Effects of a motilin receptor agonist (ABT-229) on upper gastrointestinal symptoms in type 1 diabetes mellitus: a randomised, double blind, placebo controlled trial.

INTRODUCTION: Erythromycin, a motilin agonist, is a potent prokinetic. ABT-229 is a specific motilin agonist that dose dependently accelerates gastric emptying. Dyspepsia and gastroparesis are common problems in type 1 diabetes mellitus. We aimed to evaluate the efficacy of ABT-229 in symptomatic diabetic patients with and without delayed gastric emptying. METHODS: Patients with type 1 diabetes and postprandial symptoms were randomised (n=270). Based on a validated C(13) octanoic acid breath test, patients were assigned to either the delayed or normal gastric emptying strata. Patients received one of four doses of ABT-229 (1.25, 2.5, 5, or 10 mg twice daily before breakfast and dinner) or placebo for four weeks following a two week baseline. A self report questionnaire measured symptoms on visual analogue scales; the primary outcome was assessment of change in the total upper abdominal symptom severity score (range 0-800 mm) from baseline to the final visit. RESULTS: The treatment arms were similar regarding baseline characteristics. There was symptom improvement on placebo and a similar level of improvement on active therapy for the upper abdominal discomfort severity score (mean change from baseline -169, -101, -155, -143, and -138 mm for placebo, and 1.25, 2.5, 5, and 10 mg ABT-229, respectively, at four weeks by intent to treat). The results were not significantly different in those with and without delayed gastric emptying. The severity of bloating, postprandial nausea, epigastric discomfort, heartburn, and acid regurgitation worsened dose dependently in a greater number of patients receiving ABT-229 than placebo. Overall, 63% of patients on placebo reported a good or excellent global response, and this was not different from the active treatment arms. CONCLUSIONS: The motilin agonist ABT-229 was not efficacious in the relief of postprandial symptoms in diabetes mellitus in the presence or absence of delayed gastric emptying.

A double-blind, randomized, sham-controlled trial of the gastric bubble for obesity.

We investigated the effect of an endoscopically placed gastric balloon, the Garren-Edwards gastric bubble (GEGB), on weight loss in obese patients. Fifty-nine obese patients were entered into a prospective double-blind study and randomized into two groups. In one group (34 patients) the GEGB was inserted, and in the other group (25 patients) a sham insertion was done. All patients participated in a standard weight loss program consisting of dietary therapy, behavior modification, and physical exercise. The bubble was removed endoscopically after 3 months from both groups. Patients were followed for an additional 9 months after bubble removal and weight loss was monitored. Weight loss was the same in both groups at 3 months (18.7 lb vs. 17.2 lb). This was true whether determined by change in pounds, percentage of body weight, or body mass index. We concluded that the GEGB was of no added benefit as compared with sham insertion, when combined with a standard weight loss program. Because of the lack of proven efficacy and the relatively high cost, we recommend that such devices be restricted to controlled studies until significant benefits are proven.

Studies of the prevalence and significance of radiolabeled bile acid malabsorption in a group of patients with idiopathic chronic diarrhea.

We studied radiolabeled fecal bile acid excretion in 11 normal subjects and 17 patients with idiopathic chronic diarrhea for three major purposes: to establish normal values for this test in the presence of increased stool volumes (induced in normal subjects by ingestion of poorly absorbable solutions); to test for bile acid malabsorption in the patients and to correlate this with an independent test of ileal function, the Schilling test; and to compare the results of the bile acid excretion test with the subsequent effect of a bile acid binding agent (cholestyramine) on stool weight. In normal subjects fecal excretion of the radiolabel was increased with increasing stool volumes. As a group, patients with idiopathic chronic diarrhea excreted radiolabeled bile acid more rapidly than normal subjects with induced diarrhea (t1/2 56 +/- 8 vs. 236 +/- 60 h, respectively, p less than 0.005). There was a statistically significant positive correlation between t1/2 of radiolabeled bile acid and Schilling test results in these patients. Although 14 of 17 patients absorbed labeled taurocholic acid less well than any of the normal subjects with comparable volumes of induced diarrhea, cholestyramine had no statistically significant effect on stool weight in the patient group, and in none of the patients was stool weight reduced to within the normal range. In summary, most patients with idiopathic chronic diarrhea have bile acid malabsorption (as measured by fecal excretion of labeled bile acid), but they do not respond to cholestyramine therapy with a significant reduction in stool weight. Although the significance of these findings was not clearly established, the most likely interpretation is that bile acid malabsorption is a manifestation of an underlying intestinal motility or absorptive defect rather than the primary cause of diarrhea.

Percutaneous endoscopic gastrostomy--to push or pull. A prospective randomized trial.

A prospective randomized study was undertaken to evaluate the Ponsky-Gauderer and Sachs-Vine types of gastrostomy kits. The techniques, complications, morbidity, and mortality with each type of device are compared. Both devices are found to compare favorably to the traditional surgically placed gastrostomy.

Preliminary experience with hydrostatic balloon dilation of gastric outlet obstruction.

In treating a group of 15 patients with gastric outlet obstruction, 12 (80%) had good to excellent relief of symptoms. Two patients required surgical intervention. One patient has symptoms that were persistent but mild enough to forego surgery. Balloon dilation offers an alternative to the surgical management of gastric outlet obstruction.