Previous Partnerships
Pathway of Clinical Care in Neurofibromatosis Type 1
Anonymous mixed-methods NHS service evaluation
Neurofibromatosis type 1 (NF1) is a rare genetic condition that causes tumours to grow along nerves. The tumours are usually non-cancerous, but can cause severe complications, pain, and significantly impact quality of life. About half of those affected also experience learning and behavioural difficulties. Early diagnosis is key to appropriately monitor the condition, allowing timely screening and intervention. Although the NHS provides two specialised Complex NF1 clinics, there is no standardised care pathway and limited non-specialised support.
Childhood Tumour Trust are keen to address the lack of ‘joined up care’. As a first step, in agreement with the NHS England Highly Specialised Service commissioners, we conducted an anonymous service evaluation. We co-produced two surveys with healthcare providers, Tumour Support Scotland, and Childhood Tumor Foundation to document diagnostic and clinical experiences from both patient and clinician perspectives. We were blown away with nearly 1100 responses from across the UK! Unfortunately the surveys revealed more than 50% of patients and families are not satisfied with the current NF1 care pathway. There is a need to standardise guidelines, improve awareness in healthcare professionals, and offer better coordinated care. We were able to present our findings at two British Paediatric Neurology Association conferences (posters downloads: 2023 and 2024), and are now working on our manuscript.
UNRAVEL
Understanding the genetics of ring chromosome 20 syndrome
Ring chromosome 20 syndrome (r(20)) is an ultra-rare and under-diagnosed condition associated with hard-to-treat epilepsy, learning and behavioural difficulties. Many people with r(20) wait years for their diagnosis because the ring formation is difficult to detect using standard genetic assessments. To address this issue, Ring 20 Research and Support UK have joined forces with researchers at Glasgow’s Royal Hospital for Children and biotech company Illumina Inc for their new UNRAVEL study. We helped them create a new ‘Ring Cohort’ within the NIHR BioResource to facilitate collection and transfer of blood samples from patients already diagnosed with r(20). Illumina will complete whole genome sequencing on the samples to learn more about the ring chromosome formation, and hopefully lead the way to better diagnostic tools. You can learn more about UNRAVEL here.
LiFE
A patient-led assessment of chronic fatigue in lipodystrophy using fatigue evaluations
Lipodystrophies are a group of rare genetic or acquired disorders where the body is unable to produce and maintain healthy fat tissue. Lipodystrophy UK contacted the PLRH with a ‘top 10’ list of research priorities in July 2016. We worked with the patient membership to refine their questions, and teamed up with medical experts from the National Severe Insulin Resistance Service and Newcastle Centre for Fatigue Research. Together we developed a research proposal investigating chronic daytime fatigue, as unfortunately many patients feel their fatigue is not diagnosed or treated properly, despite its severe impact on quality of life.
We originally secured funding to create a patient registry and research database, but after further consultation with the patient membership, we decided to streamline the database, use standardised questionnaires, and include a subset of participant interviews. We were awarded new funding from Addenbrooke’s Charitable Trust in 2020, but unfortunately Lipodystrophy UK were unable to commit to the lifespan of the project, and decided to defer. We look forward to exploring this again in the future.
My Sjögren's Diary
A secure patient database to track Sjögren’s Syndrome symptoms and support research
The Cambridgeshire regional support group for the British Sjögren’s Syndrome Association (Sjögren’s Cambridgeshire) is very interested in a wide range of research topics. Together, after consulting with rheumatologists and other patient groups, we decided the best way to serve their ambitions would be to create an online patient portal: My Sjögren’s Diary.
The Diary is a safe, secure and encrypted website, enabling anyone with Sjögren’s Syndrome to interact with their own health data. Participants can list their symptoms and medications and track them over time. Participants may wish to share this information with healthcare providers, to show how symptoms react to changes in lifestyle or new treatments. Participants with primary Sjögren’s Syndrome can choose to sync their data with the UK Primary Sjögren’s Syndrome Registry, which is available for approved research studies.
We secured a 2018 Research Award from the British Sjögren’s Syndrome Association, and developed the Diary with Sjögren’s Cambridgeshire, database programmers and rheumatologists. It is now led by Prof Wan-Fai Ng at Newcastle University. We dedicate this work to Carol Burns, co-founder of Sjögren’s Cambridgeshire, and driver of this project. Carol very sadly passed away in 2020, and is dearly missed.
Long-Term Lithium Use and Chronic Kidney Disease
Bipolar disorder is a severe psychiatric disorder requiring life-long management, often spanning decades with onset in adolescence or early adulthood. Lithium can be an effective treatment to stabilise mood, but is associated with tubular and glomerular kidney damage. Approximately 30% of patients taking lithium long-term will be diagnosed with early stage chronic kidney disease (CKD). Patients are generally advised to discontinue lithium if CKD stage 3 is reached, but there are very few resources available to inform this decision.
Cambridgeshire and Peterborough NHS Foundation Trust (CPFT) service users want to learn more about the implications of long-term lithium use. We approached Dr Rudolf Cardinal and his team at CPFT to help us analyse a preliminary dataset (lithium and kidney test results) from Addenbrooke’s Hospital. This proved very interesting, so Dr Cardinal successfully applied for a larger anonymised dataset. Although the team are still working on this analysis, the idea has inspired multiple tangential projects, including findings that suggest lithium use may reduce the risk of dementia (publication here).
