Richard W. McCallum

Gastric Electrical Stimulation Improves Outcomes of Patients With Gastroparesis for up to 10 Years

BACKGROUND & AIMSnWe assessed the long-term clinical outcomes of gastric electrical stimulation (GES) therapy with Enterra (Enterra Therapy System; Medtronic, Minneapolis, MN) in a large cohort of patients with severe gastroparesis.nnnMETHODSnGastroparesis patients (n=221; 142 diabetic, 48 idiopathic, and 31 postsurgical) treated with Enterra (Medtronic) for 1-11 years were retrospectively assessed; 188 had follow-up visits and data were collected for at least 1 year (mean 56 months, range 12-131 months). Total symptom scores (TSSs), gastric emptying, nutritional status, weight, hospitalizations, use of prokinetic and/or antiemetic medications, levels of HbA1c levels (in diabetic patients), and adverse events were evaluated at the beginning of the study (baseline) and during the follow-up period.nnnRESULTSnTSS, hospitalization days, and use of medications were significantly reduced among all patients (P<.05). More patients with diabetic (58%) and postsurgical gastroparesis (53%) had a greater than 50% reduction in TSS than those with idiopathic disease (48%; P=.32). Weight significantly increased among all groups, and 89% of J-tubes could be removed. At end of the follow-up period, all etiological groups had similar, abnormal delays in mean gastric retention. Thirteen patients (7%) had their devices removed because of infection at the pulse generator site.nnnCONCLUSIONSnGES therapy significantly improved subjective and objective parameters in patients with severe gastroparesis; efficacy was sustained for up to 10 years and was accompanied by good safety and tolerance profiles. Patients with diabetic or postsurgical gastroparesis benefited more than those with idiopathic disease.

Clinical-histological associations in gastroparesis: results from the Gastroparesis Clinical Research Consortium: Clinical-histological associations in gastroparesis

Backgroundu2002 Cellular changes associated with diabetic (DG) and idiopathic gastroparesis (IG) have recently been described from patients enrolled in the Gastroparesis Clinical Research Consortium. The association of these cellular changes with gastroparesis symptoms and gastric emptying is unknown. The aim of this study was to relate cellular changes to symptoms and gastric emptying in patients with gastroparesis.

Dietary Intake and Nutritional Deficiencies in Patients With Diabetic or Idiopathic Gastroparesis

BACKGROUND & AIMSnGastroparesis can lead to food aversion, poor oral intake, and subsequent malnutrition. We characterized dietary intake and nutritional deficiencies in patients with diabetic and idiopathic gastroparesis.nnnMETHODSnPatients with gastroparesis on oral intake (N = 305) were enrolled in the National Institute of Diabetes and Digestive and Kidney Diseases Gastroparesis Registry and completed diet questionnaires at 7 centers. Medical history, gastroparesis symptoms, answers to the Block Food Frequency Questionnaire, and gastric emptying scintigraphy results were analyzed.nnnRESULTSnCaloric intake averaged 1168 ± 801 kcal/day, amounting to 58% ± 39% of daily total energy requirements (TER). A total of 194 patients (64%) reported caloric-deficient diets, defined as <60% of estimated TER. Only 5 patients (2%) followed a diet suggested for patients with gastroparesis. Deficiencies were present in several vitamins and minerals; patients with idiopathic disorders were more likely to have diets with estimated deficiencies in vitamins A, B(6), C, K, iron, potassium, and zinc than diabetic patients. Only one-third of patients were taking multivitamin supplements. More severe symptoms (bloating and constipation) were characteristic of patients who reported an energy-deficient diet. Overall, 32% of patients had nutritional consultation after the onset of gastroparesis; consultation was more likely among patients with longer duration of symptoms and more hospitalizations and patients with diabetes. Multivariable logistic regression analysis indicated that nutritional consultation increased the chances that daily TER were met (odds ratio, 1.51; P = .08).nnnCONCLUSIONSnMany patients with gastroparesis have diets deficient in calories, vitamins, and minerals. Nutritional consultation is obtained infrequently but is suggested for dietary therapy and to address nutritional deficiencies.

A phase 2a, randomized, double‐blind 28‐day study of TZP‐102 a ghrelin receptor agonist for diabetic gastroparesis

Backgroundu2002 Gastroparesis causes significant morbidity and treatment options are limited. TZP‐102 a novel, macrocyclic, selective, oral ghrelin receptor agonist, was evaluated in a randomized, double‐blind, placebo‐controlled trial in patients with diabetic gastroparesis.

Phase 2b, randomized, double-blind 12-week studies of TZP-102, a ghrelin receptor agonist for diabetic gastroparesis.

TZP‐102, a potent, oral, ghrelin receptor agonist, improved diabetic gastroparesis symptoms in Phase 2a.

Spectrum of gastric emptying patterns in adult patients with cyclic vomiting syndrome.

Backgroundu2002 Cyclic vomiting syndrome (CVS) in adults is a disorder characterized by recurrent and stereotypic episodes of severe nausea, vomiting and abdominal pain separated by symptom‐free intervals. Both rapid and delayed gastric emptying (GE) have been observed but the reports involved small numbers of CVS patients.

Effects of octreotide and erythromycin on gastric myoelectrical and motor activities in patients with gastroparesis.

