International clinical research progress on implantable gastric electrical stimulation

In 1998, a second human trial was conducted to study the safety and efficacy of the first-generation gastric stimulator, the Prelude implantable gastric stimulator system. All enrolled patients had a BMI greater than 40, a history of unsuccessful weight loss, and no serious heart, respiratory, or mental health problems.

Ten patients underwent minimally invasive surgery to implant the device, followed by continuous stimulation for 30 days. All subjects were allowed to eat and drink freely during mealtimes, but were prohibited from eating between meals. Sweets and alcoholic beverages were also prohibited for all subjects. Patients were followed up approximately monthly via a percutaneous radiofrequency remote control system connected to the implanted device and computer system. The stimulation parameters, lead impedance, and remaining battery capacity of the gastric stimulator were calibrated.

This study was safe and effective, with no deaths or other significant medical problems, operational complications, or long-term comorbidities during the study period. In particular, there were no lead breaks or device electronic component malfunctions.

After 51 months of electrical stimulation, the 10 patients lost an average of 23% of their excess weight and maintained good health. Weight regain occurred when the battery depleted, but weight loss resumed after battery replacement.

**Current international experience with implantable gastric electrical stimulation for weight loss**

An implantable gastric electrical stimulation device is a pacemaker-like device consisting of a battery-powered pulse generator and bipolar leads. The generator, similar in size to a pocket watch, is implanted subcutaneously in the upper left quadrant of the abdominal wall.

The device leads are implanted laparoscopically into the serosal layer of the anterior gastric wall. The procedure usually takes less than an hour, and most patients can be discharged on the same day or the following day.

The programmer is a standard computer connected to a programming and recognition device. The programmer communicates with the implanted IGS via transcutaneous radiofrequency remote control through the computer and recognition device. In clinical practice or field settings, IGS can be quickly and easily monitored or programmed. Currently, over 800 patients worldwide have participated in this research trial and received implanted IGS devices; there have been no deaths or major complications.

**European Multicenter Study**

Following the pioneering study by Cigaina et al., a multicenter trial was conducted in Europe. Fifty patients received IGS implantation at seven clinical centers. Each clinical center had a slightly different trial design, but all were open-label trials.

None of the patients developed significant complications, and after a two-year follow-up period, the patients' average excess weight decreased by more than 40%.

**Laparoscopic Obesity Stimulation Study**

Another multicenter study was conducted in Europe. Initially, 60 patients from eight participating sites enrolled. Similar to the previous study, no significant complications occurred. After a 10-month follow-up period, excess weight was reduced by an average of over 20%. For 91 patients, the average excess weight reduction remained at 25% two years after implantation.

**US O-01 Trial**

In the United States, the first study evaluating the safety and efficacy of the IGS device was a multicenter, randomized, controlled, double-blind trial involving 103 patients. IGS leads were implanted laparoscopically in 100 patients.

One month after implantation, patients were randomly assigned to either activate their devices or keep them in deactivated mode. Seven months later, devices in the deactivated group were activated. All patients had identical device settings. Patients underwent monthly clinical assessments for 24 months, with close monitoring for complications and weight loss. No dietary or behavioral counseling was provided to participants.

There have been no deaths or complications related to implantation to date. Although no patients experienced adverse reactions during this trial, 17 of the initial 41 leads detached from the stomach wall. This prompted technological updates to ensure improved lead safety.

However, it is almost certain that lead detachment will affect weight loss results. Furthermore, a lack of dietary or behavioral counseling, and the presence of patients with bulimia nervosa, may also negatively impact weight loss outcomes.

Interestingly, many patients admitted to intentionally binge eating or trying various foods during the first six months to determine if their internal mechanisms were activated. Despite these adverse factors, after one year of stimulation, 20% of the patients lost more than 5% of their total body weight, and the experimental group experienced an average weight loss of 11% of their total body weight.

**American Dual-Lead Implantable Gastric Electrical Stimulation Trial**

Based on the results of a European multicenter study and the US O-01 trial, a preliminary trial was designed in the US to determine whether the treatment efficacy could be further improved. The dual-lead implantable gastric electrical stimulation trial was an open-label trial that enrolled 30 patients from two clinical centers.

This experiment is unique for several reasons: ① It excluded those who binge eat, as their symptoms were not obvious in the early stages of the experiment; ② It provided behavioral guidance and dietary counseling to the participants during the experiment; ③ The device has two leads that can be controlled separately or in combination; ④ The stimulation program was tailored to the specific circumstances of each patient.

An early breakthrough in the study was that most patients immediately experienced bloating, nausea, retching, or abdominal pain during the high-output program. This finding may be similar to capturing a heart rhythm during pacing. The output was subsequently reduced to below the symptom threshold.

Most patients experiencing the above symptoms also experienced a severe decrease in appetite, and most achieved their weight loss goals. Excess weight was reduced by 15% at 38 weeks and by 23% at 16 months.

However, at our center, after an average follow-up of 9.5 months, the average excess weight loss was 30.4%; 80% of patients experienced varying degrees of weight loss, and 60% of patients lost more than 10% of their excess weight. The significantly different results obtained from the two research centers reflect differences in patient selection and management processes, highlighting the importance of selecting appropriate patients and providing support.

**Patient Selection Considerations**

To date, trials worldwide on IGS devices have demonstrated that they can achieve weight loss effects like all other surgical treatments; however, no single treatment is suitable for all patients.

We developed a simple patient screening tool and used it to retrospectively analyze approximately 252 IGS participants internationally. This screening tool, based on demographic and questionnaire item feedback, accurately predicts treatment responders and non-responders.

Patients' desire and motivation to undergo treatment appear to be the most important factors. Using this screening tool, some subjects classified as responders showed significantly better treatment outcomes with IGS than those predicted to be non-responders.

At two U.S. centers conducting IGS clinical trials, this screening tool excluded approximately 75% of the 252 participants. However, those who qualified under this tool all achieved remarkably good weight loss. Future prospective analyses are needed to further validate these preliminary findings.

On the surface, screening out 75% of potential patients might seem to hinder the future development and application of this technology. However, for hundreds of millions of obese patients, even if only 25% can benefit from this technology, it is still a considerable number.