WO2020123797A1 - Vagus nerve ablation devices, systems, and methods - Google Patents

Abstract

A system for vagus nerve ablation. The system includes a flexible catheter comprising a proximal end and a distal end, a distal balloon configured to secure the distal end of the flexible catheter within a body lumen or cavity, a window proximate to the distal balloon in the direction of the proximal end of the flexible catheter, a side balloon configured to extend from a side of the flexible catheter opposite the window; and a high intensity focused ultrasound (HIFU) transducer configured to pass through and rotate within the flexible catheter to emit HIFU energy through the window.

Description

VAGUS NERVE ABLATION DEVICES, SYSTEMS, AND METHODS

RELATED CASES

[0001] This application claims priority to United States Provisional Application No. 62/780,051 filed on December 14, 2018, and titled“VAGUS NERVE ABLATION DEVICES, SYSTEMS, AND METHODS,” which is hereby incorporated by reference in its entirety.

BACKGROUND

[0002] The present disclosure relates generally to medical devices, and in particular, is directed to devices, systems, and methods for treating obesity.

BRIEF DESCRIPTION OF THE DRAWINGS

[0003] The written disclosure herein describes illustrative embodiments that are non-limiting and non-exhaustive. Reference is made to certain of such illustrative embodiments that are depicted in the figures, in which:

[0004] FIG. 1 illustrates an example table of BMI classifications.

[0005] FIG. 2 illustrates a diagram in accordance with one embodiment.

[0006] FIG. 3 illustrates a BMI reduction bar graphs in accordance with one embodiment.

[0007] FIG. 4 illustrates an HIFU vagus nerve ablation system in accordance with one embodiment.

[0008] FIG. 5 illustrates a flowchart of a method of ablating the vagus nerve using the HIFU vagus nerve ablation system of FIG. 4.

DETAILED DESCRIPTION

[0009] Obesity in the United States is common, serious, and costly, and its incidence is growing. More than 2 in 3 American adults are presently considered to be overweight or have obesity. The prevalence of obesity was 39.8% and affected about 93.3 million of U.S. adults in 2015-2016. Obesity-related conditions include heart disease, stroke, type 2 diabetes, degenerative orthopedic conditions and certain types of cancer that are some of the leading causes of preventable, premature death. The estimated annual medical cost of obesity in the United States was $147 billion in 2008 US dollars. A useful gauge of body weight is the body mass index (“BMI”) which is calculated by dividing an individual’s mass in kilograms by their height in meters squared. FIG. 1 shows an example table 100 of BMI of adults ages 20 and older, wherein the BMI is classified for normal weight, overweight, obesity (including extreme obesity), and extreme obesity.

[0010] FIG. 2 is a diagram 200 illustrating the course and distribution of the glossopharyngeal nerve 202, vagus nerve 204, and accessory nerve 206. The diagram 200 also illustrates the diaphragm 208 and stomach 210. The vagus nerve 204 extends through the jugular foramen, then passes into the carotid sheath between the internal carotid artery and the internal jugular vein down to the neck, chest, and abdomen, where it contributes to the innervation of the viscera, reaching all the way to the colon. The posterior trunk of the vagus nerve 204 is derived from the right vagus nerve which travels with the carotid sheath. Some fibers may be derived from the left vagus nerve as well. Besides giving some output to various organs, the vagus nerve 204 comprises between 80% and 90% of afferent nerves mostly conveying sensory information about the state of the body's organs to the central nervous system. Hunger is one of the sensations transmitted from the stomach to the central nervous system along the vagus nerve. The right vagus nerve gives rise to the posterior vagal trunk at the lower esophagus and enters the diaphragm through the esophageal hiatus.

[0011] Vagotomy is currently being researched as a less invasive alternative weight-loss procedure to gastric bypass surgery. The procedure curbs the feeling of hunger and is sometimes performed in conjunction with putting bands on patients' stomachs, resulting in an average of 43% of excess weight lost at six months with diet and exercise. In a six-month open-label trial involving three medical centers in Australia, Mexico, and Norway, vagus nerve blocking helped 31 obese participants lose an average of nearly 15 percent of their excess weight. As of 2008 a year-long 300-participant double-blind, phase II trial had begun.

