Recent advances from the Gastroparesis Clinical Research Consortium: toward better understanding, diagnosis, and treatment

After food is swallowed, muscles in the stomach wall grind it into smaller pieces and push it into the small intestine to continue digestion. In people with gastroparesis, however, these muscles work poorly—or not at all—and the stomach takes too long to empty its contents. This slower movement is called “delayed gastric emptying,” and it can cause chronic nausea, vomiting, and abdominal pain, often leading to malnutrition, dehydration, and other serious complications. People with gastroparesis typically need to adhere to strict, low-portion diets that are low in fat and fiber, and at times they may need to avoid solid foods altogether.

Developing treatments for gastroparesis has been challenging, largely because the underlying causes are unclear. For unknown reasons, women are significantly more likely to develop the disorder than men. Diabetes, surgery, and other conditions are known to cause gastroparesis in some people, but idiopathic gastroparesis—in which the cause is not identified—is more common. In 2006, the NIDDK established the Gastroparesis Clinical Research Consortium to accelerate research on the causes and progression of this disorder and to explore new approaches for treatment. The Consortium is made up of several clinical research centers across the country, allowing researchers to share techniques and tools and, importantly, to assemble the Consortium’s most valuable resource: a broad spectrum of hundreds of people with gastroparesis who volunteered to be a part of the Gastroparesis Registry. The Registry is the largest clinical and physiologic data repository for gastroparesis in the world, containing a large body of information accessible to qualified researchers, such as detailed test results, samples, and questionnaires. Women make up the majority of participants, reflecting the higher incidence of gastroparesis in this group. The information collected in the Registry is used by researchers to link symptoms, severity, and treatment responses to patient characteristics—a critical step toward understanding the causes, progression, and outcomes of the disorder. Consortium scientists can also access the Registry when recruiting people for clinical trials, which could benefit Registry participants who are eager to try new therapies. Over the years, the Consortium has undertaken several such trials to test treatments for gastroparesis. This Gastroparesis Registry includes only adult participants, but the Consortium recently built upon its success to establish the first national pediatric registry (the Pediatric Gastroparesis Registry, or PGpR) for children and adolescents with gastroparesis. Enrollments for both registries are ongoing.

Recent studies from the Consortium have leveraged information from the adult Registry to help improve diagnosis of gastroparesis, which can be challenging because many of its symptoms are not specific to the disorder and could be mistakenly attributed to something else, like indigestion. Consortium researchers are trying to help with diagnosis by identifying groups of people who are at higher risk. For example, the Consortium recently studied people in the Registry who have both diabetes and symptoms of gastroparesis, and they found that those with delayed gastric emptying had a higher number of diabetic complications than those who showed normal gastric emptying. Retinopathy (damage to blood vessels in the eye) was particularly associated with delayed gastric emptying, which suggests that people with diabetic retinopathy are also more likely to have gastroparesis. However, gastroparesis can occur in people who do not have complications of diabetes.

Consortium researchers are also using information from the Registry to investigate the underlying causes of gastroparesis, including why the stomach is not working properly. One possibility is that there could be defects in the activity of the nerves that envelope the stomach and control its muscles. Specifically, the researchers wanted to know whether the sympathetic and parasympathetic parts of the nervous system, which both control involuntary actions such as heart rate and stomach muscle activity, could be important in gastroparesis. While both sympathetic and parasympathetic systems are always active at some level, they exist in balance: the sympathetic component is more active during periods of stress, slowing the stomach’s activity, while the parasympathetic system counters the sympathetic system and is more active during rest. The researchers found that this delicate balance is disrupted in many people with gastroparesis, with the parasympathetic system less able to offset the effects of the sympathetic responses, even when the body is at rest. Studies such as this, which identify the key mechanisms underlying gastroparesis, could identify potential new avenues for treatment.

Other recent studies from the Consortium focused on symptom management. For example, one study found that approximately 12 percent of people with gastroparesis participating in the Registry acknowledged that they used cannabis for symptom relief. Registry participants who were experiencing severe nausea and abdominal pain were more likely to use cannabis and likely to report that it helps ease their symptoms. Research on cannabis for various health conditions is in its early stages, but these results should raise health care providers’ awareness that people with gastroparesis may be using cannabis to manage their symptoms, and that U.S. Food and Drug Administration (FDA)-approved synthetic products related to cannabis might be effective therapeutic agents. In fact, a portion of Registry participants were using at least one of these approved products, and they too were likely to report that it helps them manage their symptoms. The Consortium also sought to determine whether a procedure called gastric electrical stimulation (GES) is effective for treating symptoms of gastroparesis. GES involves implanting an electronic device in the abdomen to deliver mild electrical impulses to the stomach’s nerves and muscles. The device has been controversial because evidence on its effectiveness has been slow to accumulate, primarily because the procedure is expensive and requires additional visits and maintenance, making clinical trials difficult. Again using information from the Registry, researchers gathered information on people who underwent GES and determined that the procedure was effective for treating nausea in the participants with more severe gastroparesis. However, larger clinical trials would be necessary to test its efficacy more fully and to identify which people with gastroparesis would most likely benefit from this procedure.

These studies are only a recent sampling of research endeavors from the Consortium. Future years will see the Consortium continuing to undertake clinical studies to further understand, diagnose, and treat gastroparesis. The disorder can be devastating, but this research gives strong hope that the lives of people coping with gastroparesis will continue to improve.