Optimizing SNM: PEER trials investigate potential of SNM lead sensing

Clinicians currently determine the optimal program settings for sacral neuromodulation (SNM) for overactive bladder (OAB) by using motor and sensory responses. However, these evaluations are, to some degree, subjective measures, explains Colin M. Goudelocke, MD, a urologist at Ochsner Health Center in New Orleans, Louisiana.

Colin M. Goudelocke, MD

In the following interview, Goudelocke discusses the PEER trials, which are seeking to advance SNM by determining the efficacy of a closed-loop approach to therapy—a more responsive method where stimulation is guided by real-time feedback to treatment. These trials are exploring whether sacral evoked responses, or the electrical waveforms detected after nerve stimulation, can serve as biomarkers to optimize therapy and predict treatment success.

In the initial PEER trial, investigators showed that these waveforms could be detected at stimulation levels that were not uncomfortable for patients. Data from the PEER 2 trial, which were presented at the 2025 American Urological Association Annual Meeting in Las Vegas, Nevada, confirmed that these waveforms correlate well with traditional motor and sensory programming and may even be more sensitive.¹ Investigators are now investigating whether specific waveform patterns can predict better outcomes.

Ultimately, the goal is to use SNM lead sensing as a novel way to optimize SNM programming, which could revolutionize how OAB is treated.

Goudelocke reports relevant disclosures with Medtronic, Inc, who supports the PEER trials.

How do you approach patient selection for sacral neuromodulation?

As I'm sure a lot of people are aware, we've undergone a revolution of sorts in terms of the guidelines [for overactive bladder]. We were always thinking of things in terms of first-line therapy, second-line therapy, [and] third-line therapy. We would start off talking about behavioral changes like dietary modification or fluid moderation, maybe pelvic floor exercises and that sort of thing. [We could then] talk about concomitantly starting pharmacologic therapy and behavioral therapy, but we thought about pharmacologic therapy as second-line therapies. So, after we had tried to reduce your caffeine intake, then we would start these overactive bladder medications, either anti-muscarinics or beta-3 agonists later on. If we had tried multiple medications and exhausted all of that, then and only then we'd start to talk about what were called third-line therapies, or advanced therapies, like Botox injections into the bladder, tibial neuromodulation, percutaneous tibial neuromodulation, and of course, what we're talking about today, sacral neuromodulation.

Roughly a year ago, we came out with a new set of guidelines. In many ways, I think it was much more patient centric. It was more respectful of patients and their wishes. It [avoided] the hoops that [patients] have to jump through in order to get to a certain therapy. That can be very frustrating. If you're a woman who's urinating 15 times a day and getting up 4 times at night, and someone starts talking about moderation of your caffeine intake, that could be a very frustrating thing to undergo. Also, a lot of times, patients very quickly realized that they weren't having a proper response to pharmacologic therapy, or maybe they were having intolerable side effects. We also have to deal with the economic reality of medicine, which is that for a lot of patients, some overactive bladder medications can be costly out of pocket.

The guidelines now talk about a model in which we work with our patients. We discuss the options, whether it be pharmacologic therapy, behavioral therapy, tibial neuromodulation, sacral neuromodulation or botulinum toxin. [We discuss the] risks and benefits, and then we make a decision together.

To be honest, even in a shared-decision model, I would say most of my patients who are proceeding on to sacral neuromodulation have tried behavioral therapy. Most of the time they've tried at least some, and oftentimes several, pharmacologic therapy options, simply because I think in a shared decision-making model, the majority of patients are still going to say they’d like to try oral medication and behavioral changes before they do something that may be more invasive. So, even in a shared decision model, oftentimes those therapies do still fall into that first-line, second-line, third-line therapy model, but now it's an informed decision that the patient is making.

So, I think about sacral neuromodulation for any patient with overactive bladder who's interested in it, but realistically more often, patients who have tried other therapies, oftentimes pharmacologic therapies, non-surgical therapies, and either have had intolerable side effects, or they oftentimes have just not seen the improvement that they're hoping to see with a surgical therapy.

What questions are the PEER trials seeking to answer?

To really take a step back and take a 30,000 foot view, let's review how we deliver sacral neuromodulation. In sacral neuromodulation, we place a lead adjacent to typically the S3 nerve root, either on the right side or the left side, and we're stimulating that sacral nerve root in order to affect a neuromodulation, a change in the way that the nerve is functioning in how it conducts the overactive bladder signal. The way that we've administered sacral neuromodulation therapy for 30 years has been to just stimulate the nerve. We'll stimulate it at a given frequency and continuously do that.

