The Safety and Efficacy of vBloc Therapy Delivered by the Maestro Rechargeable System for the Treatment of Obesity

Study Overview
=================
Brief Summary
-----------------
The study evaluated the safety and efficacy of the vBloc Therapy delivered by the Maestro Rechargeable System compared to a sham control for the treatment obesity. The Maestro Rechargeable System delivers intermittent, electrical blocking signals to the anterior and posterior trunks of the intra-abdominal vagus nerve (termed vBloc Therapy) and is designed to reduce sensations of hunger and produce satiety leading to weight loss. After approval from the institutional review board, subjects provided written consent and were randomized in a 2 to 1 allocation to vBloc group (with laparoscopic placement of the leads and neuroregulator) or the sham group (placement of a custom sham neuroregulator only) on double-blinded basis. Both groups received similar diet and exercise counseling. Weight, adverse events, clinical laboratories, ECGs, eating questionnaires and quality of life data were evaluated throughout the 12 month study duration.

Detailed Description
-----------------
The Maestro® Rechargeable System is a neuromodulation system. All subjects will be randomized in a 2:1 allocation to vBloc or Sham. All subjects will be followed through the 12-month follow-up visit. Subjects in the Sham group who choose to have an active device will undergo a second surgery to receive the active device after study unblinding.

Official Title
-----------------
A Randomized, Double Blind Sham Controlled Clinical Trial to Evaluate the Safety and Efficacy of vBloc Therapy Delivered by the Maestro Rechargeable System for the Treatment of Obesity

Conditions
-----------------
Obesity

Intervention / Treatment
-----------------
* Device: vBloc (Active Device)
* Device: Sham (Non-active Device)


