Studies from the NIH Gastroparesis Clinical Research Consortium: Towards improving our understanding and treatment of gastroparesis

Introduction

The NIH Gastroparesis Clinical Research Consortium (GpCRC) was started in 2005 to improve the understanding of the pathogenesis and natural history of gastroparesis of all etiologies and to advance the diagnosis and therapy of patients affected with this troubling condition. The consortium initially consisted of five centers along with the data coordinating center and the NIH. Over the initial 13 years of study from a number of centers of excellence in gastroparesis, the GpCRC has learned a tremendous amount about gastroparesis as well as conditions with symptoms of gastroparesis but with normal gastric emptying. The areas of study can be divided into five important areas: symptoms, etiologies, pathophysiology, physiologic testing, and treatments. This chapter briefly summaries some of the findings of the Gastroparesis Clinical Research Consortium as published in peer reviewed manuscripts.

Symptoms

The clinical burden of gastroparesis for patients with this disorder is high. Symptoms can be severe and continuous or with variations in severity over time. Different patients may have different types of predominant symptoms, such as nausea/vomiting or early satiety/postprandial fullness. In the GpCRC studies, symptoms of gastroparesis have been quantified using a modified Patient Assessment of Upper Gastrointestinal Disorders Symptoms (PAGI-SYM) questionnaire which assesses symptoms of gastroparesis, dyspepsia, and gastroesophageal reflux disease ; it includes the nine symptoms of the Gastroparesis Cardinal Symptom Index (GCSI) . This modified PAGI-SYM includes additional individual symptom scores for lower abdominal pain, constipation and diarrhea to help assess these lower GI symptoms.

Nausea appears to be the primary symptom as it is present in nearly all patients (95%) . Nausea and vomiting, in particular, are related to the decreased quality of life these patients have. Vomiting is less prevalent than nausea. Vomiting is more prevalent and severe in diabetic gastroparesis than idiopathic gastroparesis. Early satiety and postprandial fullness are also important symptoms . The severity of early satiety and postprandial fullness is associated with body weight, quality of life, and gastric emptying.

Abdominal pain has largely been ignored in gastroparesis; its cause is unknown. Abdominal pain is reported to be the predominant symptom in one-fifth of patients with gastroparesis . Moderate-severe abdominal pain is present in 66% of patients with gastroparesis, impairs quality of life, and is associated with idiopathic etiology and opiate use, but not gastric emptying. Patients with predominant pain have at least as great an impact on disease severity and quality of life as in patients with predominant nausea/vomiting. Increased upper abdominal pain severity was associated with increased severity of each of the nine GCSI symptoms, depression, anxiety, somatization, use of opiate medications, decreased quality of life using the two instruments used by the GpCRC, the generic QOL instrument SF-36 and the more disease specific QOL instrument PAGI-QOL, but not related to severity of delayed gastric emptying or water load ingestion .

Many patients with gastroparesis use opioids for pain control. In the GpCRC registry, 41% of 583 gastroparesis patients were taking opioids . Abdominal pain was the reason for prescription for 61% of patients taking opioids. Mean scores for gastroparesis, nausea/vomiting, bloating/distention, abdominal pain, and constipation scores were higher in opioid users. Opioid use was associated with greater levels of gastric retention, worse quality of life, increased hospitalization, and increased use of antiemetic and pain modulator medications. Thus, in the clinic, opioid use is prevalent among patients with diabetic or idiopathic gastroparesis, and is associated with worse symptoms, delays in gastric emptying, and lower quality of life, as well as greater use of resources. Opiates, although might be helpful for acute traumatic or postsurgical pain, are now not suggested for long term use. In addition, opiates can not only delay gastric emptying, but can cause GI symptoms such as nausea and vomiting. Most treatment trials in gastroparesis limit the use of opiates for study subjects. In the current environment of limiting use of opiates due to their side effects, the number of gastroparesis patients taking opiates will hopefully decrease.

In addition to gastric symptoms, many patients with gastroparesis and the wider population of patients with symptoms of gastroparesis with or without delayed gastric emptying can have symptoms of anxiety and depression . The severity of these symptoms relates to the severity of the gastroparesis symptoms. Psychological dysfunction does not vary by etiology or degree of gastric retention. Although it is likely that the chronic gastric symptoms, which may persist despite treatments, may lead to anxiety and depression, it is interesting to speculate that these central symptoms may themselves be impacting on the gastric-related symptoms. The vagus nerve has bidirectional neural pathways, with efferent motor pathways to the stomach as well as afferent sensory pathways to the CNS. Psychological symptoms should be considered in managing gastroparesis, and often they need to be treated.