Treatment of type 2 diabetes using meal-triggered gastric electrical stimulation.

BACKGROUND: The TANTALUS System (MetaCure Limited) is a minimally invasive implantable device for the treatment of type 2 diabetes. The system detects food intake by sensing gastric electrical variations and applies electrical stimulation to the gut synchronized to natural gastric activity. The system is commercially available in Europe and Israel and is in clinical trials in the United States. It has been tested in 132 patients worldwide to date. OBJECTIVES: To re-analyze previously reported datafrom different studies. This retrospective analysis of the type 2 diabetes subpopulation analyzed the expected benefit and characterized the significance of baseline A1c in the determination of the expected clinical outcome. METHODS: From the total cohort of 132 patients implanted with the TANTALUS device in 10 different centers in Europe and the U.S., we identified 50 subjects (27 females, 23 males) who were obese with uncontrolled T2DM on a stable regime of oral medication for 3 months prior to implant. This population had similar inclusion/exclusion criteria as well as treatment protocols and were all treated for at least 24 weeks. The analysis was based on the A1c change compared to baseline. RESULTS: Data after 24 weeks demonstrated a reduction in A1c in 80% of the patients with average drop in A1c of 1.1 +/- 0.1%. The average weight loss was 5.5 +/- 0.7 kg. CONCLUSIONS: The results suggest that the TANTALUS stimulation regime can improve glucose levels and induce moderate weight loss in obese T2DM patients.

Electrical stimulation of the gut for the treatment of type 2 diabetes: the role of automatic eating detection.

BACKGROUND: Automatic eating detection (AED) can potentially support treatments that need to be synchronized with food intake. This article analyzes an implantable AED device working in conjunction with gastric stimulation intended to treat type 2 diabetes (T2DM). The device continuously senses for changes in tissue impedance and electrical activity induced by food intake and initiates treatment sessions upon detection. This article reviews AED performance as well as its relevance to treatment outcomes. METHODS: Obese T2DM (n = 12) were implanted with gastric leads and the TANTALUS device. An AED algorithm was embedded in the device and was used to initiate periods of electrical stimulation during food intake. AED performance was assessed using patients' food diaries. The treatment outcome at 37 weeks postimplants was correlated with the rates of stimulation during large meals vs stimulation during periods of no caloric intake. RESULTS: The algorithm was able to detect 73% of meals consumed while sensing. The rate of false stimulations was 28%. Stimulation during meals was significantly correlated (R(2) = 0.45, p < 0.05) with hemoglobin A1c change (average drop in hemoglobin A1c was -1 +/- 0.4%) but not with changes in body weight (average drop -4.7 +/- 2.8 kg). Stimulation during periods with no caloric intake was negatively correlated with hemoglobin A1c reduction (R(2) = 0.27, p < 0.05). CONCLUSIONS: Sensing of gastric activity can be used for detection of food intake. The synchronization of gastric stimulation to periods of food intake is correlated with metabolic outcomes. AED may also benefit other applications such as drug delivery and control of food restriction devices.

Association between gastric electromechanical activity and satiation in dogs.

OBJECTIVE: The objective of this study was to validate the use of impedance for measurement of antral contractions and to determine the relationship between food-induced changes in gastric motility and satiation. RESEARCH METHODS AND PROCEDURES: In Experiment 1, three dogs were implanted with an antral strain gauge and bipolar electrodes for measurement of local tissue impedance. Impedance and strain gauge recordings were obtained simultaneously during antral contractions to correlate impedance changes with contractile events. In Experiment 2, seven dogs were implanted with two pairs of gastric electrodes for simultaneous recording of slow wave activity and impedance. The changes in the rate of slow waves and of antral contractions assessed by impedance during food intake were characterized. RESULTS: Variations in strain gauge amplitude were highly correlated with changes in antral impedance (R2: 0.70 to 0.82, p < 0.05). In Experiment 2, slow wave rate was significantly reduced after food intake and reached a nadir at satiation (5.0 +/- 0.3 vs. 3.8 +/- 0.5 events/min, p < 0.001). Likewise, the amplitude of antral contractions assessed by variations in impedance was significantly increased after food intake, peaking at satiation (5.3 +/- 1.4 vs. 12.2 +/- 4.3 Ohms, p < 0.01). DISCUSSION: Measurement of impedance is a reliable tool for assessing gastric contractility. Food ingestion significantly reduces slow wave rate and enhances antral contractions. Peak changes in these two variables occur at the time of satiation. Electrical measurements of both slow waves and impedance may be used to estimate gastric motility and satiation.