[0012] The posterior trunk of the vagus nerve is derived from the right vagus nerve which travels with the carotid sheath. Some fibers may be derived from the left vagus nerve as well. In certain embodiments disclosed herein, a physician may utilize electrical impulses applied to the gastric mucosa and then monitor for these impulses carried along the right vagus nerve by placing a skin electrode over the right carotid pulse. By doing so, neuromodulation may be used to determine whether the physician is targeting the appropriate area in order to apply focused high-energy ultrasound to ablate the posterior limb of the vagus nerve where the esophagus meets the fundus of the stomach. Further, the application of this energy may be monitored through ultrasound guidance in an effort to avoid any ultrasound injury to the posterior esophageal wall.

[0013] Certain embodiments include an endoscopic tool with a distal balloon and a side window proximal to the distal balloon that allows ultrasound monitoring and the application of focused high-energy ultrasound energy. The distal balloon is useful for positioning the device correctly at the junction between the esophagus and gastric fundus. The device may then be rotated while electrical impulses are applied to the gastric mucosal. The impulses may be monitored through a skin electrode over the right carotid pulse. A sublethal dose of the focused ultrasound energy may be delivered just beyond the wall of the esophagus as seen on ultrasound. When the device is turned to the correct location and the ultrasound energy is delivered and there is a loss of transmission of the mucosal electrical impulses, the operator knows through neuromodulation that the device is on target to hit the posterior limb of the vagus nerve. A full lethal dose of the focused ultrasound energy to the nerve may then be delivered to heat the posterior branch of the vagus nerve causing nerve ablation. The nerve ablation may then affect the patient’s appetite and possibly the Ghrelin (the hunger hormone) levels, which may lead to weight loss. Two of the potential complications that could occur may be diarrhea and dumping syndrome.

[0014] "Percutaneous CT-Guided Cryovagotomy for the Management of Mild-to-Moderate Obesity: A Pilot Trial," was led by David Prologo, MD, an interventional radiologist with Emory University School of Medicine in Atlanta, Georgia. The study was presented at the Society of Interventional Radiology 2018 Annual Meeting. The study was composed of 10 patients with a BMI between 30 and 37 who underwent the procedure and were followed for 90 days. All patients reported decreased appetite and the overall average weight loss was 3.6% of initial body weight and an average decline of nearly 14% of the excess BMI. No procedure-related complications were reported, and there were no adverse events during the follow-up. This minimally invasive approach is intended to avoid more invasive surgery, including gastric bypass, gastric sleeve, and lap band. The more invasive, generally laparoscopic bariatric surgical procedures result in larger decreases in the BMI relative to cryoablation of the vagus nerve 204, as shown in the BMI reduction bar graphs 300 of FIG. 3.

[0015] Despite the fact that the investigators in this study reported no adverse events with the use of a cryoprobe to ablate the posterior trunk of the vagus nerve 204, still this involved the CT- guided insertion of a several mm wide probe through the back to the posterior cardia section of stomach. Such an insertion pathway could result in accidental perforation of the diaphragm and/or breach of the pleural cavity with possible pneumothorax. In addition, the reported approximately 3 mm ice ball at the tip of the Cryoprobe would have to be close enough to the posterior vagus nerve trunk to ablate this nerve and might result in cold injury (possibly even creating a small zone of necrosis within the distal esophagus or cardia of the stomach with associated perforation). This approach to vagus nerve 204 ablation would necessarily require a CT unit for guidance, the use of which would probably limit this technique to radiologists. Furthermore, certain anatomic abnormalities, such as hiatal hernia, may render this approach difficult or impossible.

[0016] High intensity focused ultrasound (HIFU) has been used in recent years, particularly with MR guidance, to precisely ablate small volumes of deep brain tissue using heat created by focused ultrasound energy. The thermal effects of focused ultrasound can also be used to induce neuromodulation. When brain tissue is raised to a slightly elevated temperature— lower than that required for thermal ablation— neural signals may be temporarily suppressed in that area. This technique can be used to confirm the target in the brain during neurological treatments (e.g. essential tremor) before delivering the therapeutic dose of ultrasound energy to create a permanent lesion.

[0017] The vagus nerve ablation devices, systems, and methods described in this disclosure incorporates multiple features that allow for accurate device positioning in the distal esophagus and gastric cardia, neuromodulation to determine if the posterior vagal trunk has been appropriately targeted, and finally the ability to deliver a full therapeutic dose of focused ultrasound energy to permanently ablate this neural trunk.