When I first started doing this, we used to cycle on and off. We found that that was detrimental to battery life, so most people are not doing cycling anymore. But essentially, we just continuously and constitutively stimulate that nerve. There are some thoughts that continuous stimulation of the nerve, in theory may have some neuro-accommodative effects. One of the issues we see with neuromodulation in some patients, is that over time [the efficacy is weakened.] So, [patients may see a] robust therapeutic response right after we put that lead in, but now it's 6 weeks or 6 months or a year afterwards, and maybe they’re not doing as well anymore. It may simply be that by stimulating that nerve all the time in the same way, we run into some problems.

There's this idea in other types of therapy that I would call closed loop therapy. The analogy I think we frequently use is if I'm implanting an insulin pump in a patient with diabetes, we would never in a million years, think, "Well, I'm just going to release insulin into the body, and, we'll see what happens." Of course, not. What do we do? We release some insulin and then we see the resulting blood sugar. If the blood sugar is a little higher, then we'll release a little more insulin. If the blood sugar is a little lower, then we're going to release a little bit less insulin. Our therapy is responding to what the body is doing in response to that therapy. It's a closed loop.

If I'm putting in a pacemaker, I want to know what rhythm the is heart beating at in order to decide what pacing I’m going to do. I'm not just going to stimulate the heart. It's accepted in a lot of other therapies that we want to stimulate in response what's going on. Deep Brain Stimulation is another perfect example of that. The stimulation of the deep brain is in response to what the EEG is doing. That device is capable of both stimulating as well as sensing.

Medtronic, who is the sponsor of this study, does a lot of things in a lot of other areas. The company is making insulin pumps, they’re making deep brain stimulators. They're very intelligent physiologists and neurophysiologists that work in a lot of other areas saying, "We're doing this closed loop therapy in other areas. Is there a role for this in sacral neuromodulation?" That's the first reason why are we even thinking about this. It's logical to think, if this is a more effective therapy in other areas, is there a potential for it to be a more long-term efficacious therapy in sacral neuromodulation? That's the first question.

The second question that the PEER trials are trying to answer is: what are we responding to? There are a lot of different targets that you could respond to. Would we respond to a urodynamic parameter. Should we have continuous urodynamic evaluation? I don't know that that's very practical, but it certainly is a thought. It turns out that when you stimulate the sacral nerve root, you get what's called an evoked potential. What I mean by that is you're stimulating with a little electrical signal, and then if you listen a couple of a few milliseconds later, you hear what I would almost call an echo. It might be the nerve itself responding. It may be some of the motor activity of the muscles that are being innervated by this nerve. It might be a combination of the 2.

But essentially, after you stimulate the sacral nerve root, you'll get a sacral evoked response, essentially get an electrical wave pattern. The typical neuromodulation lead that we've been putting in for 30 years has 4 electrodes. We're typically using 2 of those 4 electrodes to stimulate, 1 being the negative and 1 being the positive. So, we have an anode and a cathode in bipolar stimulation. We're using 2 of our 4 electrodes, but that mean we're also not using 2 out of our 4 electrodes. What Medtronic developed was a system that would use 2 of the electrodes to stimulate, and then could use the other 2 quiescent electrodes as the sensing electrodes.

So, we need 2 electrodes to stimulate in bipolar stimulation, and we also need 2 electrodes to listen for that waveform, listen for that electrical signal. It just so happens we have an electrode that we've been putting in patients for 30 years that is capable of doing that. That's one of the more exciting things about the PEER trial, is that if we're able to demonstrate useful data from this sensing trial, and if we're able to develop implantable generators that are capable of doing both the stimulation and the sensing, I'm actually able to use that as a backwards compatible device. So, if I have a patient that I implanted 6 or 7 years ago with a InterStim 2 device, and now she's 7 years out and her generator or battery life is starting to get towards the end, and if I have an a new generator that is capable of both sensing and stimulating, I don't have to put a new lead in this patient. I don't have to take out my old functioning lead, which a lot of people are loathe to do. When I have that patient under some light sedation in the operating room, and I'm taking out her old battery and putting in a new battery, if this technology is developed in that way, I could put in the new the new generation generator, the new sensing generator, in with the old lead, even if that lead is 10 or 15 years old. I think that's really exciting.

