Surgery Section - Gastric Electrical Stimulation

IMPORTANT REMINDER

This Medical Policy has been developed through consideration of medical necessity, generally accepted standards of medical practice, and review of medical literature and government approval status.

Benefit determinations should be based in all cases on the applicable contract language. To the extent there are any conflicts between these guidelines and the contract language, the contract language will control.

The purpose of medical policy is to provide a guide to coverage. Medical Policy is not intended to dictate to providers how to practice medicine. Providers are expected to exercise their medical judgment in providing the most appropriate care.

Description

Gastric electrical stimulation (GES) is performed using an implantable device designed to treat chronic drug-refractory nausea and vomiting secondary to gastroparesis of diabetic or idiopathic etiology. Gastric electrical stimulation is also proposed as a treatment of obesity. The device may also be referred to as a gastric pacemaker.

Currently, there is only one gastric electrical stimulator that has received approval from the U.S. Food and Drug Administration (FDA) (see note below). The EnterraTM Therapy System (formerly named Gastric Electrical Stimulation (GES) System) manufactured by Medtronic is approved for treatment of chronic refractory gastroparesis. No gastric stimulation device is FDA approved for treatment of obesity. The Tantalus® system (MegaCure Ltd) is approved in Europe and there have been two clinical trials in the United States using this device for the treatment of obesity in patients with type 2 diabetes. One study (NCT00547482) using the Tantalus II was terminated and the protocol design is under review. The other study (NCT00276471), a phase I trial with anticipated enrollment of 18 subjects, is currently recruiting patients. The GES system consists of four components:

1. The implanted pulse generator
2. Two unipolar intramuscular stomach leads
3. The stimulator programmer
4. The memory cartridge

With the exception of the intramuscular leads, all other components have been used in other implantable neurological stimulators, such as spinal cord or sacral nerve stimulators. The intramuscular stomach leads are implanted on the greater curvature of the stomach either laparoscopically or during a laparotomy and are connected to the pulse generator that is implanted in a subcutaneous pocket. The programmer sets the stimulation parameters, which are typically set at an on time of 0.1-sec alternating with an off time of 5.0 sec.

Gastroparesis is a chronic disorder of gastric motility characterized by delayed emptying of a solid meal. Symptoms include bloating, distension, nausea, and vomiting. When severe and chronic, gastroparesis can be associated with dehydration, poor nutritional status, and poor glycemic control in diabetics. While most commonly associated with diabetes, gastroparesis is also found in chronic pseudo-obstruction, connective tissue disorders, Parkinson disease, and psychological pathology. Treatment of gastroparesis includes prokinetic agents such as metoclopramide, and antiemetic agents such as metoclopramide, granisetron, or odansetron. Severe cases may require enteral or total parenteral nutrition.

Gastric electrical stimulation has also been investigated as a treatment of obesity as a technique to increase a feeling of satiety with subsequent reduced food intake and weight loss. The exact mechanisms resulting in changes in eating behavior are uncertain but may be related to neuro-hormonal modulation and/or stomach muscle stimulation. There are no gastric electrical stimulation devices approved by the FDA for the treatment of obesity. However, the Transcend® implantable gastric stimulation device, manufactured by Transneuronix Corporation, is currently available in Europe for treatment of obesity. Transneuronix is currently funding clinical trials in the United States and hopes to obtain FDA approval in a couple of years for use of the Transcend® device to promote weight loss in the management of obesity. These clinical trials, (ClinicalTrials.gov Identifier NCT00200083 and NCT00312611) are ongoing, but no longer recruiting participants.

Note: It should be noted that the GES (EnterraTM ) System received FDA approval through a "humanitarian device exemption." This regulatory category was established in 1996 and only applies to devices intended to benefit less than 4,000 patients. The approval process is similar to that of a premarket approval application (PMA), but is exempt from the effectiveness requirements of a PMA. Thus the application is not required to provide results of scientifically valid clinical investigations, but must contain sufficient information for the FDA to determine that the device does not pose unreasonable or significant risk of illness or injury. A humanitarian use device may only be used in facilities that have an Institutional Review Board (IRB) to supervise clinical testing of the device.

