First Clinical Test of Feasibility of Ultrasound to Reposition Kidney Stones
Principal Investigator:
Hunter Wessells, M.D.
Organization:
University of Washington
Kidney stones exert a major burden on the US healthcare system, causing pain, obstruction of the urinary tract, and loss of worker productivity. They are of particular concern in space flight, because microgravity, dehydration, and altered bone metabolism increase the risk of stone development A kidney stone can cause debilitating pain as it passes or worse, become obstructing, and leading to other complications. Thus, developing a non-invasive approach to mitigate against severe complications would be a major advance with potential broad clinical applications on earth.
Dr. Hunter Wessells and colleagues in the Department of Urology and Applied Physics Laboratory at the University of Washington are conducting a research project to determine whether medical ultrasound devices can be used to reposition kidney stones within the human urinary tract. The research team will assess the safety and feasibility through a pilot clinical trial involving 15 subjects undergoing evaluation and treatment of existing kidney stones. The goal of the study is to determine whether kidney stones can be moved within the kidney and what the patient experiences during the repositioning.
Technical Summary
The prevalence of kidney stone disease is increasing, and is estimated to affect nearly 9 percent of the US population. The majority of stones will pass spontaneously with time. However, nearly 30% of stones require surgery. The most common surgical approach is to break stones into smaller fragments that can then pass spontaneously. This is typically done with either extracorporeal shock wave lithotripsy (shockwave lithotripsy – shock waves are focused from outside the body) or ureteroscopy and laser lithotripsy (requiring a small endoscope to be placed into the bladder and then advanced into the ureter or kidney with energy delivered from a small Holmium laser).
Astronauts are at increased risk of stone development because of microgravity, dehydration, and altered bone metabolism associated with space flight as well as medications prescribed to mitigate visual impairment and intracranial pressure (VIIP). A stone can cause debilitating pain as it passes or worse, become obstructing, leading to urinary tract infection, sepsis, renal failure, and death. As described above, surgery is the only currently available technology to affect when the stone moves from the kidney or manipulate the stone once it has begun to move.
Our research group has developed a new, non-invasive technology using low intensity focused ultrasound to reposition kidney stones. This is essentially a conventional diagnostic ultrasound system that is also programmed with longer ultrasounds bursts to impart sufficient energy to physically move a stone. These are similar to pulses that may be used in elastography or acoustic radiation force imaging. Like conventional ultrasound, the probe is placed in contact with the patient's skin to image the stone. The same probe is then used to focus the ultrasound and apply a burst (a sequence of pulses) of acoustic force to push the stone. Brightness mode (B-mode) imaging is interleaved with the "pushing" pulses (Push-mode) to monitor stone movement. The Push can be applied to any location and any depth within the image. The user controls the burst amplitude. To control probe surface heating, and thus patient safety, the system is programmed to control when the user is allowed to conduct the next push.
It is the goal of our technology to move the stone fragments to a location within the kidney to improve their chance of passage, and thus reduce the occurrence of additional symptomatic events and retreatment. For example, the chance of passing a stone from the lower pole of the kidney is approximately 35%, while the chance of passing a stone in the mid pole is over 80%. There is currently no non-invasive technology to relocate or manipulate these residual fragments within the kidney to improve their chance of passage, though research efforts are underway at several centers of excellence to treat this difficult problem. Aside from the clearance of residual fragments from lithotripsy, this technology could potentially be used to manipulate an obstructing stone back into the kidney, circumventing the need for urgent surgery. Further, repositioning a stone prior to surgery could result in a more favorable location in order to better access the stone to successfully treat it.
In space, the system would be an application on the diagnostic ultrasound system with minimal or no additional upmass. It would provide an option to detect and help a stone pass or prevent a stone passing, where currently there is no option. Astronauts might be routinely screened and tiny stone expelled before creating complications. Alternatively if a stone becomes large and symptomatic, the stone might be respositioned back into the kidney to delay treatment until return to Earth.
The device has been extensively tested in phantom models and in porcine kidneys. We have presented our work in peer reviewed scientific meetings regionally, nationally, and internationally. We have demonstrated effectiveness and safety of stone relocation in a porcine model. Minimal to no injury might be expected given that the acoustic pressures and energies are just above diagnostic ultrasound and much lower than those used currently in shockwave lithotripsy. Based on a porcine injury model, this technology performs at levels about 1/6th of the threshold for renal injury.
This one year project will conduct a study under an investigational device exemption (IDE G130085) approved by the FDA. The study is a 15 patient feasibility study demonstrating our ability to move stones in humans and to assess for any pain or discomfort associated with the procedure. This will be a non-randomized, unblinded single center first in human feasibility study to be conducted at the University of Washington Medical Center.
Patients presenting to the University of Washington Medical Center Urology Clinic with a documented kidney stone on imaging will be screened for this study. Those who meet the study criteria and indicate initial willingness to participate to the clinical staff will be approached by research staff who will explain the study and obtain informed consent. For patients receiving only medical expulsion therapy (medications to help pass the stone without the need for surgical intervention), the investigative study will occur either on the same day as the clinic visit, or scheduled for a return visit. For the pre-surgery (Shockwave lithotripsy or Ureteroscopy) participants, the investigative study will occur on the same day (but prior to) the surgical procedure. For the postsurgery (Shockwave lithotripsy or Ureteroscopy) participants, the investigative study will occur at the 4-8 week routine follow-up visit. The subjects will receive imaging confirmation of a stone fragment as part of their routine care at that follow-up visit.
The primary goal of this study is to demonstrate our ability to reposition stones within the human kidney collecting system.
Secondary goals include:
a) establish if there is any discomfort associated with the procedure
b) demonstrate the ability to move the stone in a controlled direction
c) demonstrate the ability to move large (> 5 mm) and small stones (≤ 5 mm)
d) qualify and quantify the complications from the procedure.
Outcome measures:
The following metrics will be used as a measure of success for an individual study:
• By any measure, the stone moved more than 2 mm.
• The treatment procedure was tolerable to the patient • No complication requiring intervention beyond that typically experienced with routine care.
Earth Applications
One in 11 Americans have had stones. Most form more than one stone over time. Our goal is an office-based procedure to use ultrasound to image and treat these stones and thereby to avoid surgery and repeated x-ray monitoring. Some of the many applications of the novel technology may include relieving obstructing calculi, pre-positioning of stones for improved surgical outcomes, imaging confirmation of stone number and size, and respositioning small kidney stones of residual fragments to facilitate their passage. There is commercial and clinical interest in the technology as it has the potential to change the way stones are treated for many people.
