Defining the Effect of Gastric Electrical Stimulation on Serum Insulin Levels in Human Subjects

Up to thirty-two adult patients with gastroparesis who have undergone implantation of a gastric stimulation device at least three months prior are candidates for study. Diabetic patients who are taking exogenous insulin are excluded from study The study consists of two groups, an EXPERIMENTAL group that undergoes turning off the GES and a CONTROL group that does not undergo the turning off of the GES. The subjects are randomized to either the control or experimental group. The study Coordinator will create a block randomization schedule in Excel (Block Randomization in Clinical Trials: Video Tutorial in Microsoft Excel)(10). The study Coordinator will use the Excel randomization schedule to assign the treatment and will administer the stimulus accordingly. No one will be blinded to any of the arms of the study.

After an overnight fast, the patients are placed in the supine position on a hospital bed, and an intravenous line is inserted and capped. The study consists of three separate and consecutive periods: 1. Baseline, a 20-minute period during which GES is left ON at each patient's pre-study settings; 2. Experimental, a 4-hour period during which the GES device is turned OFF; 3. Recovery, a 20-minute period during which GES is turned back ON to the patient's pre-study settings. A 5-ml sample of blood will be removed from each patient after placement of the flexible IV catheter secured with tape, the Baseline, and Recovery study periods. During the Experimental period a blood sample is withdrawn after 30 minutes and then again at the 1-hour, 2-hour, 3-hour and 4-hour intervals through a flexible IV catheter secured with tape , with the possibility of up to 8 blood draws over the duration of the study.

Plasma samples are analyzed for glucose, C-peptide, GLP-1 and insulin levels. The analysis of variance is used to determine whether there is any significant effect of time on the resultant values. In a previous study we examined the variance of patient demographics (age, gender, and BMI). As patients with implanted electrical stimulators typically have different stimulator settings to control their symptoms, this arm of the study examines whether stimulation parameters such as pulse duration, amplitude or frequency have any effect on individual response to gastric electrical stimulation. A correlation coefficient analysis is used to determine if any variable shows a significant effect.

During the study EKG electrodes are placed over the extremities and precordium and recordings continued during the respective Baseline, Experimental, and Recovery periods. EKG signals are digitized and downloaded to a computer for time domain power spectral analysis of heart rate variability using commercially available software. This analysis will determine the influence of sympathetic and parasympathetic mechanisms during the respective time periods.