Our journey with U-RHYTHM began in 2021 when Dr Thomas Upton, Clinical Research Fellow, updated us on the development of a prototype wearable device to extract hormones, including cortisol levels, in the body over the full 24 hours. The device has the potential to provide both our patient community and the doctors looking after us with important information about cortisol levels over the day and how our replacement therapy can be improved by changes in both dose and timing of treatment.
There has been research over the years, into how doctors can improve cortisol replacement, including new pump therapies and sustained or delayed release preparations of cortisol. But it has been difficult to find a way to measure the effects of these treatments on body levels of cortisol and whether they improve on the current standard treatment. Many of our community feel frustrated that, despite feeling unwell on their current treatment, there is no way to tell whether their hormone levels are normal over the day.
U-RHYTHM aims to provide the solution to this problem.
2021: The Research Facts:
Disease: Addison’s disease and other diseases affecting the adrenal gland including Cushing’s syndrome and primary aldosteronism.
Research Team: Our research has been conducted as part of a Horizon 2020 EU project called ULTRADIAN. This project brings together multiple centres including experts in Addison’s disease in Bristol and the Karolinska Institute in Stockholm.
Organisations: University of Bristol, Karolinska Institute, University of Bergen, Evangelismos Hospital Athens, DesignWorks Windsor.
Timeline: 2016 - ongoing
What are the aims of this research?
We have been using the portable sampling system called U-RHYTHM to profile hormones over 24 hours in people as they go about normal activities. We have several aims. Importantly, we want to describe and characterise the normal healthy variation in adrenal hormones (including cortisol) across people of different ages. Alongside this, we have also sampled patients with endocrine conditions, including Addison’s disease. Using all this information, we want to both improve the diagnosis and management of endocrine diseases affecting the adrenal gland.
Why is this research important?
In health, adrenal hormones are secreted in pulses and have complex rhythms that vary across the day. However, this complexity means that measuring a hormone at just one time point tells you very little, can delay diagnosis, or simply be very difficult to interpret. Using U-RHYTHM, we can measure 72 times per day, including during sleep, to obtain a very detailed picture of hormone dynamics.
When we think about a condition like Addison’s disease, hormones are not replaced in a pulsatile manner; rather, most people take a tablet just 2-3 per day. This means that there are likely to be times of the day when hormone levels are much higher or lower than you would find in person, with normal adrenal function, and normal rhythms of hormones are not replicated.
We believe that in the long-term better hormone replacement modalities are needed for Addison’s disease and U-RHYTHM provides a tool to assist with that."
How will findings benefit people with Addison’s disease and adrenal insufficiency?
By comparing the observed profiles in Addison’s disease with profiles of healthy normal variation, we will be able to quantify for the first time the important differences in cortisol exposure during normal daily life. Rather than generic standard dosing of oral medication, we aim to be able to optimise therapy to best represent healthy physiology and the needs of the individual. In the future, U-RHYTHM sampling technology could be used to monitor and optimise hydrocortisone pump therapy to recreate pulsatile secretion of hydrocortisone across the day and night.
What are your timelines on the project?
We began recruitment in mid-2017 and the last participant was recruited in Bristol in early March 2020, just prior to the pandemic. The COVID outbreak has unfortunately caused some delays in our work, but we hope to publish the healthy volunteer results later in 2021, followed by the release of the results from the Addison’s cohort and other patient groups. We are actively seeking further grant funding to continue our research.
A key priority is to finish the analysis of the ULTRADIAN project and get the results published in academic journals. We have many plans and ideas about how U-RHYTHM could be used to help understand and treat medical conditions and some of those projects are already underway!
2023 Updates following the results from the Clinical Study
Dr Thomas Upton updates us on U-RHYTHM, now described as a 'world first' and a 'revolution in hormone understanding'. The ability of U-RHYTHM to perform continuous hormone sampling, whether at work, with friends and family, or even during sleep, means that we can get a better understanding of what normal hormone physiology is and use this information to inform hormone replacement in the future, or to diagnose endocrine disease.
Research link: High-resolution daily profiles of tissue adrenal steroids by portable automated collection – Science Translational Medicine Volume 15 Issue 701 - 21 June 2023
Journal of Internal Medicine: Circadian and ultradian rhythms: Clinical implications
How does U-RHYTHM work?