So, that was the second question. If we're going to develop a closed loop system, what are we responding to? In this case, we're responding to a signal that the nerve is sending back to us in response to that stimulation.

What did previous data from the PEER 1 trial show?

If we go all the way back to the PEER 1 trial, [we know that this] has been done in sheep. So the question was, can we do the same thing in humans? The other thing is that it's a little harder for sheep to complain. Do we have to stimulate so high in these patients that it's uncomfortable for them? It's not going to be a very useful technology if it's uncomfortable, if we have to stimulate so high to hear that signal that the patient's in pain. The very first thing that we did was we wanted to find out if we could collect this data in humans instead of sheep, and if we could collect it in a way that was comfortable to patients.

So, we went ahead and did this as a single site trial. I implanted the first 21 patients in what was called the PEER trial. We put in a test lead during their staged testing. During a staged test, we have an external connection to that lead, and so that's exactly what we used. We hooked up the external connection and we got some information while the patient was asleep. Then in recovery, after the patient was awake, we slowly increased the stimulation until the point at each either the patient didn't feel it was tolerable, or until we got a signal that was usable. Thankfully, in all of those patients, we were able to get a usable signal at stimulation parameters that patients were comfortable with. I was quite surprised at that, that we found it in every patient. The PEER trial essentially told us that A) we can get this signal in human patients, and B) we can get this signal at levels of stimulation that are not so uncomfortable that patients are going to be complaining.

What did the PEER 2 trial assess?What were the key findings?

So, we knew we could get this signal, but who cares? What's the relevance of it? That's what the PEER 2 trial was. We collected data at 3 points. We collected data while patients were asleep in the operating room, largely motor data. Then patients would wake up in the recovery room, and we could connect the device again, and we'd collect more data with sensory. Then patients would return a third time, and we get programming data on them again. We had more of a longitudinal idea.

Again, this was a multi-center trial. I think we closed it at 90 patients, and these were not just in overactive bladder patients. We looked at this in both OAB and fecal incontinence as well as non-obstructive retention. We were able to look at the waveforms. The first thing that we wanted to know was, how do these waveforms compare to what we normally think of when we put leads in and how we program patients? Right now, we're programming patients either to motor, and that's typically only in the operating room, and typically when patients are awake, we're programming to sensory. What's this correlation?

Interestingly, we found that these waveforms correlated very well with where we found them in both sensory and motor. If anything, these were a little bit more sensitive than motor and more sensitive than sensory. But there was good correlation between those 2. We definitely think that it's a relevant signal.

The other thing that we're working on in these data, and I think we'll be able to talk about more in future publications, is are there particular waveforms that predict success with therapy? Ultimately, that's what we want to know. If we can distinguish between, say, waveform alpha and waveform delta, does waveform delta predict more successful stimulation than waveform alpha? If it does, then when a patient is in the operating room and I'm trying to figure out whether I have an optimized lead, I may not be optimizing it to motor anymore. I may not be optimizing it to a flick of the great toe, or a contraction of the bellows of the pelvic floor. I may not be optimizing my lead to a patient feeling a particular sensation in a particular place. Maybe I want to optimize my lead to waveform delta, which is an objective measure. We always think about motor and sensory as objective measures, but the patient is telling me where they feel it and when they feel it, or I’m determining when I think I see bellows or when I don't think I see bellows. There’s some subjectivity to our objective measures. But these sacral evoked responses, these waveforms, could be the ultimate objective measures. There's no such thing as waveform delta, but if waveform delta predicted more efficacious therapy, then I want to put my lead in until I get waveform delta.

What are the next steps for this research?

As a next step, if the device is capable of sensing when it's in waveform delta and when it's not, maybe the device could make adjustments to the therapy to try to keep you in waveform delta—that closed loop of neuromodulation. A lot of that is a long way off. I'm not trying to imply that that is coming out tomorrow. We still have a long way to go, I think, until we get that. But it gives you an idea about the excitement, first in the PEER trial, and then some of our initial excitement in the PEER 2 trial, just in terms of the possibilities for lead optimization and programming optimization, and even programming individualization to a patient throughout their journey.

REFERENCE:

1. Villegas G, Goudelocke C, Ruiz H, et al. SNM lead sensing: Sacral evoked responses across standard therapy programs. J Urol. 2025;213(5S):e1354. doi:10.1097/01.JU.0001110196.19418.44.09