BEDFORDSHIRE, U.K.—Mologic Ltd. announced in early August a clinical trial to evaluate the company’s urine-based diagnostic, HeadsUp, in monitoring pulmonary exacerbation in cystic fibrosis (CF) patients. The study aims to identify five urinary biomarkers associated with the onset of pulmonary exacerbation in adults with CF. It will also validate the use of the novel point-of-care (POC) test for patient’s self-monitoring of their condition.
Gita Parekh, head of R&D at Mologic, tells DDNews, “The objective was to come up with a new way to help patients understand, monitor and control what’s going on in their vulnerable lungs, by means of simple, low-cost tests—a way of putting patients at the center of their own care and empowering them to take control. But how could this be done? Currently, there are no effective home monitoring tests that could get anywhere near to providing these benefits. This all seemed like a very distant target, but a break-through came when the Mologic team found clear biochemical cues in the urine of patients with CF, i.e. biomarkers. Mologic scientists have worked out which urinary biomarkers reflect the changes going on in the lungs as an exacerbation is building up.”
Patients will be recruited from the West Midlands Adult CF Centre in Birmingham, U.K., where they are under the care of the trial’s principal investigator, Dr. Edward Nash. As one of the largest CF units in the U.K., the center currently provides care for at least 360 adults with CF.
“This is a two-phase study, with each phase running for four months. In Phase 1, 40 subjects will be performing a number of daily tests as well as taking a daily urine sample, which will be sent to Mologic. In Phase 2, the patients will be performing the test at home on a daily basis,” explains Parekh. “The study will provide information about the usability of the test system as well as validating the selection of biomarkers.”
The test is based on regularly measuring five different biomarkers in urine and using an app-imbedded algorithm to convert data to a traffic light “RAG” result, indicating whether the patient is stable or in need of medical intervention. Analysis of the samples will confirm which of the 15 biomarkers identified are the key ones associated with the onset of pulmonary exacerbation.
“The results will be displayed as a Red, Amber, Green traffic light risk rating system: a red result indicates a risk of an exacerbation and that the individual should contact their doctor; amber indicates that there have been some changes, so the individual should re-test after 24 hours; and green indicates that the patient is stable, and the usual frequency of testing applies,” notes Parekh. “The frequency of testing will be determined following statistical analysis of data generated during the trial.”
“The five biomarkers need to be refined from a panel of 15. We have already shown that all 15 biomarkers change when symptoms are first seen, but we are looking to select a combination of five (or fewer) biomarkers that can predict the diagnosis of an exacerbation before the onset of symptoms. This combination will then be confirmed during the first phase of the clinical trial,” she says. “The biomarkers that are being evaluated are all known markers of inflammation, ranging from signaling molecules that recruit neutrophils to the inflammation site; degranulation molecules including proteases released by the neutrophils to fight off the infection that can become self-destructive; protease inhibitors that usually regulate the proteases (reduce the subsequent damage caused by the proteases in stable state) that are impaired, thus causing a further imbalance; and degradation molecules that are a consequence of the damage caused by the proteases to the lung structure, such as elastin and collagen. Other additional biomarkers we are looking at are contributed by the kidneys themselves, as a result of the downstream damage.”
Parekh commented that, “For people who suffer from a chronic lung disease such as CF, there is an ever-present risk of recurrent lung attacks (exacerbations) during which every breath can be a struggle. HeadsUp is non-invasive and allows frequent testing in the home, empowering patients to take control of their condition, which has the potential to reduce lung damage and avoid stays in hospital.
“This is the first time such a study has been set up that allows measurement of inflammation biomarkers on a daily basis from people with CF. It has never been deemed possible previously, as other sample types frequently used—such as blood, sputum and bronchoalveolar lavage fluid—are not samples that can be easily collected on a daily basis. The key to making it possible is the use of urine as the test sample. Samples can easily be collected, making it acceptable for frequent testing in the home, just like a simple pregnancy test.”
“To be able to analyze changes in the levels of the biomarkers allows us to fully understand the biomarker profiles building up to an exacerbation, which has only been possible in in-vitro studies until now. A next-generation test will be for pediatrics, which would be immensely valuable for the young children where symptoms are not so obvious to the child or the carer. Access to such a simple test will enable patients to understand, monitor and therefore control what’s going on in their lungs,” she concludes. “The ability to predict an exacerbation before symptoms are seen will allow appropriate action to be taken earlier, thereby potentially limiting its seriousness and impact. HeadsUp will provide a way of putting people with CF [and those who care for them] at the center of their own care, and empowering them to take control.”