[0018] FIG. 4 illustrates an HIFU vagus nerve ablation system 400 that may comprise a flexible shaft 402 or catheter with a distal end 424 and a proximal end 426, an HIFU shaft 404 or catheter that is inserted into and disposed within the flexible shaft 402, a proximal balloon inflation port 406 disposed near a proximal end 426 of the flexible shaft 402, electrical wiring for intra-gastric electro-stimulation 408 accessible and disposed near the proximal end 426 of the flexible shaft 402, a side balloon 410, a distal balloon 412, a window 414, an electrostimulation surface 416, an electrostimulation surface 418, a probe 420, and a guide wire 422.

[0019] The flexible shaft 402 may be, for example, a 15-30 French (F) (outer diameter - O.D.) or 18-20F (O.D.) catheter structure that can be advanced under fluoroscopic guidance transorally or transnasally over the guide wire 422 or a catheter (with/without a guidewire) past the naso- and oropharynx into the esophagus and inferiorly into the stomach 210 where a 2-3 cm diameter highly compliant balloon (i.e., the distal balloon 412) is inflated with dilute contrast. The distal balloon 412 is configured to secure the distal end of the flexible shaft 402 within a body lumen or cavity when the distal balloon 412 is inflated. Inflation of the distal balloon 412 may apply back tension the HIFU vagus nerve ablation system 400. The inflated distal balloon 412 causes the distal end 424 of the HIFU vagus nerve ablation system 400 to be appropriately seated in the cardia as the inflated distal balloon 412 cannot pass proximal to the gastroesophageal junction. Immediately proximal/cephalad to the distal balloon 412, a side opening or window 414 is situated in the flexible shaft 402. The flexible shaft 402 may have a tubular structure. The window 414 serves as the location for a high intensity focused ultrasound (HIFU) transducer which can be rotated within the lumen of the flexible shaft 402 (e.g., using the HIFU shaft 404). The size of the window 414 affords an acoustic window for the transducer allowing its rotation and delivery of its focused ultrasound energy through an arc of 30-60 degrees without any alteration in the positioning of the flexible shaft 402.

[0020] The side balloon 410 may be disposed on the surface of the flexible shaft 402 proximal to the distal balloon 412 and on the surface opposite from the window 414. The side balloon 410 may have a smaller diameter than the distal balloon 412. The side balloon 410 once inflated in the distal esophagus, pushes the window 414 against the luminal surface of the esophagus, thus optimizing the delivery of focused ultrasound energy through the wall of the esophagus. The flexible shaft 402, once the distal balloon 412 is inflated and the HIFU vagus nerve ablation system 400 is pulled back until resistance is encountered, is rotated so that the window 414 (denoted by radiopaque borders) faces the right posterolateral lumen of the esophagus. In some embodiments, radiopaque markers are disposed along a perimeter of the window 414. The side balloon 410 opposite the window 414 is then inflated to stabilize the window 414 in this location, which is the approximate location of the posterior vagal trunk on the surface of the inferior esophagus. The HIFU transducer, is advanced through the tubular structure (e.g., using the HIFU shaft 404) until it reaches the window 414. The HIFU transducer would most likely require a gel like acoustic medium to convey its focused energy to the esophageal wall. The HIFU transducer would be set to have its ultrasound energy converge at a very shallow depth of only 3-5 mm to target and ablate the posterior vagal trunk, which runs along the posterolateral surface of the distal esophagus, while striving to avoid thermal injury to the esophagus itself. The application of the ultrasound energy may be monitored through ultrasound guidance in an effort to avoid any ultrasound injury to the posterior esophageal wall. In some embodiments, the HIFU transducer may be re-sterilizable and reusable.

[0021] A practitioner may be able to monitor the ablation of the vagus nerve 204 by monitoring impulses applied to the gastric mucosa. The gastric mucosa communicates with the right vagus nerve and the practitioner may apply electrical impulses to the gastric mucosa via the HIFU vagus nerve ablation system 400 to see if the electrical impulses are communicated to the vagus nerve to the CNS from the gastric mucosa. The electric impulses of variable frequency and amplitude may be applied to the gastric mucosa from the HIFU vagus nerve ablation system 400 either via electrodes (e.g., electrostimulation surfaces 416 418) attached to the surface of the distal balloon 412 balloon or the probe 420 protruding or extending away from the distal end 424. The probe 420 may be curved in a manner to ensure contact with the gastric mucosa. These electrical impulses would be conveyed cephalad via the vagus nerve 204 to the CNS. Since the afferent impulses of the posterior vagal trunk would travel to the right vagus nerve, anatomical approximated in the neck by the right carotid pulse, one would detect these neural signals by placing a skin electrode over the right cervical carotid pulse and observing these impulses on an electromyography (EMG) monitor. The thermal effects of focused ultrasound from the HIFU transducer rotated in a favorable therapeutic position can also be used to induce neuromodulation. When the posterior vagal trunk is raised to a slightly elevated temperature— lower than that required for thermal ablation— neural signals over the right carotid pulse would be temporarily suppressed. If this is observed for a particular transducer position, then the full therapeutic HIFU dosage would be delivered, thus permanently ablating the posterior trunk of the vagus nerve 204 where the esophagus meets the gastric fundus. The ablation of the nerve would affect the patient’s appetite and probably the level of the ghrelin hormone, which may lead to weight loss.

