The SPHINX study

As a first year rheumatology registrar, Dr Mandana Nikpour cared for a young woman with severe lupus.

D4D_5526 copyDespite the best efforts of Dr Nikpour and her team, the patient died, leaving a five-year-old son without a mother. Dr Nikpour found this experience very distressing, inspiring her to dedicate her career to helping patients with debilitating autoimmune diseases such as lupus and scleroderma.

After completing her PhD in epidemiology and biostatistics at University of Toronto, Dr Nikpour has been able to combine her passion for her patients with a love of numbers as a clinician researcher.

Dr Nikpour is leading the Australian Scleroderma Cohort Study (ASCS), a multi-centre nationwide collaboration across all disciplines in 13 centres around Australia. The study is ongoing, collecting data on 1500 patients, placing the study amongst the largest worldwide.

‘Scleroderma is a multi-organ disease, notable for both the morbidity and mortality it inflicts in patients. Even though it’s rare, it packs a mean punch. What it lacks in frequency, it makes up for in the impact it has on a patient’s life,’ Dr Nikpour says.

One of the hallmarks is thickening of the skin through fibrous tissue, which begins in the periphery of the hands and feet, before moving into the arms and legs and impairing function.

The two major causes of mortality are heart and lung complications, in particular Interstitial Lung Disease (ILD), a scarring of the lungs similar to that of the skin, and Pulmonary Arterial Hypertension (PAH), an increased pressure in the vasculature of the lungs which puts a lot of strain on the heart.

‘Despite all current therapies, the median survival of PAH is three to four years. Prior to using these advanced therapies, median survival was only around one and a half years.’

The success of ASCS has allowed Dr Nikpour and her team to secure a major NHMRC grant for a clinical trial looking at a highly contentious area in the treatment of scleroderma, anticoagulation.

‘If you look at lung biopsies, you can see that the blood vessels are constricted, with the walls much thicker than normal. Within these tiny vessels right at the periphery of the lungs are tiny blood clots.’

‘Advanced therapies target the thickening of these vessels, but none address the clotting. Over the years, some physicians have chosen to thin the blood, while others have chosen not to due to potential side effects.’

‘Using data from the ASCS we were able to conduct an observational study, which saw that even when you adjust for other factors, those who happen to be anti–coagulated at physician discretion had better survival.’

‘The ACS has generated a very important hypothesis for developing a clinical trial. From this preliminary data we were able to make a case that this issue needed resolution and that the only way to do so is through a randomised controlled trial.’

The SPHINX study, as it is known, is a five year study, with the end point being a composite of clinical worsening and mortality. It will be the first multi-centre trial in anticoagulation in scleroderma ever.

‘We have now started recruiting and ensuring ethics and regulatory approvals are in place. We are well under way in all sites across Australia.’

‘The use of anti-coagulants has been acknowledged as high priority for addressing. This study is a unique one in that a positive or negative outcome will be very informative.’

In addition to securing sizeable NHMRC program funding, Dr Nikpour also received an Early Career Fellowship grant from the NHMRC, which allows her to continue her research in scleroderma, looking at risk actors and early diagnosis of PAH.

‘This funding allows me to continue looking at risk factors and predictors of risk factors with the hope of improving early diagnosis of PAH. PAH can be silent for a long time, by the time patients get breathless they are already suffering from severe hypertension.

Early diagnosis is the key.’

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