Development of novel Aquilo Heat Therapy Device to treat patients with PeripheralArtery Disease

The objective of this proposal is to develop a novel device to provide leg heat therapy (HT) for patients with symptomatic peripheral arterial disease (PAD). The current non-interventional standard of care for PAD is a 12 week program of supervised exercise therapy (SET). For patients this is often very painful as they are exercised

to the point of claudication and many elderly patients find it difficult or impossible to repeatedly travel to a treatment facility. Thus the majority of these patients remain untreated. Recently HT has been shown to be a promising therapy to treat PAD patients. A recent study demonstrated that an 8 week course of home HT was

both safe and effective - with improvement in walking performance similar to SET. Home HT was also found to be comfortable and compliance was the treatment program was very high. Presently, there is no system commercially available for HT therapy despite the fact that HT may prove to be an optimal therapy for PAD

patients since it can be delivered comfortably and at home. The Aquilo multi-disciplinary development team has the expertise, experience, and confidence to achieve our objective of clinical translation and commercialization of a competitive advanced technology to safely and effectively treat PAD, which will lead to an improved therapy

for PAD patients. The proprietary Aquilo HT system (U.S. Patent Application No. 63/215,129) consists of two principal components. The first component is a wearable lower body garment that has an outer shell that is closed with a zipper and houses 6 pneumatic chambers. Inside the garment is a water circulating pad to provide HT.

Temperature thermistors are attached to the water circulating pad in the region of the calf and the thigh of each leg. The second component is a console. The console houses a heater and two pumps – one to circulate heated water and a second that pumps air into the pneumatic chambers to keep the pads in gentle contact with the leg.

The console has a touch screen for simple one-touch full treatment operation by elderly PAD patients. Many important safety features are programmed including audible and visual alarms and system shut off if leg temperature is excessive, kink detection and a low water level warning. The console will also include a data

collection system. Rigor of prior research was demonstrated by development of prototype devices and proof-of- concept testing to define design specifications, evaluate function and performance, and identify engineering challenges and formulate solutions for new the Aquilo HT system. In this phase I project, we will (1) complete fabrication of the Aquilo HT system and confirm achievement of the

design specifications (Aim 1); (2) demonstrate system safety and function in a small cohort of patients over a 12 week treatment period (Aim 2). Successful demonstration of feasibility of the Aquilo HT system will include: (1) achieve design specifications, function, and performance metrics (Aim 1), and (2) demonstrate safety (no

skin injury or skin burn) and device reliability over 12 weeks of therapy in 6 PAD patients (Aim 2). Collectively, upon successful demonstration of meeting design benchmarks and study metrics (phase I), we will work to achieve a design freeze, complete verification and validation (V&V) testing in compliance with Good

Manufacturing Practices (GMP), then conduct pre-clinical testing in compliance with Good Laboratory Practices (GLP). Our engineering control documents and pre-clinical test data and analyses will be then used to support an application for a clinical trial in PAD patients. Our vision is to successfully translate the Aquilo HT system into

clinical practice and improve the outcome of PAD patients.