Hypoglycemia Vagal Nerve Stimulation Therapy (HVNS Therapy)

Project Summary/Abstract 30.3 million Americans are diabetic w/ 1.5 million new cases per year. Hypoglycemia negatively affects diabetics. The average type 1 diabetic experiences 2 symptomatic hypoglycemia episodes/week. Severe hypoglycemia (need for 3rd party assistance) results in 1.0 – 1.7 episodes per patient per year. Annually, 73% of insulin dependent type 2 diabetics experience hypoglycemic episodes and 15% have severe episodes. Hypoglycemia can cause loss of consciousness, stroke, coma or death with repeated episodes linked to cardiovascular disease. Treatments typically involve consuming 15 grams of fast-acting carbohydrate. However, this treatment is not ideal for nocturnal hypoglycemia and contraindicated for severe hypoglycemic episodes. Insulin pumps w/ glucose sensor technology decreases hypoglycemia risk, but it still remains a meaningful problem. Less than 1% of insulin dependent diabetics use insulin pumps with issues of maintenance and tolerance required by continuous use of an external device. Thus, there is need for new treatment modalities for hypoglycemia. ReShape Lifesciences Inc. is developing an innovative approach to hypoglycemic control involving hypoglycemia vagal nerve stimulation (HVNS) using an implantable pulse generator interacting with a continuous glucose monitor (CGM). The HVNS System consists of an implantable pulse generator, stimulation leads attachable to posterior vagal nerve, a CGM and an external programmer to alter parameters to customize therapeutic effect. This HVNS system has shown efficacy by increasing plasma glucose (PG) in diabetic rat and diabetic pig models following insulin administration. We hypothesize that HVNS of PVN cranial to the celiac branch (shown to increase glucagon release) is an effective method to increase PG to a safe level during hypoglycemia. This NIH-SBIR Phase I study will successfully demonstrate feasibility of the HVNS system with the following specific aims: Specific Aim 1: Develop minimally invasive electrodes implantation technique. Specific Aim 2: Determine Effectiveness of HVNS and Non-Inferiority to Intranasal Glucagon. Specific Aim 3 Determine change in glucagon and insulin w/HVNS. Specific Aim 4 Determine the safety of stimulation on vagus nerve by demonstration of healthy nerve, pancreas, brain and liver histopathology ReShape Lifesciences has assembled an experienced team to complete this project which was previously developed HFAC technology to block sub-diaphragmatic vagus nerve for commercial use. The successful completion of this NIH SBIR Phase I study will allow an application for Phase II funding allowing the further development of HVNS hardware, larger scale Good Laboratory Practices (GLP) safety and efficacy studies in swine and development of regulatory strategies leading to the initiation of human trials.