic Agents; Diabetes Mellitus, Type 2; Glucagon-Like Peptide 1
PubMed: 38024536
DOI: 10.2147/DDDT.S426870 -
Journal of Clinical Gastroenterology Oct 2023Gastroparesis is commonly attributed to idiopathic or diabetic causes.
BACKGROUND
Gastroparesis is commonly attributed to idiopathic or diabetic causes.
GOALS
We aimed to describe atypical causes of gastroparesis and examine the clinical features and severity of delayed gastric emptying compared with idiopathic and diabetic causes.
STUDY
Between 2018 and 2021, gastroparesis patients being evaluated at our tertiary care center completed a 4-hour gastric emptying scintigraphy and questionnaires assessing for gastrointestinal disorders, including patient assessment of upper gastrointestinal symptoms. Patients were divided into groups relating to gastroparesis cause: diabetic, postsurgical (PSGp), connective tissue (CTGp), neurological and idiopathic.
RESULTS
Two hundred fifty-six patients with delayed emptying on gastric emptying scintigraphy completed the questionnaires. Gastroparesis causes included 149 (58.2%) idiopathic, 60 (23.4%) diabetic, 29 (11.3%) postsurgical, 13 (5.1%) connective tissue, and 5 (2.0%) neurological. In each group, most patients were female and White. Gastric retention at 4 hours was significantly greater in patients with diabetic (39.3±25.7% P <0.001), postsurgical (41.3±24.0% P =0.002), and connective tissue gastroparesis (37.8±20.0% P =0.049) compared with patients with idiopathic gastroparesis (25.5±17.6%). In PSGp, diabetic and idiopathic causes, the main symptoms were early satiety and postprandial fullness, whereas in CTGp, bloating and abdominal distension were the predominant symptoms. Vomiting severity was significantly greater in patients with diabetes compared with idiopathic gastroparesis (2.9±1.9 vs. 2.1±1.8 P =0.006).
CONCLUSIONS
Atypical causes contributed to gastroparesis in 47 of 256 (18.4%) patients with delayed gastric emptying. Gastric emptying was significantly more delayed in PSGp and CTGp patients. PSGp patients mainly experienced stomach fullness and early satiety, whereas CTGp patients had predominantly bloating and distension.
Topics: Humans; Female; Male; Gastroparesis; Prevalence; Gastric Emptying; Vomiting; Surveys and Questionnaires
PubMed: 36730846
DOI: 10.1097/MCG.0000000000001786 -
Journal of Clinical Medicine Dec 2023Esophagectomy is a technically complex operation performed for both benign and malignant esophageal disease. Medical and surgical advancements have led to improved... (Review)
Review
Esophagectomy is a technically complex operation performed for both benign and malignant esophageal disease. Medical and surgical advancements have led to improved outcomes in esophagectomy patients over the past several decades; however, surgeons must remain vigilant as complications happen often and can be severe. Post-esophagectomy complications can be grouped into early and late categories. The aim of this review is to discuss the early complications of esophagectomy along with their risk factors, work-up, and management strategies with special attention given to anastomotic leaks.
PubMed: 38137691
DOI: 10.3390/jcm12247622 -
Journal of Clinical GastroenterologyProkinetics and proton pump inhibitors are first-line drugs for functional dyspepsia (FD) patients. However, no available treatment is effective for most FD patients,...
BACKGROUND AND AIMS
Prokinetics and proton pump inhibitors are first-line drugs for functional dyspepsia (FD) patients. However, no available treatment is effective for most FD patients, and the pathogenesis is still unclear. The purpose of this study was to investigate the therapeutic effect of transcutaneous neuromodulation (TN) on FD and its potential mechanisms.
MATERIALS AND METHODS
Fifty-seven FD patients were enrolled in the study and randomly divided into 3 groups (TN Neiguan (PC6) group, TN Zusanli (ST36) group, and sham TN group) that received corresponding treatment respectively for 4 weeks. Then, all the patients enrolled received TN PC6 combined with ST36 treatment for another 4 weeks. Dyspepsia symptom questionnaire, Medical outcomes study item short form health survey (SF-36), Hospital Anxiety and Depression Scale were used to assess the severity of symptoms. Gastric accommodation, gastric emptying rate, and related parameters of electrogastrogram were used to assess the pathophysiological mechanism of FD. The possible gastrointestinal hormonal mechanism involved was assessed by detecting serum ghrelin, neuropeptide Y, and vasoactive intestinal peptide. The possible duodenal inflammation mechanism involved was assessed by detecting duodenal mucosa.
