Gastroparesis

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 diabetic patients. While most commonly associated with diabetes, gastroparesis is also found in chronic pseudo-obstruction, connective tissue disorders, Parkinson disease, and psychological pathologic conditions. Some cases may not be associated with an identifiable cause and are referred to as idiopathic gastroparesis. Treatment of gastroparesis includes prokinetic agents (eg, metoclopramide) and antiemetic agents (eg, metoclopramide, granisetron, ondansetron). Severe cases may require enteral or total parenteral nutrition.

Treatment

Gastric electrical stimulation (GES), also referred to as gastric pacing, using an implantable device, has been investigated primarily as a treatment for gastroparesis. Currently available devices consist of a pulse generator, which can be programmed to provide electrical stimulation at different frequencies, connected to intramuscular stomach leads, which are implanted during laparoscopy or open laparotomy (see Regulatory Status section).

Obesity

GES has also been investigated as a treatment of obesity. It is used to increase a feeling of satiety with subsequent reduction in food intake and weight loss. The exact mechanisms resulting in changes in eating behavior are uncertain but may be related to neurohormonal modulation and/or stomach muscle stimulation.

Regulatory Status

In 2000, the Gastric Electrical Stimulator system (now called Enterra™ Therapy System; Medtronic) was approved by the U.S. Food and Drug Administration through the humanitarian device exemption process (H990014) for the treatment of gastroparesis. The GES system consists of 4 components: the implanted pulse generator, 2 unipolar intramuscular stomach leads, the stimulator programmer, and the memory cartridge. With the exception of the intramuscular leads, all other components have been used in other implantable neurologic stimulators, such as spinal cord or sacral nerve stimulation. The intramuscular stomach leads are implanted either laparoscopically or during laparotomy and are connected to the pulse generator, which is implanted in a subcutaneous pocket. The programmer sets the stimulation parameters, which are typically set at an “on” time of 0.1 seconds alternating with an “off” time of 5.0 seconds.

Currently, no GES devices have been approved by the Food and Drug Administration for the treatment of obesity. The Transcend® (Transneuronix; acquired by Medtronic in 2005), an implantable gastric stimulation device, is available in Europe for treatment of obesity.

Related Policies

• Vagus Nerve Stimulation (VNS) (Policy #014 in the Surgery Section)
• Vagus Nerve Blocking Therapy for Treatment of Obesity (Policy #151 in the Surgery Section)

• severe nausea and vomiting (occurring on average at least once daily); and
• refractory to aggressive antiemetic and prokinetic drug therapy.

(NOTE: Currently, only 1 gastric electrical stimulator has received approval from the FDA, the Gastric Electrical Stimulator (GES) system - now called Enterra Therapy System - manufactured by Medtronic Inc. The GES system received FDA approval through a humanitarian device exemption (HDE) in March 2000. According to the FDA, devices approved through the HDE process may only be used in facilities that have an institutional review board (IRB) to supervise clinical testing of the device.)

[RATIONALE: This policy was created in 2000 and has been updated regularly with searches of the MEDLINE database. The most recent literature update was performed through January 3, 2019.

Evidence reviews assess the clinical evidence to determine whether the use of a technology improves the net health outcome. Broadly defined, health outcomes are length of life, quality of life, and ability to function¾including benefits and harms. Every clinical condition has specific outcomes that are important to patients and to managing the course of that condition. Validated outcome measures are necessary to ascertain whether a condition improves or worsens; and whether the magnitude of that change is clinically significant. The net health outcome is a balance of benefits and harms.

To assess whether the evidence is sufficient to draw conclusions about the net health outcome of a technology, 2 domains are examined: the relevance and the quality and credibility. To be relevant, studies must represent one or more intended clinical use of the technology in the intended population and compare an effective and appropriate alternative at a comparable intensity. For some conditions, the alternative will be supportive care or surveillance. The quality and credibility of the evidence depend on study design and conduct, minimizing bias and confounding that can generate incorrect findings. The randomized controlled trial (RCT) is preferred to assess efficacy; however, in some circumstances, nonrandomized studies may be adequate. RCTs are rarely large enough or long enough to capture less common adverse events and long-term effects. Other types of studies can be used for these purposes and to assess generalizability to broader clinical populations and settings of clinical practice. The following is a summary of the key literature to date.

