Clinical trial of a novel treatment for peripheral arterial disease

Peripheral arterial disease (PAD) is a debilitating condition prevalent in people over 70. 

The symptoms involve leg pain after exercise and in severe cases pain at rest, ulcers and gangrene. 25% of people with severe disease need a leg amputation within a year. 

The current treatment options are limited and often ineffective. PAD occurs in patients with a build up of cholesterol in their blood vessels, with resulting poor blood flow to the lower limbs. 

Nitric oxide (NO), generated from the inner lining of blood vessels, is a key molecule in protecting arteries from PAD. NO is impaired in PAD and we have identified a protective pathway involving stimulation of a molecule called the beta 3 adrenergic receptor (ß3AR). 

By stimulating the ß3AR we have found that blood flow to the limbs is substantially improved in a pre-clinical model of PAD. We now aim to test the effect of a similar drug in humans. 

In this pilot clinical trial, we will test the effectiveness in PAD of Mirabegron, a ß3AR stimulator, that is safe and tolerated in humans for unrelated diseases. 

We hypothesise that patients receiving Mirabegron will show improvement in their exercise ability (peak walk time) over 3 months compared with placebo controls. 

This pilot study will inform the design of a larger, multi-centre study, and assist us in applying for the larger funding required. 

ß3AR stimulators may prove an improved and imminently translatable treatment for sufferers of PAD.