[0022] Cool water/saline may be delivered to the esophageal lumen during the full therapeutic energy delivery to help reduce the chance of thermal injury to the adjacent esophageal wall.

[0023] FIG. 5 illustrates a flowchart of a method 500 of ablating the vagus nerve 204 using the HIFU vagus nerve ablation system 400. S502 is advancing the HIFU vagus nerve ablation system 400 into an esophagus of a patient. The vagus nerve ablation system 400 may be advanced over the guide wire 422. The flexible shaft 402 may be advanced under fluoroscopic guidance transorally or transnassaly past the naso- and oropharynx into the esophagus and inferiorly into the stomach 210. [0024] S504 is inflating the distal balloon 412. The distal balloon 412 is configured to secure the distal end of the flexible shaft 402 within a body lumen or cavity when the distal balloon 412 is inflated. In some embodiments, inflation of the distal balloon 412 causes the distal end 424 of the vagus nerve ablation system 400 to be appropriately seated in the cardia. When the distal balloon 412 is inflated, the distal balloon 412 cannot pass proximal to the gastroesophageal junction. The distal balloon may be inflated with dilute contrast via the proximal balloon inflation port 406.

[0025] S506 is rotating the flexible shaft 402 so the window 414 faces the right posterolateral lumen of the esophagus. S508 is inflating the side balloon in order to push the window against the right posterolateral lumen of the esophagus.

[0026] S510 is transmitting high intensity focused ultrasound the HIFU transducer through the window 414 to target the posterior vagal trunk of the vagus nerve. The high intensity ultrasound energy may be converged at a shallow depth between 3 and 5 mm.

[0027] S512 is delivering electrical impulses of variable and frequency and amplitude to the gastric mucosa from one or more electrodes disposed on the vagus nerve ablation system 400. The electrodes may be found on the distal balloon 412 or on the probe 420.

[0028] S514 is placing a skin electrode over the right cervical carotid pulse. S516 is monitoring the impulses of the vagus nerve detected by the skin electrode by an electromyography (EMG) monitor.

[0029] S518 is delivering cool water or saline to the esophageal lumen during the full therapeutic energy delivery to help reduce the chance of thermal injury to the adjacent esophageal wall.

[0030] The advantages of this approach to vagus nerve ablation include its low invasiveness, short procedure times, optimizing the accuracy of energy delivery using neuromodulation, verification of successful neural ablation by EMG monitoring techniques, the requirement for only IV sedation, the need for only fluoroscopic guidance, rapid recovery, relatively low cost of materials, and outpatient basis. It can likely be performed on patients with a hiatal hernia. The performance of HIFU vagal nerve ablation would not preclude other bariatric procedures such as left gastric artery embolization.

[0031] Any methods disclosed herein include one or more steps or actions for performing the described method. The method steps and/or actions may be interchanged with one another. In other words, unless a specific order of steps or actions is required for proper operation of the embodiment, the order and/or use of specific steps and/or actions may be modified. Moreover, sub-routines or only a portion of a method described herein may be a separate method within the scope of this disclosure. Stated otherwise, some methods may include only a portion of the steps described in a more detailed method.

[0032] Reference throughout this specification to“an embodiment” or“the embodiment” means that a particular feature, structure, or characteristic described in connection with that embodiment is included in at least one embodiment. Thus, the quoted phrases, or variations thereof, as recited throughout this specification are not necessarily all referring to the same embodiment.