RESULTS
TN treatment reduced the dyspepsia symptom score ( P <0.05) and improved the quality of life. After TN treatment, the gastric accommodation ( P <0.01), the gastric emptying rate ( P <0.01), and the percentages of preprandial ( P <0.05) and postprandial ( P <0.05) gastric slow waves (GSW) were increased. The proportions of preprandial ( P <0.05) and postprandial ( P <0.05) gastric electrical rhythm disorder were reduced. The double acupoint combination therapy further enhanced the therapeutic effect of single acupoint. In addition, the levels of ghrelin ( P <0.001) and neuropeptide Y ( P <0.001) were significantly increased, the level of vasoactive intestinal peptide ( P <0.001) was significantly decreased, and the total number of mast cells ( P <0.001) in the duodenal bulb was significantly decreased after double acupoints combination therapy.
CONCLUSIONS
TN treatment significantly improves the dyspepsia symptoms of FD patients and their quality of life. TN treatment increases the percentage of normal GSW, reduces the proportion of gastric electrical rhythm disorder, and improves the gastric accommodation and gastric emptying rate. The therapeutic effect of TN may be caused by regulating gastrointestinal hormone secretion and alleviating local inflammatory responses in duodenum. In addition, the improvement of TN on GSW was closely related to the decrease of bradygastria.
PubMed: 36226998
DOI: 10.1097/MCG.0000000000001775 -
Neurogastroenterology and Motility Jun 2024Gastroparesis is a motility disorder of the stomach characterized by cardinal symptoms and delayed gastric emptying of solid food in the absence of mechanical... (Review)
Review
BACKGROUND
Gastroparesis is a motility disorder of the stomach characterized by cardinal symptoms and delayed gastric emptying of solid food in the absence of mechanical obstruction. There is significant unmet need in its management, and essentially there are no medications approved for its treatment over four decades.
PURPOSE
The objectives of this review are to develop an understanding of the goals of treatment, the evidence-based criteria for treatment success based on the current scientific understanding of gastroparesis as well as patient response outcomes, and to propose evidence-based principles for the successful development of treatments for gastroparesis. Specifically, we discuss the pathophysiologic targets in gastroparesis, eligibility criteria for clinical trial participation based on validated gastric emptying studies, and the patient response outcome measures that have been validated to appraise effects of treatment on clinically relevant outcomes. These considerations lead to recommendations regarding eligibility, design, and duration of proof-of-efficacy studies, and to endorsing the American Neurogastroenterology and Motility Society Gastroparesis Cardinal Symptom Index Daily Diary as a validated patient response outcome and to justification of the shortening of proof-of-efficacy, placebo-controlled clinical trials to 4 weeks treatment duration after a baseline period. We believe that such approaches will increase the likelihood of successful assessment of efficacy of novel approaches to treating patients with gastroparesis.
PubMed: 38884392
DOI: 10.1111/nmo.14849 -
Expert Opinion on Pharmacotherapy Apr 2024Gastroparesis is a chronic disorder characterized by decreased gastric emptying and presents with nausea, vomiting, and abdominal pain which impacts patients' quality of... (Review)
Review
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.
Topics: Humans; Administration, Intranasal; Dopamine Antagonists; Gastric Emptying; Gastrointestinal Agents; Gastroparesis; Metoclopramide; Quality of Life
PubMed: 38629943
DOI: 10.1080/14656566.2024.2344646 -
Neurogastroenterology and Motility Jan 2024There is limited data on gastric emptying in dyspeptic children. We aimed to determine solid and liquid emptying rates in dyspeptic children and correlate with clinical...
BACKGROUND
There is limited data on gastric emptying in dyspeptic children. We aimed to determine solid and liquid emptying rates in dyspeptic children and correlate with clinical characteristics.
METHODS
Charts of dyspeptic children undergoing 4-hour dual-phase gastric scintigraphy were reviewed for demographics, symptoms, and comorbidities.
