The world's largest-ever clinical trial of treatments to slow or stop the progression of Parkinson's disease has launched, led by researchers at UCL and Newcastle University.
The £26 million project is accelerating the search for effective treatments with an innovative, flexible trial design testing multiple treatments in parallel. By testing more drugs more efficiently than ever before, the trial could take up to three years off the time needed to test a drug candidate.
The trial team is recruiting up to 1,600 participants in its first phase from more than 40 hospitals across England, Wales, Scotland and Northern Ireland. The trial is now underway, as participants are already being recruited at the London (UCLH) and Newcastle (Clinical Ageing Research Unit) sites, with the other trial sites to get underway between now and next April. People with Parkinson's can register their interest in participating using a simple online form.
Parkinson's disease is one of the world's fastest growing neurological conditions, with 166,000 people affected in the UK today. Parkinson's gets progressively worse and although there are treatments that can help with symptoms, these become less effective over time, so there is an urgent need to find treatments that can slow or stop the disease progression.
The Edmond J Safra Accelerating Clinical Trials in Parkinson's Disease (EJS ACT-PD) trial is sponsored by UCL and funded by a Medical Research Council (MRC) and National Institute for Health and Care Research (NIHR) partnership, Cure Parkinson's, The Michael J. Fox Foundation, Parkinson's UK, The John Black Charitable Foundation, The Gatsby Charitable Foundation and Van Andel Institute.
Co-chief investigator Professor Thomas Foltynie of the UCL Queen Square Institute of Neurology, and consultant neurologist at UCLH's National Hospital for Neurology and Neurosurgery (NHNN), said: "Parkinson's disease is the second most common neurodegenerative disease worldwide, and yet there are no treatments that can slow its relentless progression. We are prioritising drugs that already show promise as potential treatments, based on an extensive review of prior evidence, as we seek to identify a drug that does more than just provide symptom relief for Parkinson's. We hope this trial will serve as a blueprint for future trials in Parkinson's and other neurodegenerative conditions.
"Our trial's wide UK coverage ends the postcode lottery for clinical research, so that underserved populations with Parkinson's can participate in this highly inclusive trial."
Co-chief investigator Professor Camille Carroll (Newcastle University) said: "Our innovative trial design will enable us to accelerate the hunt for an effective treatment in a giant step forward for Parkinson's research, as we will be trialling multiple drugs simultaneously, adapting as we go along based on what we're learning.
"It's a real group effort, and we are particularly grateful to the people with Parkinson's and care partners who are making invaluable contributions to this research. With their input we have designed a trial that we hope will be available and accessible to people with Parkinson's across the UK."
The new EJS ACT-PD trial is using a multi-arm, multi-stage design, enabling several treatments to be tested at the same time, in comparison to a single group of participants taking a placebo, a method which has not been used before for Parkinson's. Initially, the trial will be testing two drugs known to be safe and effective at treating other conditions: a blood pressure medication and a drug used to treat an enlarged prostate.
The first participant to be recruited into the trial at UCLH's National Hospital for Neurology and Neurosurgery, Graham Edwins, commented: "I wanted to be part of EJS ACT-PD because of the pioneering approach to test multiple medications in a single trial. Having Parkinson's, especially young onset, your choices are denial, acceptance or to fight back, which is what I feel I am doing by taking part. Even if I don't directly benefit, if I can help progress a potential treatment or cure for the next person diagnosed in their prime then it's a job well done."
By analysing results on an ongoing basis, ineffective treatments can be identified and dropped from the trial, with more promising drugs progressing. The design's flexibility also allows new treatment arms to be introduced within the same trial infrastructure.
The current standard clinical trials process is hugely time and resource consuming and stop-start in nature, taking up to 10 years for a single potential treatment to complete assessment. Compared to running individual trials for each treatment, the structure of the EJS ACT-PD trial can accelerate the assessment process by close to 25% (or up to three years).
People with Parkinson's, their partners and carers, and community representatives have been involved in every aspect of the trial design. Dr Kevin McFarthing, chair of the trial's patient and public inclusion and engagement working group, commented: "By accelerating clinical research, this trial means that drugs that slow or stop the progression of Parkinson's are coming closer for people like me and for generations to come. I feel very fortunate to be contributing to this excellent initiative that will hopefully make a difference to people with Parkinson's and, of course, to our families."
The sheer scale of the trial provides a unique opportunity to embed research studies within the trial. Sub-studies funded by The Michael J. Fox Foundation are assessing whether wearable technologies could be used to digitally monitor symptoms, and to search for specific and sensitive molecular signatures of Parkinson's in samples from participants.
Professor Sonia Gandhi (UCL Queen Square Institute of Neurology and The Francis Crick Institute), who is co-leading the EJS ACT-PD trial innovation programme, said: "This research will tell us which drugs might be effective, but critically why and how a drug may be working, and who may respond to it - it will change the way we monitor Parkinson's in future trials."
More about Parkinson's disease and the trial:
Parkinson's disease causes difficulty with movement, such as slowness, stiffness and tremor, and other symptoms such as depression, memory problems, bladder and bowel difficulties and sleep disturbance. Parkinson's is degenerative and symptoms become increasingly severe and debilitating as the condition progresses.
The trial will begin by testing two repurposed drugs: telmisartan, a medication for high blood pressure, and terazosin, most commonly used to treat an enlarged prostate. The scientists aim to add a third drug, ursodeoxycholic acid (UDCA), currently used for liver disease, in 2026.
The trial, sponsored and managed by the MRC Clinical Trials Unit at UCL, is now underway, with participants already being recruited at the Leonard Wolfson Experimental Neuroscience Centre, UCL, supported by the NIHR UCLH Biomedical Research Centre, and at the Clinical Ageing Research Unit in Newcastle.
The trial aims to recruit a participant population that is representative of people with Parkinson's in the UK. The trial will recruit people with Parkinson's who were diagnosed aged 30 or older, are taking dopaminergic treatment, and who have not had deep brain stimulation surgery nor infusion treatments.
Eligible participants, once they start taking medication, will be invited to study visits, either in-person or remotely, every six months for up to three years. Trial medication will be delivered to participants' homes to reduce travel burden, particularly for those living in rural areas or with mobility issues.
The team includes researchers, academics, and charities working closely alongside people living with Parkinson's to ensure the trial will suit the needs of those who stand to benefit. People with Parkinson's, their partners and carers, and community representatives have had a major impact on the resulting trial, including using a hybrid delivery approach in which participants can choose to attend study visits either in-person or from home, and assessing results based on a participant's own report of how Parkinson's affects them.
