Table 7.

Efficacy of several bioelectric therapies in gastroparesis

Device/trial design	Patients	Efficacy	Reference
Vagal Stimulation
Open-label pilot study: short-term noninvasive cervical vagal nerve stimulation in patients with drug-refractory gastroparesis	23 patients with gastroparesis for 3 weeks and 7 of these for 6 weeks.	Response rates were 35% at 3 weeks and 43% for 3–6 weeks. Improvements in mean total GCSI and subscales were noted.	Paulon 2017, ref. 117
Open-label pilot study: noninvasive vagal nerve stimulation for 4 wks improves symptoms and gastric emptying in patients with IG	15 patients with mild to moderate IG	Improvement in total GCSI symptom scores and three subscales, with 40% participants meeting primary endpoint; therapy also associated with a reduction in GE T1/2.	Gottfried-Blackmore 2020, ref. 118
Spinal Cord Stimulation
Open-label study of spinal stimulation in patients with abdominal pain, with the majority having gastroparesis	23 patients, 96% Caucasian and 79% women, with gastroparesis in 63%	After 12 months of 10-KHZ spinal cord stimulation, 78% of patients had >50% reduction in pain and 64% remitted in pain. Other outcomes improved in most patients.	Kapural 2020, ref. 119
Controlled Trials in Gastric Electric Stimulation (GES)
Temporary GES
RCT, PC, XO trial of two consecutive, 4-day sessions of temporary GES	58 patients (47 females) with gastroparesis symptoms: 38 IG; 13 DG, 7 PSG	Overall slight, NS daily decrease in average vomiting scores First session was significant, but not significant after XO. Temporary GES may improve symptoms such as vomiting.	Abell T 2011, ref. 120
Permanent GES
GES reduces refractory vomiting in a randomized, XO trial	218 patients in 19 centers, 97 with DG and 121 with IG were included and 46 were excluded, thus 172 patients were implanted and analyzed	A randomized, XO trial for 4 months of GES decreased vomiting in DG and IG, irrespective of baseline GE.	Ducrotte 2020, ref. 121
Multicenter, DB, XO, RCT of GES	17 DG and 16 IG	Self-reported vomiting frequency significantly reduced in the on vs. off period and consistent with the significant patient preference for the on vs. off period; vomiting frequency decreased, and symptom severity and quality of life improved at 6 and 12 months. Once unblinded, the symptom improvement continued at one year.	Abell T 2003, ref. 122
Randomized XO study of GES with all patients turned on for 6 weeks and then with consecutive 3-month XO periods with device on or off	55 patients with DG	6 weeks of GES therapy significantly reduced vomiting and gastroparetic symptoms in patients with DG.	McCallum R 2010, ref. 123
Prospective, DB, randomized, XO study of GES with all patients initially having device on for 6 weeks followed by DB consecutive 3-month XO periods with device either on or off.	32 patients with IG	GES implanted with on stimulation was shown to decrease vomiting symptoms in the initial 6-week on period. NS reduction in vomiting symptoms in on vs. off period. Sustained decrease in vomiting and days of hospitalization at 12 months in the on group.	McCallum R 2013, ref. 124
Two separate but related studies of the effect of GES on pancreatic function in gastroparesis patients: single-blinded, RCT compared to normal controls	9 patients with gastroparesis and GES and 9 healthy controls	Pancreatic elastase was significantly different for GES on vs. off: 508 on vs. 378 off. Total GI symptoms were significantly lower on vs. off. Pancreatic polypeptide and heart rate were borderline improved with on vs. off.	Luo 2004, ref. 125
DB, prospective, single-arm, RCT Study of GES in DG	7 DG patients	No evidence was found for GES-induced modulation of the visceral sensory system and central excitability. Some changes in symptoms noted with GES.	Frokjaer 2009, ref. 126
Propensity score matching. Effect of GES in gastroparesis with prospective data	319 patients with gastroparesis symptoms, of which, 81 had GES and 231 without GES	Patients treated with GES had clinically significant improvement in gastroparesis symptoms. When adjusted by propensity scoring only nausea remained significant	Abell T 2019, ref. 127
Controlled with medical arm but not randomized study with 1 year of baseline and 3 years of treatment with two groups: GES vs intensive medical therapy	9 GES patients and 9 similar patients in an outpatient medical program	GES was found to be more effective in improving long-term GI symptoms, decreased costs, and less use of healthcare resources than intensive medical therapy.	Cutts 2005, ref. 128
Meta-analyses Assessing Effectiveness of Gastric Electrical Stimulation
NICE Guidance on GES for gastroparesis	Several studies reviewed, 2 metanalysis, 2 RCT, XO	Diabetics with severe symptoms may benefit from therapy.	Kong 2015, ref. 129