GES for Obesity

Clinical Context and Test Purpose

The purpose of gastric electrical stimulation is to provide a treatment option that is an alternative to or an improvement on existing therapies, such as conservative management, medication, and bariatric surgery in patients with obesity.

The question addressed in this policy is: does gastric electrical stimulation improve the net health outcome for patients with obesity?

The following PICOTS were used to select literature to inform this review.

Patients

The relevant population of interest are individuals with obesity.

Interventions

The therapy being considered is gastric electrical stimulation.

Comparators

Comparators of interest include conservative management, medication, and bariatric surgery. Treatment includes physical exercise, low carbohydrate dieting, and low-fat dieting.

Outcomes

The general outcomes of interest are change in disease status and treatment-related morbidity.

Timing

The existing literature evaluating gastric electrical stimulation as a treatment for obesity has varying lengths of follow up, ranging from 1 year. While studies described below all reported at least one outcome of interest, longer follow-up was necessary to fully observe outcomes. Therefore, 1 year of follow-up is considered necessary to demonstrate efficacy.

Setting

Patients with obesity are actively managed by nutritionists and primary care providers in an outpatient clinical setting.

Study Selection Criteria

Methodologically credible studies were selected using the following principles: 

a.     To assess efficacy outcomes, comparative controlled prospective trials were sought, with a preference for RCTs;

b.     In the absence of such trials, comparative observational studies were sought, with a preference for prospective studies.

c.     To assess longer term outcomes and adverse events, single-arm studies that capture longer periods of follow-up and/or larger populations were sought.

Studies with duplicative or overlapping populations were excluded.

A single RCT has evaluated the use of GES for treating obesity: the SHAPE trial. Shikora et al (2009) reported on a double-blind RCT that assessed GES obesity.^10, All 190 trial participants received an implantable gastric stimulator and were randomized to have the stimulator turned on or off. All patients were evaluated monthly, participated in support groups, and reduced their dietary intake by 500 kcal/d. At 12-month follow-up, there was no statistically significant difference in excess weight loss between the treatment group (weight loss, 11.8%) and the control group (weight loss, 11.7%) using intention-to-treat analysis (p=0.717).

Small case series and uncontrolled prospective trials (2002-2004) have reported positive outcomes for weight loss and maintenance of weight loss along with minimal complications.^{11,12,13,14,15,16,} However, interpretation of these uncontrolled studies is limited.

Summary of Evidence

For individuals who have obesity who receive GES, the evidence includes an RCT. Relevant outcomes are change in disease status and treatment-related morbidity. The SHAPE trial did not show significant improvement in weight loss using GES compared with sham stimulation. The evidence is insufficient to determine the effects of the technology on health outcomes.

SUPPLEMENTAL INFORMATION

Clinical Input From Physician Specialty Societies and Academic Medical Centers

While the various physician specialty societies and academic medical centers may collaborate with and make recommendations during this process, through the provision of appropriate reviewers, input received does not represent an endorsement or position statement by the physician specialty societies or academic medical centers, unless otherwise noted.

2015 Input

In response to requests, input was received from 1 specialty society (2 reviewers) and 4 academic centers while this policy was under review in 2015. Most respondents agreed that gastric electrical stimulation (GES) should be considered investigational for gastroparesis. There was a lack of consensus whether GES should be considered medically necessary for any specific indication (eg, diabetic gastroparesis, idiopathic gastroparesis, gastroparesis of postsurgical etiology). The reviewers were not asked about the use of GES for treatment of obesity.