One-year experience with Tantalus: a new surgical approach to treat morbid obesity.

BACKGROUND: Increased caloric density in modern processed foods may be an important factor underlying the prevalence of obesity, because low-volume, high-caloric food intake may delay activation of volume-dependent gastric mechanical activity known to induce the feeling of fullness. We therefore hypothesized that enhancement of gastric contractions by electrical stimulation at an early stage of the meal will reduce food intake and body weight in morbidly obese subjects. METHODS: The study was a prospective, non-randomized, open-label, single-center trial. 12 subjects (age 36.1 +/- 2.8 years, BMI 43.2 +/- 2.7 kg/m(2), weight 128.8 +/- 5.2 kg, means+/-SEM) underwent laparoscopic implantation with the Tantalus system. A pulse generator with 3 bipolar leads was implanted: 2 pairs in the antrum and a 3rd pair in the fundus. The system was activated at week 6. All subjects were followed for 20 weeks and 9 of them for 52 weeks. RESULTS: All subjects finished the initial 20-week observation period. Following activation of the Tantalus System, a reduction (P<0.05) in hunger and an increase in cognitive control (P<0.05) as assessed by the Three-Factor Eating Questionnaire (TFEQ) could be observed. Body weight decreased (P<0.05) from 128.8+/-5.2 to 119.9+5.9 (17.6+4.3% EWL, N=12) after 20 weeks (14 weeks of treatment). In the 9 subjects continuing for 52 weeks (46 weeks of treatment), body weight further decreased to 112.4 +/- 3.8 kg (26.6 +/- 8.5 %EWL, N=9). Blood pressure decreased (P<0.05) from 142 +/- 6.1/91 +/- 3.2 to 125.5 +/- 4.0/83 +/- 2.6 mmHg by week 20 and 128.8 +/- 3.8 / 86.3 +/- 3.6 mmHg after 1 year. The frequency and severity of device and/or procedure-related adverse events indicate that the method is safe and well-tolerated. CONCLUSION: This data suggests that gastric stimulation by the minimally invasive Tantalus System is safe and leads to favorable changes in eating behavior, clinically significant weight loss and reduction in blood pressure. Treatment with the Tantalus System is therefore a promising minimally invasive treatment for obesity.

Enhancement of antral contractions and vagal afferent signaling with synchronized electrical stimulation.

Gastric filling activates vagal afferents involved in peripheral signaling to the central nervous system (CNS) for food intake. It is not known whether these afferents linearly encode increasing contractions of the antrum during antral distension (AD). The aim of this study was to investigate effects of AD and electrically enhanced antral contractions on responses of vagal afferents innervating the antrum. Single-fiber recordings were made from the vagal afferents in anesthetized male Long-Evans rats. Antral contractions were measured with a solid-state probe placed in the antrum. A nonexcitatory electrical stimulation (NES) inducing no smooth muscle contractions was applied during the ascending phase of antral contractions to enhance subsequent antral contractions. Fifty-six fibers identified during AD (1 ml for 30 s) were studied through different types of mechanical stimuli. Under normal conditions, one group of fibers exhibited rhythmic firing in phase with antral contractions. Another group of fibers had nonrhythmic spontaneous firing. Responses of 15 fibers were tested with NES during multiple-step distension (MSD). NES produced a mean increase in antral contraction amplitude (177.1 +/- 35.3%) and vagal afferent firing (21.6 +/- 2.6%). Results show that both passive distension and enhanced antral contractions activate distension-sensitive vagal afferents. Responses of these fibers increase linearly to enhanced antral contraction induced by NES or MSD up to a distending volume of 0.6 ml. However, responses reached a plateau at a distending volume >0.8 ml. We concluded that enhanced contraction of the antrum can activate vagal afferents signaling to the CNS.