We use a technique called microdialysis, which works by allowing hormones to diffuse across a small membrane placed just below the surface of the skin. The fluid containing the hormones is stored in the U-RHYTHM portable device, which is later sent off for analysis. During the sampling process, participants can continue most normal activities at home – the device samples automatically, requiring no input from the wearer. We explain more in our video linked at the end of this article.
Hormone systems work dynamically – that is, concentrations of hormones change throughout the day. This is due to multiple factors, including intrinsic or internal rhythms (the circadian rhythm is a good example) and also responsiveness to the environment and the consequences of behaviour.
Traditional measurements of hormone systems typically rely on single time points or integrated measures, which cannot give much or any information about dynamics.
Furthermore, really important changes occur during the night – a time that is almost inaccessible to measure except during hospitalization. Our research is important because it reveals insights to the importance of rhythms and dynamics, including reasons for variability that occurs between people.
We think our research will benefit people with adrenal insufficiency by providing vital information about how to improve glucocorticoid replacement by making it more personalised and physiological. Additionally, such understanding could lead to the development of technologies for potential real-time feedback about cortisol dosing."
Where did the name U-RHYTHM come from?
The name emerged during discussions amongst the ULTRADIAN partners. It sounds a bit like ‘your rhythm’, alluding to the personal kind of information that it provides.
What are the next steps?
Right now, we are collating and preparing data on our Addison’s, Cushing’s and primary aldosteronism patients. We hope to be able to do more follow-up studies in people with adrenal insufficiency in the near future.
The U-RHYTHM devices are now being sold to the rest of the research community by the University of Bristol spin-out company, Dynamic-Therapeutics. We want this research and device to help other conditions, so please get in touch.
Does this work mean that something like a cortisol sensor could be available in the future, similar to 'at-home' glucose monitors for diabetes?
That could definitely be possible – although there is still a way to go before that would be available! The continuous glucose monitor (CGM) analogy is a good one and has revolutionized how people manage diabetes. Hopefully, we will have a similar kind of technology for managing adrenal insufficiency in the, not too distant, future.
Tell us more about public interest in the project. Does this help the development of the research?
Our work has generated a lot of interest both from research and patient communities. It's really important that we share our work and get feedback from patient advocacy groups such as the ADSHG, who provide vital context for our research – and who we hope ultimately will be the beneficiaries of our findings.
You can read the BBC article online: Device developed in Bristol offers 'revolution' in hormone understanding.
How can we support this research?
Please follow our social media threads, and contact us if you have any questions or suggestions! While we don’t have any active studies recruiting adrenal insufficient patients right now, we hope to do some in the future and it would be great to see you involved.
Use the power of social media and comment on the Journal of Internal Medicine's Instagram and/or Facebook post about the device to show there is a demand for this new device for our rare disease!If you're a researcher or scientist and think this research may help your work, please get in touch with us via Dynamic-Therapeutics.
When will people with Addison's and adrenal insufficiency be able to access the device?
We’d love to have a simple answer to this, but more research studies and funding is needed. However, the U-RHYTHM devices are being used and sold to the research community by the University of Bristol spin-out company Dynamic-Therapeutics.
Right now we are collating and preparing data, and more follow-up studies are required before the device can be certified and made more freely available as a clinical tool. Further use in the NHS will also be dependent on local funding decisions. These will be sensitive to patient support group pressure, which is why ADSHG community support is so valuable! We would need a crystal ball to give an accurate answer but rest assured we’re doing all we can to make it happen.
If you're a researcher or scientist and think this research may help your work, please get in touch with Dynamic Therapeutics on: info@dynamic-tx.co
Professor Stafford Lightman and Dr Thomas Upton explain how U-rhythm works
You can follow Dr Upton on X: @HotmasUpton
U-RHYTHM devices are now being sold to the rest of the research community by the University of Bristol spin-out company Dynamic-Therapeutics. We want this research and device to help other conditions, so please get in touch.
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Suzanne's story: participating in the 2021 ULTRADIAN research trial, testing U-RHYTHM