2009 Input

In response to requests, input was received from 4 academic medical centers (5 reviewers) while this policy was under review in 2009. There was strong agreement among reviewers about the limited data for the use of GES to treat diabetic and idiopathic gastroparesis and about the need for randomized controlled trials. There was strong agreement that GES is investigational in the treatment of obesity.

Practice Guidelines and Position Statements

National Institute for Health and Care Excellence

The National Institute for Health and Care Excellence (2014) has issued guidance on GES for gastroparesis.^17, The Institute made the following recommendations:

1.1  “Current evidence on the efficacy and safety of gastric electrical stimulation for gastroparesis is adequate to support the use of this procedure with normal arrangements for clinical governance, consent, and audit.

1.2  … clinicians should inform patients considering gastric electrical stimulation for gastroparesis that some patients do not get any benefit from it. They should also give patients detailed written information about the risk of complications, which can be serious, including the need to remove the device.

1.3  Patient selection and follow-up should be done in specialist gastroenterology units with expertise in gastrointestinal motility disorders, and the procedure should only be performed by surgeons working in these units.

American College of Gastroenterology

The American College of Gastroenterology published practice guidelines on the management of gastroparesis in 2013.^18, The College recommended that:

“GES [gastric electrical stimulation] may be considered for compassionate treatment in patients with refractory symptoms, particularly nausea and vomiting. Symptom severity and gastric emptying have been shown to improve in patients with DG [diabetic gastroparesis], but not in patients with IG [idiopathic gastroparesis] or PSG [postsurgical gastroparesis]. [Conditional recommendation (there is uncertainty about trade-offs), moderatelevel of evidence (further research would be likely to have an impact on the confidence in the estimate of effect).]”

U.S. Preventive Services Task Force Recommendations

Not applicable.

Ongoing and Unpublished Clinical Trials

Some currently unpublished trials that might influence this review are listed in Table 5.

Table 5. Summary of Key Trials

NCT No.	Trial Name	Planned Enrollment	Completion Date
Ongoing
NCT03261531a	Dermatome Electrical Stimulation on Individuals With Overweight and Class I Obesity	16	Mar 2018

NCT: national clinical trial.

^a Denotes industry-sponsored or cosponsored trial.]
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Horizon BCBSNJ Medical Policy Development Process:

This Horizon BCBSNJ Medical Policy (the “Medical Policy”) has been developed by Horizon BCBSNJ’s Medical Policy Committee (the “Committee”) consistent with generally accepted standards of medical practice, and reflects Horizon BCBSNJ’s view of the subject health care services, supplies or procedures, and in what circumstances they are deemed to be medically necessary or experimental/ investigational in nature. This Medical Policy also considers whether and to what degree the subject health care services, supplies or procedures are clinically appropriate, in terms of type, frequency, extent, site and duration and if they are considered effective for the illnesses, injuries or diseases discussed. Where relevant, this Medical Policy considers whether the subject health care services, supplies or procedures are being requested primarily for the convenience of the covered person or the health care provider. It may also consider whether the services, supplies or procedures are more costly than an alternative service or sequence of services, supplies or procedures that are at least as likely to produce equivalent therapeutic or diagnostic results as to the diagnosis or treatment of the relevant illness, injury or disease. In reaching its conclusion regarding what it considers to be the generally accepted standards of medical practice, the Committee reviews and considers the following: all credible scientific evidence published in peer-reviewed medical literature generally recognized by the relevant medical community, physician and health care provider specialty society recommendations, the views of physicians and health care providers practicing in relevant clinical areas (including, but not limited to, the prevailing opinion within the appropriate specialty) and any other relevant factor as determined by applicable State and Federal laws and regulations.