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion criteria Signed informed consent Body mass index (BMI) ≥ 40 kg/m2 to 45 kg/m2 or BMI ≥ 35 kg/m2 to 39.9 kg/m2 with one or more obesity related co-morbid conditions. Co-morbid conditions may include one or more of the following: Type 2 diabetes mellitus as defined in inclusion criteria #5 (limited to 10% of randomized subjects) Hypertension as defined by systolic pressure ≥140 mmHg and/or diastolic pressure ≥90 mmHg a) treated or untreated with systolic ≥140 mmHg or diastolic ≥90 mmHg or b) treated with systolic <140 mmHg and diastolic <90 mmHg Dyslipidemia as defined by total cholesterol ≥200 or LDL ≥130 a) treated or untreated with total cholesterol ≥200 or LDL ≥130 or b) treated with total cholesterol <200 or LDL <130 Sleep apnea syndrome (confirmed by overnight p02 studies) Obesity-related cardiomyopathy Females or males Note: females of child-bearing potential must have a negative urine pregnancy test at Screen and also within 14 days of implant procedure followed by physician-approved contraceptive regimen for the duration of the study period. 18-65 years of age inclusive. Type 2 diabetes mellitus subjects: Glycosylated hemoglobin (HbA1c) 7.0 - 10.0 % inclusive at screening visit. (Undiagnosed subjects that are found to have a HbA1c value between 7-10% at screening must see their primary physician for diagnosis and medical treatment before continuing in trial) Onset: 12 years or less since initial diagnosis. Currently not using insulin therapy, GLP-1 (glucagon-like peptide-1) receptor agonists (e.g., exenatide, liraglutide) for diabetes treatment and have not been on these treatments in the past 6 months. Creatinine within normal reference range. No history of proliferative retinopathy. No history of peripheral neuropathy. No history of autonomic neuropathy. No history of coronary artery disease, with or without angina pectoris. No history of peripheral vascular disease. Failure to respond to supervised diet/exercise program(s) in which the subject was engaged within the last five years. Ability to complete all study visits and procedures. Exclusion criteria Concurrent chronic pancreatic disease. History of Crohn's disease and/or ulcerative colitis. History of bariatric surgery, fundoplication, gastric resection or major upper-abdominal surgery (acceptable surgeries include cholecystectomy, hysterectomy). History of pulmonary embolism or blood coagulation disorders. Clinically significant hiatal hernias (> 5 cm) known from subject's medical record or determined by barium swallow (upper GI x-ray) or upper endoscopy per PI discretion prior to implant. Current cirrhosis, portal hypertension and/or esophageal varices. Intra-operative exclusion: hiatal hernia requiring surgical repair or extensive dissection at esophagogastric junction at time of surgery. Treatment with prescription weight-loss drug therapy within the prior three months and the use of prescription drug therapy or the use of over-the-counter weight loss preparations for the duration of the trial. Smoking cessation within the prior six months. Known genetic cause of obesity (e.g., Prader-Willi Syndrome). Weight loss of more than 10% of body weight in the previous 12 months. Physician-prescribed diet with intent to lose weight prior to surgery (note: study subject may continue any personal eating plan they were on prior to study enrollment [see exclusion criterion #24] Current type 1 diabetes mellitus (DM). Current or recent history (within 12 months) of ongoing bulimia. Current alterations in treatment for thyroid disorders (stable treatment regimen for prior three months acceptable). Current alterations in treatment for epilepsy (stable treatment regimen for prior six months acceptable). Current treatment for peptic ulcer disease (previous history acceptable). Chronic (more than 4 weeks of daily use) treatment with narcotic analgesic drug regimens (treatment with non-steroidal anti-inflammatory drugs acceptable). Current alterations in treatment regimens of anti-cholinergic drugs, including tricyclic antidepressants (stable treatment regimen for prior six months acceptable). Current medical condition that, in the opinion of the investigator, would make subject unfit for surgery under general anesthesia or that would be exacerbated by intentional weight loss. Some examples include diagnosis of cancer, recent heart attack, recent stroke, or recent serious trauma. Presence of permanently implanted electrical powered medical device or implanted gastrointestinal device or prosthesis (e.g., pacemakers, implanted defibrillators, neurostimulators etc.). Planned or contemplated use of Magnetic Resonance Imaging (MRI) or oncologic radiation during the course of the trial. Psychiatric disorders (including untreated severe depression, schizophrenia, substance abuse, bulimia nervosa, etc.) or limited intellectual functioning which would potentially compromise the participant's ability to fully comprehend and/or cooperate with the study protocol. Psychiatric disorders will be established by a review of subject's medical history. For depression, a BDI (Beck Depression Inventory) score ≥ 29 will be considered to indicate severe depression. Current, active member of an organized weight loss program (e.g., Weight Watchers, TOPS). Current participant in another weight loss study or other clinical trials. Have a friend or family member who is currently participating or is planning to participate in this clinical trial. Patient reported: inability to walk for about 10 minutes without stopping, feeling of pain in chest when doing physical activity, feeling of pain in chest when not doing physical activity. Note: unless pain in chest in known to be related to upper gastrointestinal disorders such as gastroesophageal reflux disease or heartburn. Clinically significant cardiac rhythm disorder that requires either medical and/or surgical intervention (e.g., paroxysmal or chronic atrial fibrillation).

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: vBloc (Active Device)<br>The treatment group will receive a functional device that will deliver charge to the vagus nerve during the study period | Device: vBloc (Active Device)<br>* Active device will deliver vBloc Therapy<br>* Other names: Maestro® Rechargeable System;|
| Sham Comparator: Sham (Non-active Device)<br>The control group will receive a functional, but non-active device that will deliver no charge to the vagus nerve during the study period | Device: Sham (Non-active Device)<br>* Functional non-active control device will deliver no vBloc Therapy<br>* Other names: Maestro® Rechargeable System;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Subjects Experiencing Implant/Revision Procedure, Device or Therapy Related Serious Adverse Events (SAEs). | To demonstrate that the implant/revision procedure, device and therapy related serious adverse event rate in the vBloc group at 12 months post-implant is significantly lower than 15%. | 12 months | 
| Percentage of Excess Weight Loss (EWL) by Body Mass Index (BMI) Method. | Observe at least a 10% greater excess body weight loss (EWL) from randomization with the Maestro System after 12 months of vBloc Therapy compared to Sham by body mass index (BMI) method. (Body mass index is calculated by dividing body weight (kg) by body height (m) squared (BMI=kg/m2)). | 12 months | 
| Percentage Responder Rate in the Treatment Arm. | The second co-primary effectiveness endpoint was based on responder rates with the following two requirements: (i) at least 55% of vBloc subjects would achieve a %EWL of at least 20%; and (ii) at least 45% of vBloc subjects would achieve a %EWL of at least 25%. | 12 months | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Obesity, Bariatric surgery, Excess weight loss, Vagus nerve, Vagal blocking, vBloc Therapy