Policy/Criteria

1. Gastric electrical stimulation may be considered medically necessary in the treatment of chronic intractable nausea and vomiting secondary to gastroparesis of diabetic or idiopathic etiology when all three of the following criteria are met:
1. Significantly delayed gastric emptying as documented by standard scintigraphic imaging of solid food
2. Patient is refractory or intolerant of two out of three classes of prokinetic medications and two out of three antiemetic medications. (see appendix for classes)
3. Patient's nutritional status is sufficiently low that all of the following criteria for total parenteral nutrition  are met:
   1. Adequate trials of dietary adjustment, oral supplements, or tube enteral nutrition have demonstrated that the patient can receive no more than 30% of his/her caloric needs orally and/or by tube, and
   2. The patient must be in a stage of wasting as indicated by all of the following:
      1. Weight is significantly less than normal body weight for a patient's height and age in comparison with pre-illness weight
      2. Serum albumin is less than 3.4 grams
      3. BUN is less than 10 mg
      4. Phosphorus level is less than 2.5 mg (normal phosphorus is 3-4.5 mg)
2. Gastric electrical stimulation is investigational for all other indications including but not limited to the treatment of obesity.

Scientific Background

Gastric Stimulation for the Treatment of Intractable Nausea and Vomiting Due to Gastroparesis

The data presented to the FDA documenting the "probable benefit" of the GES (EnterraTM) system was based on a multicenter double-blind cross-over study referred to as the WAVESS study (Worldwide Anti-Vomiting Electrical Stimulation Study). (2) The study included 33 patients with intractable idiopathic or diabetic gastroparesis. The primary endpoint of the study was a reduction in vomiting frequency, as measured by patient diaries. In the initial phase of the study, all patients underwent implantation of the stimulator and were randomly and blindly assigned to stimulation ON or stimulation OFF for the first month, with crossover to OFF and ON during the second month. The baseline vomiting frequency was 47 episodes per month, which significantly declined in both ON and OFF groups to 23 and 29 episodes, respectively. However, there were no significant differences in the number of vomiting episodes between the two groups, suggesting a placebo effect.

After the first two months of therapy, patients were asked which month of the cross-over stimulation they preferred; 21 of the 33 patients selected the ON mode as their preferred month, compared to 7 who preferred the OFF mode, and 5 who had no preference. The greater preference for ON stimulation suggests some short-term effect that is not placebo.

In a continuing open phase of the trial, the patients then received the stimulation consistent with their preference. However by 4 months all patients had the device turned ON (it is not clear whether this phase was by preference or design). At 6 and 12 months' follow-up, the mean number of vomiting episodes continued to decline, although only 15 patients were followed for a period of 12 months. Data regarding quality of life were also obtained at 6 and 12 months and showed improvement. At 6 months, there was a significant improvement in 2-hour gastric retention (from 80% retention to 60% retention), but not in 4-hour gastric retention. (Fifty percent gastric retention at 2 hours is considered the upper limits of normal.)

The results of the randomized portion of the study suggest a placebo effect. Therefore, long-term results of gastric electrical stimulation must be validated in a longer term randomized trial. It is interesting to note that the gastric electrical stimulation did not return gastric emptying to normal in the majority of the patients tested. In as much as the device is intended to improve gastric emptying, as a proof of principle it would be interesting to investigate the correlation between the degree of gastric emptying and symptom improvement.