EASE-PKD
Evaluating chronic pain in ADPKD using a patient-centred approach to data collection and synthesis: a national prospective observational study
Following the success with DRINK, PKD Charity submitted a second proposal to the PLRH, focusing on chronic pain interventions in autosomal dominant polycystic kidney disease (ADPKD). Chronic pain affects 60% of ADPKD patients and can severely impact quality of life. This is a high priority for patients but unlikely to receive industry funding. The PLRH, PKD Charity, 8 patients and international nephrologists held a workshop in May 2017 to explore the topic and consider feasible trial designs.
We proposed an observational study where participants could enter their own data through a secure website, completing standardised questionnaires and testing a new ADPKD-specific pain assessment tool. The aim is for this website to link with existing electronic health records, allowing researchers to track patient report and clinical outcomes. In 2019 we were pleased to have been awarded funding from NIHR Research for Patient Benefit for this work; this study is now led by Dr Ragada El-Damanawi at the University of Sheffield.
Ketogenic Diet Therapy in r(20) Syndrome
Ring Chromosome 20 Syndrome (r(20)) is an extremely rare and under-diagnosed disease, characterised by refractory (hard to treat) epilepsy. Ketogenic diet therapy (KDT) is a viable and accepted treatment for children with refractory epilepsy, but very little is known about its specific use in r(20). Ring 20 Research & Support UK wanted to learn more about KDT prescription, challenges and benefits, with the aim of improving resources for r(20) patients and families.
We completed a literature review to understand the current use of KDT in refractory epilepsies, and conducted online surveys to assess KDT experience within the medical profession and r(20) patients, families and carers. We then hosted a workshop with r(20) families, neurologists, dieticians, and researchers to interpret the findings and plan our next steps. The project was awarded a Starter Fund grant by the University of Cambridge Public Engagement Team.
As r(20) is an ultra-rare disease, Ring 20 Research & Support UK will combine resources and take this project forward in collaboration with EpiCARE (the European Reference Network for rare and complex epilepsies). Contact the charity if you’d like more information, or to be involved with upcoming research.
SUSTAIN
Supplementing sodium to alleviate potassium wasting nephropathy: a randomised trial in Gitelman Syndrome
Gitelman Syndrome (GS) is a rare kidney disorder where magnesium, potassium and salt are wasted into the urine instead of being re-absorbed into the blood stream. Patients take high doses of multiple supplements every day to compensate for the lost electrolytes, but this causes unpleasant gastrointestinal side effects and presents a high medication burden.
Following the success of K+ Monitor, patients from Gitelman Syndrome UK proposed a study to investigate oral salt intake. A high-dose salt tablet may physiologically improve blood potassium and magnesium, reducing required medication and side effects.
Gitelman Syndrome UK, PLRH, Cambridge Clinical Trials Unit and expert nephrologists applied to three separate funding streams with variations of this proposal: Kidney Research UK, JP Moulton, and NIHR Research for Patient Benefit. Unfortunately we have not been successful, and thus are unable to continue work on this project.
DRINK
Determining feasibility of randomisation to high vs. ad libitum water intake in polycystic kidney disease: the DRINK randomised feasibility trial
Autosomal Dominant Polycystic Kidney Disease (ADPKD) is a common inherited condition where unrelenting cyst growth can cause kidney failure. Some research suggests that drinking water beyond the point of thirst can slow cyst growth by suppressing the hormone vasopressin.
Proposed by the UK PKD Charity, DRINK assessed if ADPKD patients could reliably drink enough water to warrant a large-scale trial. 42 participants were divided into ‘high’ and ‘ad libitum’ (aka usual) water intake groups. Participants recorded their own data through a smartphone app for 8 weeks and attended 3 clinical assessments. Our trial team found that the ‘high water’ group was able to maintain dilute urine at a level signifying reduced vasopressin production. Recruitment was successful and the two groups clearly had different levels of water intake, which means a large-scale trial is possible. The next phase is being taken forward by the charity and another research group, and will likely combine water intake with other medication.
Funding for DRINK was provided by the British Renal Society and Kidney Care UK (formerly British Kidney Patient Association) grant programme, PKD Charity, Addenbrooke’s Charitable Trust, and Kidney Research UK. Trial registration NCT02933268 and ISCRTN16794957. Contact PKD Charity if you’d like to be involved in upcoming research.
K+ Monitor
Hand-held potassium monitor for home use in Gitelman Syndrome
Gitelman Syndrome (GS) is a rare kidney disorder where magnesium, potassium and salt are wasted into the urine instead of being re-absorbed into the blood stream. Patients take high doses of multiple supplements every day to compensate for the lost electrolytes, but this causes unpleasant gastrointestinal side effects and presents a high medication burden.
Patient members of Gitelman Syndrome UK proposed the idea of a hand-held, finger-prick device that could be used to monitor their blood potassium levels. The device would be similar to glucometers with disposable chips used regularly by diabetics. An immediate reading of blood potassium would enable patients to dose accordingly, ideally reducing the number of tablets and subsequent side effects.
In collaboration with the Department of Chemistry, University of Cambridge and initially funded by Kidney Research UK and Addenbrooke’s Charitable Trust, the device and sensors have been developed. Led by Prof Fiona Karet, the team delivered a successful proof-of-concept trial with 50 participants. Prof Karet has now established Kalium Health Ltd to continue the clinical development of the sensor.