Minneapolis-based NightWare — maker of a smartwatch therapeutic for people with nightmare disorder and PTSD-driven nightmares — has received breakthrough therapy designation for its in-development product. In addition, the company is launching two new placebo-controlled randomized clinical trials for its digital intervention, one of which is being conducted within Department of Veterans Affairs hospitals.

“[Breakthrough status] is a really nice thing from our perspective because we have, internally, had a lot of discussions around the reasons why we thought this was a significant and important advance in medical technology,” Dr. Daniel Karlin, chief medical officer at NightWare, told MobiHealthNews. “We’re engaged with the agency in trying to generate a body of evidence that doesn’t just show efficacy, but shows efficacy versus sham, versus placebo … and we’re doing it quickly because among veterans with PTSD, there’s a suicide per hour. We believe that this may reduce suicide, so we have an obligation to get this to folks as fast as we can.”

NightWare’s product is an app for the Apple Watch that uses the device’s biometric sensors to monitor the sleeping wearer’s heart rate and movement, Karlin explained. Within just a night or two of sleep, the app’s machine learning component is trained to detect when the wearer is distressed by a nightmare. At this point the smartwatch vibrates to interrupt the wearer’s dreaming, but not enough to wake them up or disrupt their circadian sleep pattern.

“We’re not actually using [nightmares] as our endpoint — I mean, we’re asking questions about nightmares and obviously we help to reduce nightmares, but the endpoint we’re actually looking at is sleep quality,” he said. “If we’re waking someone up too much, we’re not going to make them better. So the goal really is not just to reduce nightmare, but to improve sleep.”

As a treatment for PTSD patients with nightmare disorder, Karlin and CEO Grady Hannah said that veterans are a substantial population that could benefit from the treatment. To this end, the company has been conducting open-label trials of the app with the VA, and will soon launch a new 240-participant blinded, randomized, placebo-controlled trial in Minnesota VA hospitals.

Should the therapy prove effective among this population, Karlin and Hannah noted that these hands-on trials with the VA will offer their company a clear initial path toward commercialization.

“By virtue of working with the VA and having the VA population be the ones who are most likely to benefit from this treatment, we’ve really smoothed the path toward prescription and distribution in the VA system,” Karlin said.

Still, only about 20% of PTSD diagnoses are the result of combat, Hannah said, so the company is also looking to serve providers, payers, support groups and other organizations whose members might be at risk of PTSD nightmares.

“Those with PTSD and nightmare disorder, they cause payers up to five times annually what an average member costs,” Hannah said. “Sleep has such a huge effect on people’s overall wellbeing that we want to run health economics analyses, because we believe that by [helping] people get the benefits of their sleep, other symptoms and other issues that they’re facing, especially as they relate to the payer, will improve.”

For these populations, NightWare has recently launched and is seeking participants for a second site-less trial of its therapeutic app. This study will look to enroll 400 individuals, and will be similarly randomized, blinded and controlled.

Karlin said that the study’s site-less design and primary endpoint of 28-day change will help the company quickly package any favorable results into a regulatory submission. Of course, now that its received the FDA’s breakthrough designation, Karlin said that the company will work to accelerate the process further should the data pan out.

“If the effect size is larger than what we anticipated, this can go much faster,” he said. “So we’ll do an interim analysis and take a look. Once we think that we have enough data that we think that we can go to FDA with statistically clinically significant results, we would take that interim analysis and use it to get a clearance.”

Maintaining this balance of speed and proven efficacy is important for Karlin and Hannah, both of whom adamantly refer to their product as a digital therapeutic. By working to build a body of efficacy data before submitting the product for approval as a medical therapy, the company hopes that its app will distinguish itself from other digital wellness products and eventually be prescribed to patients by their clinician.

“That’s a really critical distinction here. You can think of a thing like a nightmare detector and reducer as a wellness product, but … we want to be able to accurately claim that we’re treating a diagnosable medical condition, and at that point you need a regulator to say that you can do the thing you’re claiming to do,” Karlin said. “In a disease like PTSD where the illness is caused by a failure to forget and the brain’s usual forgetting mechanisms have been hijacked to make things worse, these folks don’t have anywhere to escape from the memory of their trauma. During the day they can have flashbacks and be hyper-aroused all day, and if they go to sleep they have to re-experience the trauma all night. There’s no place to go, and that accounts for the suicide rates in this population.

“So we’re making a very different claim from a health and wellness product. We’re really saying that we think that this product will reduce the morbidity and mortality of the illness that we’re treating.”