In an update to the WAVESS double-blind study Abell and colleagues report twelve months outcomes for all of the patients. (3) Statistically significant improvements were found for weekly vomiting frequency, total abdominal symptom score, and scintigraphic solid food emptying. At baseline the median vomiting frequency was 17.3 episodes per week with gastroparetic symptoms over a mean 6.2 years. All patients had scintigraphic evidence of delayed gastric emptying at two and four hours, all patients were refractory to prokinetic and antiemetic medications, and fourteen required some form of parenteral or enteral feedings. Results at the end of phase 1 (the blinded phase) showed a 50% decreased vomiting frequency for patients whose devices were in the ON compared to patients whose devices were in the OFF positions (p=0.05). Symptom severity trended toward improvement in the ON versus OFF period, although these changes did not reach statistical significance in phase 1. Before unblinding twenty-one patients expressed preference for the ON position. In a second phase of the study all patients were switched to the ON position with six and twelve months follow-up. Vomiting results at twelve months significantly decreased compared to baseline: 72% for the combined group, 63% for diabetics with gastroparesis and 83% for patients with idiopathic gastroparesis. Total symptom score improved significantly (p<0.05) at six and twelve months. Physical and mental quality of life scores improved significantly compared to baseline (p= less than 0.025). Baseline gastric retention was 78% at two hours. This decreased significantly with electrical stimulation to 65% at six months and 56% at twelve months for the combined group. The changes in two-hour gastric emptying were not significant for the diabetic and idiopathic groups separately. Four-hour gastric emptying improved from 34% retention at baseline to 22% retention at twelve months. The difference was statistically significant for the combined group as well as the diabetic and idiopathic groups separately.

Abel and colleagues published five-year outcomes in a subset of twelve patients from the Gastric Electro-Mechanical Stimulation (GEMS) Study Group. (4) In this subgroup of twelve, baseline total symptom score changed from 37.1 to 15.8 at one to two years and to 20.3 at five years (p<0.005). Weekly vomiting frequency score decreased from 3.9 at baseline to 1.4 at one to two years and 1.7 at five years. Route of nutrition changed also: at five years nine patients were taking oral nutrition representing a 30% change from baseline from enteral or parenteral nutrition to oral foods alone.  Forster and colleagues reported on their experience at a single institution among 55 patients with gastroparesis as documented by gastric retention. (5) While the total symptom score improved, gastric emptying did not change.  Similarly, van der Voort and colleagues reported that seventeen patients with diabetic gastroparesis experienced a decrease in nausea and vomiting and an improvement in glucose control in a prospective case series examining the twelve month outcomes. (6) Lin and colleagues reported significant improvements in upper GI symptoms, health-related quality of life, nutritional status, glucose control, and hospitalizations at six and twelve months in a retrospective review of 48 adult patients with diabetes who received a gastric electrical stimulation implant. (7) The review also noted that gastric emptying was not significantly faster.  The authors subsequently reported intention-to-treat analysis of these patients at a follow-up of 45 months. (8) The improvements reported at 12 months follow-up were sustained beyond three years.  Mason and colleagues reported on the 20-month follow-up of 27 of 29 patients referred for gastrectomy who instead received GES for refractory gastroparesis. (9) Three patients required additional procedures due to poor outcomes.  Nutritional support was discontinued in the 19 patients who were dependent on supplemental feeding prior to the procedure.  Gastric emptying rates also improved.

The available intermediate and long-term data indicate that gastric electrical stimulation may be associated with improvements in gastrointestinal symptom scores, nutrition and quality-of-life for patients with gastroparesis of diabetic or idiopathic origin and that these improvements are sustained over time.

An updated search of the MEDLINE database through October 10, 2008 failed to return any new randomized clinical trials.  Anand and colleagues reported on a study of 214 consecutive drug-refractory patients with the symptoms of gastroparesis (146 idiopathic, 45 diabetic, 23 after surgery). (14) A gastric electrical stimulation device was implanted in 156 patients. The remaining 58 patients, designated as the control group, were either on the waiting list for permanent implantation or consented to not receive a permanent implant. At last follow-up (median four years), most patients who received implants (135 of 156) were alive with intact devices, significantly reduced gastrointestinal symptoms, and improved health-related quality of life, with evidence of improved gastric emptying. Also, 90% of the patients had a response in at least one of three main symptoms. Most patients explanted, usually for pocket infections, were later re-implanted successfully. Based on a series of 15 patients, Gourcerol reported that high-frequency gastric electrical stimulation could be an effective therapy for treating intractable nausea and vomiting, whether or not gastric emptying was delayed. (15)