___________________________________________________________________________________________________________________________

Index:
Gastric Electrical Stimulation
Gastroparesis, Electrical Stimulation for
Electrical Stimulation of Gastroparesis
Enterra Therapy System
Pacing, Gastric Electrical
Stimulation, Gastric Electrical

References:
1. Levinthal DJ, Bielefeldt K. Systematic review and meta-analysis: Gastric electrical stimulation for gastroparesis. Auton Neurosci. Jan 2017;202:45-55. PMID 27085627

2. Chu H, Lin Z, Zhong L, et al. Treatment of high-frequency gastric electrical stimulation for gastroparesis. J Gastroenterol Hepatol. Jun 2012;27(6):1017-1026. PMID 22128901

3. Lal N, Livemore S, Dunne D, et al. Gastric electrical stimulation with the Enterra System: a systematic review. Gastroenterol Res Pract. Aug 2015;2015:762972. PMID 26246804

4. Abell T, McCallum R, Hocking M, et al. Gastric electrical stimulation for medically refractory gastroparesis. Gastroenterology. Aug 2003;125(2):421-428. PMID 12891544

5. U.S. Food and Drug Administration. Summary of Safety and Probable Benefit: Enterra™ Therapy System. 2010; http://www.accessdata.fda.gov/cdrh_docs/pdf/H990014b.pdf. Accessed January 25, 2018.

6. McCallum RW, Snape W, Brody F, et al. Gastric electrical stimulation with Enterra therapy improves symptoms from diabetic gastroparesis in a prospective study. Clin Gastroenterol Hepatol. Nov 2010;8(11):947-954; quiz e116. PMID 20538073

7. McCallum RW, Sarosiek I, Parkman HP, et al. Gastric electrical stimulation with Enterra therapy improves symptoms of idiopathic gastroparesis. Neurogastroenterol Motil. Oct 2013;25(10):815-e636. PMID 23895180

8. Laine M, Siren J, Koskenpato J, et al. Outcomes of High-Frequency Gastric Electric Stimulation for the Treatment of Severe, Medically Refractory Gastroparesis in Finland. Scand J Surg. Jun 2018;107(2):124-129. PMID 29268656

9. Shada A, Nielsen A, Marowski S, et al. Wisconsin's Enterra Therapy Experience: A multi-institutional review of gastric electrical stimulation for medically refractory gastroparesis. Surgery. Oct 2018;164(4):760-765. PMID 30072246

10. Shikora SA, Bergenstal R, Bessler M, et al. Implantable gastric stimulation for the treatment of clinically severe obesity: results of the SHAPE trial. Surg Obes Relat Dis. Jan-Feb 2009;5(1):31-37. PMID 19071066

11. Cigaina V. Gastric pacing as therapy for morbid obesity: preliminary results. Obes Surg. Apr 2002;12 Suppl 1:12S-16S. PMID 11969102

12. Cigaina V, Hirschberg AL. Gastric pacing for morbid obesity: plasma levels of gastrointestinal peptides and leptin. Obes Res. Dec 2003;11(12):1456-1462. PMID 14694209

13. D'Argent J. Gastric electrical stimulation as therapy of morbid obesity: preliminary results from the French study. Obes Surg. Apr 2002;12 Suppl 1:21S-25S. PMID 11969104

14. 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. Sep 2004;14 Suppl 1:S33-39. PMID 15479588

15. 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. May 2004;14(5):666-670. PMID 15186636

16. Shikora SA. Implantable gastric stimulation for the treatment of severe obesity. Obes Surg. Apr 2004;14(4):545-548. PMID 15130236

17. National Institute of Health and Care Excellence. Gastroelectrical stimulation for gastroparesis [IPG489 ]. 2014; https://www.nice.org.uk/guidance/ipg489. Accessed January 25, 2018.

18. Camilleri M, Parkman HP, Shafi MA, et al. Clinical guideline: management of gastroparesis. Am J Gastroenterol. Jan 2013;108(1):18-37; quiz 38. PMID 23147521

Codes:
(The list of codes is not intended to be all-inclusive and is included below for informational purposes only. Inclusion or exclusion of a procedure, diagnosis, drug or device code(s) does not constitute or imply authorization, certification, approval, offer of coverage or guarantee of payment.)

CPT*

43647
43648
43881
43882
64590
64595
95980
95981
95982

L8680
L8685
L8686
L8687
L8688