Thèse de doctorat
Résumé : This thesis aims at optimising gastric electrical stimulation (GES) as a therapy against obesity.Obesity has reached pandemic proportions in the 21st century. It is associated with major health issues and has considerable economic and societal costs worldwide. Bariatric surgery is an efficient yet invasive solution, and there are still concerns regarding its procedure-related complication and mortality rates. As an alternative, GES has been investigated in the last few decades with promising pre-clinical results, but further research is needed to overcome current gastrostimulator limits and to offer optimised weight-loss therapy to patients. Therefore, this work presents an implantable device designed to provide a broad range of stimulation patterns, remotely rechargeable and programmable, and implantable by a minimally invasive surgical procedure.To provide minimally invasive surgery, a specific electrode system was characterised and validated in vivo. The device materials and shape were optimised to provide the best anchoring stability while being compatible with the implantation procedure ergonomics. A single port percutaneous procedure was validated on a dog cadaver and in vivo, aiming to secure the electrodes in a single-step release, with dedicated anchoring system and tools. The tools have been designed and manufactured in stainless steel. Compared to widely used multi-port laparoscopy, our single dilated access technique (12 mm of diameter) was proven feasible, safe (no complication in vivo), quick (estimated to 15 minutes for electrode placement), and resulting in a small visible scar (< 5 mm).An implantable gastric stimulator (IGS) has been designed and validated. Its parameter range was selected to optimally impact the gastric motility and promote satiety feeling. The electronic system embeds a bidirectional controllable current source, an inductive power and communication link, and the external systems with graphical interfaces to fully control the stimulation protocol. With respect to existing devices, a higher energy, longer width, stimulation output stage was implemented based on an H-bridge topology. A dual switch LSK strategy was developed and has shown interesting properties compared to the literature. Depending on use, the system can operate for days to weeks without recharging and is designed for a lifetime of several years.With this gastrostimulator, we validated an adaptive GES protocol, which increases the stimulation energy proportionally to the excess of food intake with respect to a desired target. This adaptive protocol was assessed in vivo in five dogs in a cross over experiment over 3 months. Food intake, food intake rate and weight gain were significantly reduced in the stimulated group versus the sham one, and the postprandial electrogastrogram frequency was accelerated by GES. Those results allowed us to conclude on the benefit of adaptive GES on food intake and weight regulation. The versatility of the IGS and the minimally invasive anchoring system opens the path to many other applications, with little design adaptations, such as the treatment of gastroparesis or urinary bladder monitoring and stimulation. Altogether, this thesis contributed to the optimisation of GES therapy as an alternative to bariatric surgery, by proposing a minimally invasive implantation procedure, a GES specific IGS, and an adaptive stimulation protocol.