Gastric Stimulation for the Treatment of Obesity

Gastric electrical stimulation is also proposed as a method of weight reduction in morbidly obese individuals. Gastric stimulation may make patients feel full with less food.  Small clinical trials have reported positive outcomes in weight loss and maintenance of weight loss along with minimal complications.  (10-13) However, due to lack of long term outcomes from well-designed randomized clinical trials, conclusions cannot be made concerning the safety and efficacy of chronic gastric stimulation in morbidly obese individuals. No gastric electrical stimulation devices have received FDA approval for treatment of obesity.

An updated search of the MEDLINE database returned no new published studies of gastric electrical stimulation in the treatment of obesity and gastroparesis that alter the conclusions reached above.

References

1. BlueCross and BlueShield Association Medical Policy Reference Manual, Policy No.7.01.73
2. FDA Web site address: www.fda.gov/cdrh/ode/H990014sum.html  (Verified 10/10/08)
3. Abell T, McCallum R, Hocking M, et al. Gastric electrical stimulation for medically refractory gastroparesis. Gastroenterology 2003;125(2):421-28
4. Abell T, Lou J, Tabbaa M, et al. Gastric electrical stimulation for gastroparesis improves nutritional parameters at short, intermediate, and long term follow-up. J Parenteral Enteral Nutr 2003;27(4):277-81
5. Forster J, Sarosiek I, Lin Z, et al. Further experience with gastric stimulation to treat drug refractory gastroparesis. Am J Surg 2003;186(6):690-5
6. van der Voort IR, Becker JC, Dietl KH, et al. Gastric electrical stimulation results in improved metabolic control in diabetic patients suffering from gastroparesis.  Exp Clin Endocrinol Diabetes 2005;113:38-42
7. Lin Z, Forster J, Sarosiek I, et al. Treatment of diabetic gastroparesis by high-frequency gastric electrical stimulation. Diabetes Care 2004;27(5):1071-6
8. Lin Z, Forster J, Sarosiek I, et al. Symptom responses, long-term outcomes and adverse events beyond 3 years of high-frequency gastric electrical stimulation for gastroparesis. Neurogastroenterol 2006;19(1):18-27
9. Mason RJ, Lipham J, Eckerling G et al. Gastric electrical stimulation: an alternative surgical therapy for patients with gastroparesis. Arch Surg 2005;140(9):841-6
10. Favretti F, De Luca M, Segato G, et al.  Treatment of morbid obesity with the Transcend Implantable Gastric Stimulator (IGS): a prospective survey.  Obes Surg 2004;14(5)666-70
11. Shikora SA. Implantable gastric stimulation for the treatment of severe obesity. Obes Surg 2004;14(4):545-8
12. Cigaina V. Gastric pacing as therapy for morbid obesity: preliminary results. Obes Surg 2002;12 Suppl 1:12S-16S
13. De Luca M, Segato G, Busetto L, et al.  Progress in implantable gastric stimulation: summary of results of the European multi-center study. Obes Surg 2004;14(Suppl.1):S33-9
14. Anand C, Al-Juburi A, Familoni B et al. Gastric electrical stimulation is safe and effective: a long-term study in patients with drug refractory gastroparesis in three regional centers. Digestion 2007;75(2-3):83-9
15. Gourcerol G, Leblanc I, Leroi AM et al. Gastric electrical stimulation in medically refractory nausea and vomiting. Eur J Gastroenterol Hepatol 2007;19(1):29-35

Cross References

Enteral and Oral Nutrition Therapy; Regence Medical Policy Manual, Allied Health Policy No. 5

Surgery for Morbid Obesity; Regence Medical Policy Manual, Surgery Policy No. 58

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