[0033] Similarly, it should be appreciated by one of skill in the art with the benefit of this disclosure that in the above description of embodiments, various features are sometimes grouped together in a single embodiment, figure, or description thereof for the purpose of streamlining the disclosure. This method of disclosure, however, is not to be interpreted as reflecting an intention that any claim requires more features than those expressly recited in that claim. Rather, as the following claims reflect, inventive aspects lie in a combination of fewer than all features of any single foregoing disclosed embodiment. Thus, the claims following this Detailed Description are hereby expressly incorporated into this Detailed Description, with each claim standing on its own as a separate embodiment. This disclosure includes all permutations of the independent claims with their dependent claims.

[0034] Recitation in the claims of the term“first” with respect to a feature or element does not necessarily imply the existence of a second or additional such feature or element. It will be apparent to those having skill in the art that changes may be made to the details of the above- described embodiments without departing from the underlying principles of the present disclosure.

Claims

CLAIMS What is claimed is:

1. A system for vagus nerve ablation, the system comprising:

a flexible catheter comprising a proximal end and a distal end;

a distal balloon configured to secure the distal end of the flexible catheter within a body lumen or cavity when the distal balloon is inflated;

a window proximate to the distal balloon in a direction of the proximal end of the flexible catheter;

a side balloon configured to extend from a side of the flexible catheter opposite the window; and

a high intensity focused ultrasound (HIFU) transducer configured to advance through and rotate within the flexible catheter to emit HIFU energy through the window.

2. The system of claim 1, wherein the HIFU transducer is configured to converge ultrasound energy through the window at a depth of 3-5 mm to ablate the vagus nerve.

3. The system of claim 1, further comprising a balloon inflation port toward the proximal end of the flexible catheter to inflate at least one of the distal balloon and the side balloon.

4. The system of claim 1, further comprising one or more electrodes to apply electrical impulses of variable frequency and amplitude to a gastric mucosa.

5. The system of claim 4, further comprising a skin electrode to detect the electrical impulses communicated through the vagus nerve.

6. The system of claim 4, wherein at least one of the one or more electrodes is located on the distal balloon.

7. The system of claim 4, further comprising a probe extending away from the flexible catheter near the distal end of the flexible catheter, wherein at least one of the one or more electrodes is located on the probe.

8. The system of claim 7, wherein the probe curves away from the flexible catheter in a manner to contact with the gastric mucosa.

9. The system of claim 4, further comprising electrical wiring accessible from the proximal end of the flexible catheter to communicate the electrical impulses to the one or more electrodes.

10. The system of claim 1, further comprising a shaft accessible from the proximal end of the flexible catheter to pass the HIFU transducer through the flexible catheter and to rotate the HIFU transducer relative to the window.

11. The system of claim 1, wherein radiopaque markers are disposed along a perimeter of the window.

12. The system of claim 1, wherein the window is sized to allow for focused ultrasound energy from the HIFU transducer through an arc of 30-60 degrees without alteration in a positioning of the flexible catheter.

13. A method for ablating a vagus nerve comprising:

advancing a vagus nerve ablation system into an esophagus of a patient, the vagus nerve ablation system comprising:

a flexible catheter comprising a proximal end and a distal end;

a distal balloon configured to secure the distal end of the flexible catheter within a body lumen or cavity when the distal balloon is inflated;

a window proximate to the distal balloon in a direction of the proximal end of the flexible catheter;

a side balloon configured to extend from a side of the flexible catheter opposite the window; and a high intensity focused ultrasound (HIFU) transducer configured to pass through and rotate within the flexible catheter to emit HIFU energy through the window;

inflating the distal balloon to place the distal end of the flexible catheter in a cardia of the patient;

rotating the flexible catheter so the window faces a right posterolateral lumen of the esophagus;

inflating the side balloon to push the window against the right posterolateral lumen of the esophagus; and

transmitting high intensity focused ultrasound from the HIFU transducer through the window to target a posterior vagal trunk of the vagus nerve.

14. The method of claim 13, further comprising delivering electrical impulses of variable frequency and amplitude to a gastric mucosa from one or more electrodes disposed on the vagus nerve ablation system.

15. The method of claim 14, wherein at least one of the one or more electrodes is located on the distal balloon.

16. The method of claim 14, wherein the vagus nerve ablation system further comprises a probe extending away from the flexible catheter near the distal end of the flexible catheter, wherein at least one of the one or more electrodes is located on the probe.

17. The method of claim 13, further comprising placing a skin electrode over a right cervical carotid pulse.

18. The method of claim 17, further comprising monitoring impulses detected by the skin electrode on an electromyography (EMG) monitor.

19. The method of claim 13, further comprising delivery cool water or saline to a lumen of the esophagus during a procedure.