EMPOWER Clinical Trial: Vagal Blocking for Obesity Control

This is a randomized multi-center study being done to measure the ability of a new medical device, Maestro System, to safely reduce body weight over five years in people who are considered obese.

The Maestro System is a neuromodulation system that consists of implantable and external components.

Implantable components: two leads (one electrode each for the anterior and posterior intra-abdominal vagal nerve trunks) that are connected to an implantable neuroregulator.

External components: one programmable, battery-powered, ambulatory external controller connected via a small, flexible cable to a cutaneous transmit coil that is positioned externally over the neuroregulator. A clinician programmer that transmits information to the controller and uploads data from the controller.

All non-diabetic subjects will be randomized in a 2:1 allocation to therapy ON or therapy OFF groups. All type 2 diabetes mellitus subjects will be randomized in a 1:1 allocation to therapy ON or therapy OFF groups.

All subjects will receive blinded therapy through the 12-month follow-up visit. All subjects will participate in a medical weight management program.

Eligibility Criteria:
Inclusion criteria

1. Informed consent.
2. 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 condition. Co-morbid conditions may include one or more of the following:

   * Type 2 diabetes mellitus (note: type 2 diabetics are allowed at selected centers only, see Inclusion criterion #5)
   * 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
3. 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.
4. 18-65 years of age inclusive.
5. Type 2 diabetes mellitus subjects (at selected centers, limited to approximately 34 subjects) with:

   * Glycosylated hemoglobin (Hb A1c) 6.5 - 9 % inclusive at screening visit.
   * Onset: 10 years or less since initial diagnosis.
   * Stable treatment regimen: no change in oral hypoglycemic treatment regimen within past 3 months.
   * Currently not using insulin therapy, GLP-1 receptor agonists (e.g., exenatide), or DPP-4 inhibitors (e.g., sitagliptin) 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.
6. Failure to respond to supervised diet/exercise program(s) in which the subject was engaged for at least 6 months within the last five years.
7. Ability to complete all study visits and procedures.

Exclusion criteria

1. Concurrent chronic pancreatic disease.
2. History of Crohn's disease and/or ulcerative colitis.
3. History of bariatric surgery, fundoplication, gastric resection or major upper-abdominal surgery (acceptable surgeries include cholecystectomy, hysterectomy).
4. History of pulmonary embolism or blood coagulation disorders.
5. Clinically significant hiatal hernias known from subject's medical record as or determined by upper endoscopy prior to implant if they have not had one done during the previous 6 months that specifically reported on the presence or absence of hiatal hernia making reference to the Z-line and/or diaphragmatic notch, in order to rule out subjects with hiatal hernia that may require surgical repair (to support exclusion criterion #7).
6. Current portal hypertension and/or esophageal varices.
7. Intra-operative exclusion: hiatal hernia requiring surgical repair or extensive dissection at esophagogastric junction at time of surgery.
8. Treatment with weight-loss prescription drug therapy within the prior three months and the use of prescription drug therapy or the use over-the-counter weight loss preparations for the duration of the trial.
9. Smoking cessation within the prior six months.
10. Known genetic cause of obesity (e.g., Prader-Willi Syndrome).
11. Overall sustained reduction of more than 10% of body weight in the previous 12 months.
12. Physician-prescribed pre-operative diet with intent to lose weight prior to surgery (note: a) study subject may continue any personal diet they were on prior to study enrollment \[see exclusion criterion #24\] b) standardized EMPOWER weight management program to be initiated in all subjects at time of activation, approximately two weeks after implant)
13. Current type 1 diabetes mellitus (DM).
14. Current or recent history (within 12 months) of ongoing bulimia.
15. Current alterations in treatment for thyroid disorders (stable treatment regimen for prior three months acceptable).
16. Current alterations in treatment for epilepsy (stable treatment regimen for prior six months acceptable).
17. Current treatment for peptic ulcer disease (previous history acceptable).
18. Chronic (more than 4 weeks of daily use) treatment with narcotic analgesic drug regimens (treatment with non-steroidal anti-inflammatory drugs acceptable).
19. Current alterations in treatment regimens of anti-cholinergic drugs, including tricyclic antidepressants (stable treatment regimen for prior six months acceptable).
20. 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.
21. Presence of permanently implanted electrical powered medical device or implanted gastrointestinal device or prosthesis (e.g., pacemakers, implanted defibrillators, neurostimulators etc.).
22. Planned or contemplated use of Magnetic Resonance Imaging (MRI) or oncological radiation during the course of the trial.
23. Significant psychiatric disorders that, in the opinion of the investigator, may interfere with subject's ability to follow study procedures and/or instructions.
24. Current, active member of an organized weight loss program (e.g., Weight Watchers, TOPS).
25. Current participant in another weight loss study or other clinical trials.
26. Have a friend or family member who is currently participating or is planning to participate in this clinical trial.
27. 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.
28. Clinically significant cardiac rhythm disorder that requires either medical and/or surgical intervention (e.g., paroxysmal or chronic atrial fibrillation).