KEY RESULTS
In 1078 dyspeptic patients (65% females, median age 13 years) vomiting (55%), nausea (53%), and abdominal pain (52%) were the most common symptoms. The most common comorbidities were mental health (32%), neurologic (27%), and hypermobility spectrum disorders (20%). Solid and liquid emptying rates were aligned in 61.23%. Delayed solid with normal liquid emptying were noted in 2.5%, compared to delayed liquid with normal solid emptying in 26.16%. Abdominal pain had a trend for association with delayed or normal solid emptying (p = 0.06). Nausea was mostly reported with normal solid emptying (p < 0.0001) and underreported in patients <12 years with vomiting (29%). Abnormal solid emptying (rapid and delayed) was noted more frequently in children with mental health disorders (p = 0.027). Rapid liquid emptying was more common in children with genetic disorders (p = 0.032).
CONCLUSION AND INFERENCES
Over half of children with dyspepsia had delayed liquid gastric emptying, and one quarter had delayed liquid with normal solid emptying. Dual-phase gastric emptying studies may help target therapy in dyspeptic children. Nausea is not a reliable symptom for dyspepsia in younger children. Given the significant association of abnormal gastric emptying in children with mental health disorders, we recommend screening and treating children with dyspepsia.
Topics: Female; Humans; Child; Adolescent; Male; Dyspepsia; Gastric Emptying; Vomiting; Abdominal Pain; Nausea
PubMed: 37926966
DOI: 10.1111/nmo.14701 -
American Journal of Physiology.... Apr 2024Multiple studies describe prodromal, nonmotor dysfunctions that affect the quality of life of patients who subsequently develop Parkinson's disease (PD). These prodromal... (Review)
Review
Multiple studies describe prodromal, nonmotor dysfunctions that affect the quality of life of patients who subsequently develop Parkinson's disease (PD). These prodromal dysfunctions comprise a wide array of autonomic issues, including severe gastrointestinal (GI) motility disorders such as dysphagia, delayed gastric emptying, and chronic constipation. Indeed, strong evidence from studies in humans and animal models suggests that the GI tract and its neural, mainly vagal, connection to the central nervous system (CNS) could have a major role in the etiology of PD. In fact, misfolded α-synuclein aggregates that form Lewy bodies and neurites, i.e., the histological hallmarks of PD, are detected in the enteric nervous system (ENS) before clinical diagnosis of PD. The aim of the present review is to provide novel insights into the pathogenesis of GI dysmotility in PD, focusing our attention on functional, neurochemical, and molecular alterations in animal models.
Topics: Animals; Humans; Parkinson Disease; Rodentia; Quality of Life; Gastrointestinal Diseases; Enteric Nervous System
PubMed: 38261717
DOI: 10.1152/ajpgi.00225.2023 -
The Journal of Pharmacy and Pharmacology Dec 2023This study aimed to evaluate the effects of prucalopride, a prokinetic agent that acts as a potent serotonin agonist of 5-HT4 receptors, on gastric emptying and small...
OBJECTIVES
This study aimed to evaluate the effects of prucalopride, a prokinetic agent that acts as a potent serotonin agonist of 5-HT4 receptors, on gastric emptying and small bowel transit and assess its impact on the absorption of metronidazole.
METHODS
Six healthy volunteers, three men and three women, aged between 20 and 27 years, with a body weight ranging from 50 to 80 kg, were enrolled in this study. The pharmacokinetics and gastrointestinal transit parameters were evaluated simultaneously through pharmacomagnetography assessment, combining alternating current biosusceptometry and blood analysis.
KEY FINDINGS
The results showed that prucalopride enhances gastric emptying and small bowel transit when administered orally and significantly impacts the rate of metronidazole absorption, leading to enhanced bioavailability and rapid therapeutic response.
CONCLUSION
Pharmacomagnetography assessment allows simultaneous tracking of transit by images and is a valuable method for analysing drug absorption using multiple instruments.
Topics: Male; Humans; Female; Young Adult; Adult; Metronidazole; Gastric Emptying; Gastrointestinal Transit
PubMed: 37831664
DOI: 10.1093/jpp/rgad088