SRMA 13 studies, 12 lacked controls and 1 blinded and randomized	13 studies, 12 lacked controls and 1 blinded and randomized	Following GES, improvements in TSS score (3/13 studies), vomiting severity (4/13), nausea severity (4/13), SF-36 physical composite score (4/13), SF-36 mental composite score (4/13), requirement for enteral or parenteral nutrition (8/13), and 4-h gastric emptying (5/13). Weight gain (in 3/13) did not reach overall significance, 3 Device removal or reimplantation rate was 8.3%. Beneficial in improving symptoms in patients with gastroparesis	O’Grady 2009, ref. 130
SRMA 5 studies randomly allocated patients to periods with or without GES	5 randomized trials 16 open-label studies	TSS scores did not differ between these periods with or without GES in randomized trials. Open-label studies showed a significant decrease in TSS scores, which was also shown with medical therapy or placebo arms, or botulinum toxin. Meta-regression analysis showed that significant differences in baseline TSS ratings impacted TSS ratings during treatment. Argues against the use of GES outside of strict clinical trials as viable treatment option.	Levinthal 2017, ref. 131
SRMA	21 studies	GES appears to offer significant improvement in symptom control in a subset of patients.	Lal 2015, ref. 132
SRMA	10 studies	GES is an effective modality for treating gastroparesis refractory to less invasive treatment.	Chu 2012, ref. 133
Selected Open-Label Trials of Gastric Electrical Stimulation
Multicenter, open-label GES experience in France	142 patients (60 diabetic, 82 non-diabetic) and medico-economic data were available for 96 patients (36 diabetic, 60 non-diabetic)	24 months after implantation. GIQLI score increased, with a more significant improvement in non-diabetic than in diabetic patients. Proportion of patients vomiting less than once per month increased by 25.5%. GES decreased mean overall healthcare costs (saving of average $3348/patient/year), with. savings greater for diabetic patients (4096 US$/patient/year).	Gourcerol 2020, ref. 134
Open-label GES study	16 patients with PSG refractory to medical therapy	Severity and frequency of all 6 upper GI symptoms, TSS, physical composite score, and mental composite score significantly improved after 6 months and sustained at 12 months; 4/7 stopped jejunal feeding; mean number of hospitalization days significantly reduced by a mean 25 days compared with prior year. No effect on GE.	McCallum 2005, ref. 135
Open-label GES study	37 gastroparesis patients preop. and 1y post-GES implant	8/27 off prokinetics; 9/26 off antiemetics at 1y; mean TSS significantly reduced, overall SF-36 scores (HR-QOL) significantly improved, and hospitalizations decreased from 50 ± 10 days for the year prior to GES therapy to 14 ± 3 days. GE was not significantly improved.	Lin 2005, ref. 136
Open-label GES study	55 patients with gastroparesis with follow-up information for over 3y	Of the 55 patients, 10 died of unrelated complications, 6 had devices removed and 2 could not be reached. 37 patients had activated GES for mean 45 months: TSS, hospitalization days and the use of medications all significantly reduced at 1 and 3 y. Among 15/37 patients requiring nutritional support, only 5 continued beyond 3y. Mean HbA1c in diabetics reduced from 9.5 to 7.9% at 3y.	Lin 2006, ref. 137
Open-label GES study	15 patients with gastroparesis	Four patients (4 idiopathic) failed to improve more than 20% on multiple assessments after a year of therapy. All diabetic patients experienced a durable symptomatic improvement with GES. GES non-responders had less severe vomiting preoperatively.	Musunuru 2010, ref. 138
Open-label GES clinical experience	221 patients with gastroparesis: 142 (64%) DG, 48 (21%) IG, 31 (14%) PSG	At follow-up of at least 1 year, there was association of symptom improvement with improved GE in DG, not in IG. Patient age, gender, baseline TSS score, and baseline gastric retention had no significant effect on clinical improvement in response to GES.	Hou 2012, ref. 139
Open-label experience	4 patients with gastroparesis	Mean length of hospital stay in the year pre-GES was 81.75 days and 62.25 days in the year post-GES; also no improvement in glycemic control following GES.	Hannon 2011, ref. 140
Open-label follow-up study of GES after successful initial temporary GES	IG 9, DG 3 with long duration symptoms (7.3 years)	Short-term: improved TSS, body weight, BMI, and serum albumin by 3 to 6 months. Intermediate (1 to 2 years) and long-term (5 year) data: continued improvement in TSS, weekly vomiting frequency score, QOL measures, and maintained weight gain.	Abell T 2003, ref. 141
Open-label GES study	Refractory gastroparesis: DG 39, PSG 9, IG 7	TSS and the physical and mental composite scores of QOL improved significantly; GE did not change; BMI and body weight increased; days spent in hospital admissions significantly decreased.	Forster 2003, ref. 142

DG=diabetic gastroparesis; DM=diabetic; GCSI=Gastroparesis Cardinal Symptom Index; GE=gastric emptying; GES=gastric electrical stimulation; GIQLI=Gastrointestinal quality of life; HR-QOL=health-related quality of life; IG=idiopathic gastroparesis; NA=not available; NS=not significant; PC=placebo-controlled; po=oral; PG=parallel-group; PSG=post-surgical gastroparesis; RCT=randomized, controlled trial; TSS=total symptom severity; XO=crossover