Deep Brain Stimulation Effects in Patients With Chronic Refractory Obesity

This is a pilot study to evaluate the safety and efficacy of deep brain stimulation (DBS) of the lateral hypothalamic area (LHA) as a treatment for chronic refractory obesity. This study will include 6 individuals with chronic refractory obesity, that have failed other treatments including gastric bypass surgery.

Six (N = 6) subjects with chronic refractory obesity will receive bilateral DBS implants in the LHA using the Boston Scientific Vercise Gevia DBS system. The primary objective is to evaluate the safety of DBS of the LHA using the current-driven Boston Scientific device and compare that to the safety data for our previous pilot using the voltage-driven DBS system for the treatment of chronic refractory obesity. The primary efficacy objective is to determine if DBS of the LHA can affect energy balance (i.e. energy intake and/or energy expenditure) in these patients. Secondary outcomes include quality of life outcomes and changes in feeding behaviors. Study participants will undergo a two-part DBS implantation procedure for placement of DBS electrodes in the LHA. Following this procedure, subjects with complete resting metabolic rate (RMR) testing to determine the optimal settings for the LHA stimulation. If effective, DBS technology might offer severely obese adults (BMI of ≥50 kg/m2), who have failed traditional therapy, a non-destructive, adaptable, reversible neurosurgical option for altering eating habits leading to sustained weight loss in the long-term.

Eligibility Criteria:
Inclusion Criteria:

1. Male and female patients age ≥ 22 years and \< 65 years old with a BMI of ≥ 40 kg/m2.
2. Failure of bariatric surgery (gastric bypass) and subjects who have no endoscopically or surgically correctable causes for failed bariatric surgery. "Failed bariatric surgery" is determined using the modified Reinhold classification as patients who are currently more than 50% over ideal body weight at least 24 months after a technically successful surgery (as confirmed by a esophagogastroduodenoscopy (EGD) within the 6 months prior to ICF).
3. Stable at their present weight (+/- 3 kg) for a 12-month period.
4. Neuropsychiatric evaluation must not reveal any issues that will be an impediment to subject's participation (as listed in Exclusion Criteria 2, 3 and 4).
5. Karnofsky Performance Score \>60.
6. Platelet count \>125,000 per cubic mm.
7. Prothrombin time (PT) and partial thromboplastin time (PTT) within normal limits.

Exclusion Criteria:

1. Any intracranial abnormality or medical condition that would contraindicate DBS surgery.
2. Have a history that includes a prior suicide attempt.
3. Have any significant psychiatric condition likely to compromise the subject's ability to comply with requirements of the study protocol (e.g. bipolar, schizophrenia, mood disorder with psychotic features, cluster B personality disorders) or have any prior history of schizophrenia or bipolar disorder or active psychotic episodes.
4. Have a current diagnosis of major depressive episode per DSM-IV (Diagnostics and Statistical Manual of Mental Disorders) criteria or has a current BDI-II score ≥ 17.
5. Any current drug or alcohol abuse, per DSM-IV criteria or any history of substance abuse (alcohol or other drug) or dependence during the past 12 months.
6. Any history of recurrent or unprovoked seizures.
7. Any history of hemorrhagic stroke.
8. Any diagnosis of acute myocardial infarction or cardiac arrest within previous 6 months.
9. Any diagnosis of a neurological disorder, such as multiple sclerosis, stroke, Parkinson's disease, severe brain atrophy or the presence of subdural hygromas or subdural hematomas.
10. Any history of hypothyroidism.
11. Any history of demonstrated binge eating.
12. Concurrent use of weight-loss prescription drug therapy or the use of over-the-counter weight loss preparations.
13. Any prior intracranial surgery or device implantation.
14. Any other active implanted devices (e.g., spinal cord stimulator, cochlear implant, pacemaker, vagus nerve stimulator) and /or drug delivery pumps, whether turned on or off. Passive implants (e.g., knee prostheses) would be allowed provided that they would not interfere with the DBS.
15. Any previously implanted Vagus Nerve Stimulation (VNS) patients.
16. A condition requiring or likely to require the use of Magnetic Resonance Imaging (MRI), diathermy or electroconvulsive therapy (ECT).
17. Likely to require the use of monopolar cautery, radio-frequency (RF) procedures, external defibrillation, lithotripsy, radiation therapy or transcranial stimulation.
18. Currently on any anticoagulant medications that cannot be discontinued during perioperative period.
19. Have any significant medical condition that is likely to interfere with study procedures or likely to confound evaluation of study endpoints, (e.g. hepatitis or HIV).
20. Any terminal illness with life expectancy of \< 1 year.
21. Any diagnosis of malignancy (except basal cell of skin) within the past five years.
22. Any unresolved infection, a coagulopathy or significant cardiac or other medical risk factor for surgery.
23. Current or future risk of being immunocompromised (due to medications, disease factors, illness, etc.) that might significantly increase risk of infection.
24. Participation in any other clinical trial (e.g. drug, device, or biologics) concurrently or within the preceding 30 days. Participation in any other study will be allowed per investigator/sponsor discretion only.
25. Plan to receive any procedure that involves sudden jerking motions of the head or neck (e.g. certain chiropractic therapies) or massage and manipulation directly over the leads in the scalp, neck or chest, at any time during the study.
26. A female who is breastfeeding or of child-bearing potential with a positive urine pregnancy test or not using adequate contraception.
27. Not able to speak, write and read in English language as determined by the investigator.
28. Overall intellectual abilities below a standard score of 80 based on results from the Wechsler Abbreviated Scale of Intelligence (WASI; Wechsler, 1999)
29. Unable to fit into MRI or CT (Maximum weight limit is 180 kg (396 lb.).
30. Plasma pre-albumin \< 14 mg/dL
31. Obesity as part of another medical condition, neurological injury or lesions, related to medication side effect, or as part of a genetic syndrome (i.e. Prader-Willi Syndrome, Leptin deficiency, etc.)
32. Be eligible for bariatric surgery revision including gastric outlet exclusion, gastrogastric fistula or other reasons that would qualify for a revision of their gastric bypass
33. Unable or unwilling to follow up for scheduled clinic visits