Simultaneous recordings of gastric manometry andmyoelectrical activity were made in 10 patients withgastroparesis. Intravenous erythromycin (100 mg) wasadministered in the fasting state for a period of 30 min. Subcutaneous injection of octreotide(100 μg) was administered before one of the fouridentical test meals. It was found that octreotidesignificantly decreased the antral motility index(30-min fasting: 4.51 ± 1.04 vs 1.75 ±0.97, P < 0.02; 60-min fed: 5.16 ± 1.44 vs 3.4± 1.41, P < 0.05) and the dominant power ofthe EGG (fasting power: 35.19 ± 1.54 vs 30.84± 1.57 dB, P < 0.004; postprandial powerincrease: 5.52 ± 1.06 vs 0.27 ± 0.87, P< 0.001). Erythromycin significantly increased theantral motility index (3.16 ± 0.96 vs 9.5± 0.61, P < 0.001) and the dominant power ofthe EGG (28.86 ± 1.57 dB vs 33.55 ± 1.59dB, P < 0.005) in the fasting state. An improvement in theregularity of the gastric slow wave was also noted witherythromycin. It was concluded that: (1) the inhibitoryeffect of octreotide on postprandial gastric motility and myoelectrical activity suggests thatcaution should be exercised when octreotide is used inpatients with gastroparesis; and (2) the stimulatoryeffect of erythromycin on gastric myoelectrical activity may enhance gastric motility and gastricemptying in patients with gastroparesis.

Relamorelin Reduces Vomiting Frequency and Severity and Accelerates Gastric Emptying in Adults With Diabetic Gastroparesis

BACKGROUND & AIMSnGastroparesis is an important complication of diabetes. We investigated the effects of relamorelin (a pentapeptide-selective agonist of the ghrelin receptor that speeds gastric emptying in patients with diabetes) in patients with diabetic gastroparesis.nnnMETHODSnWe performed a double-blind trial of 204 patients (78% Caucasian; 67% female; mean age, 55 y; 88% with type 2 diabetes) with diabetic gastroparesis with moderate to severe symptoms and delayed gastric emptying at 27 clinical centers, from June 2012 until August 2013. Patients were assigned randomly (1:1:1) to groups given placebo or subcutaneous relamorelin 10 μg once or twice daily. The primary end point was the half-time of gastric emptying. Secondary end points included nausea, abdominal pain, bloating, early satiety, as well as the composite score of these 4 subjective symptoms and vomiting frequency and severity.nnnRESULTSnTwice-daily relamorelin significantly accelerated gastric emptying (P < .03) and reduced vomiting frequency (by ∼60%) and severity vs placebo (P ≤ .033). Compared with placebo, relamorelin did not improve other gastrointestinal symptoms, such as abdominal pain and satiety. In the 119 patients (58.3%) with baseline vomiting, twice-daily relamorelin significantly reduced the half-time of gastric emptying and vomiting, as well as nausea, abdominal pain, bloating, and early satiety compared with placebo (composite score, Pxa0= .043). No overall safety concerns were identified.nnnCONCLUSIONSnIn a clinical trial of patients with diabetic gastroparesis, relamorelin (10 μg twice daily) significantly accelerated gastric emptying and significantly reduced vomiting, compared with placebo. Among patients with baseline vomiting, relamorelin had prokinetic effects and significantly reduced vomiting and also improved other symptoms of diabetic gastroparesis compared with placebo. ClincialTrials.gov number: NCT01571297.

Outcomes and Factors Associated With Reduced Symptoms in Patients With Gastroparesis

BACKGROUND & AIMSnGastroparesis is a chronic clinical syndrome characterized by delayed gastric emptying. However, little is known about patient outcomes or factors associated with reduction of symptoms.nnnMETHODSnWe studied adult patients with gastroparesis (of diabetic or idiopathic type) enrolled in the National Institute of Diabetes and Digestive and Kidney Diseases Gastroparesis Clinical Research Consortium Gastroparesis Registry, seen every 16 weeks and treated according to the standard of care with prescribed medications or other therapies at 7 tertiary care centers. Characteristics associated with reduced symptoms, based on a decrease of 1 or more in the gastroparesis cardinal symptom index (GCSI) score after 48 weeks of care, were determined from logistic regression models. Data were collected from patients for up to 4 years (median, 2.1 y).nnnRESULTSnOf 262 patients, 28% had reductions in GCSI scores of 1 or more at 48 weeks. However, there were no significant reductions in GCSI score from weeks 48 through 192. Factors independently associated with reduced symptoms at 48 weeks included male sex, age 50 years and older, initial infectious prodrome, antidepressant use, and 4-hour gastric retention greater than 20%. Factors associated with no reduction in symptoms included overweight or obesity, a history of smoking, use of pain modulators, moderate to severe abdominal pain, a severe gastroesophageal reflex, and moderate to severe depression.nnnCONCLUSIONSnOver a median follow-up period of 2.1 years, 28% of patients treated for gastroparesis at centers of expertise had reductions in GCSI scores of 1 or greater, regardless of diabetes. These findings indicate the chronic nature of gastroparesis. We identified factors associated with reduced symptoms that might be used to guide treatment. ClinicalTrials.gov no: NCT00398801.

The addition of pyloroplasty as a new surgical approach to enhance effectiveness of gastric electrical stimulation therapy in patients with gastroparesis

Backgroundu2002 Improvement of gastroparesis (GP) symptoms has been documented in patients treated with gastric electrical stimulation (GES), but acceleration of gastric emptying (GET) is unpredictable. The aim of our study was to evaluate the advantage of adding surgical pyloroplasty (PP) to GES for improvement of GET and control of symptoms in diabetes mellitus (DM), idiopathic (ID), and postvagotomy (P‐V) GP.