The world's largest clinical trial platform for Parkinson's disease has begun recruiting participants across the UK, marking a transformative approach to testing potentially disease-modifying treatments. The Edmond J. Safra Accelerating Clinical Trials for Parkinson's Disease (EJS ACT-PD) platform represents a £26 million investment designed to accelerate the search for effective therapies by testing multiple drugs simultaneously.
Led by Professor Tom Foltynie from University College London and Professor Camille Carroll from Newcastle University, EJS ACT-PD is the first multi-arm, multi-stage (MAMS) clinical trial platform for Parkinson's in the UK. The platform will initially recruit 1,600 people living with Parkinson's disease, providing unprecedented opportunities for patient participation in clinical research.
Revolutionary Trial Design Accelerates Drug Development
Traditional clinical trials test a single drug against a placebo group, a process that researchers compare to "building a football stadium, playing a single game, and then dismantling the stadium, only to restart the process for each trial." The MAMS platform fundamentally changes this approach by testing multiple treatment groups against one shared placebo, allowing several drugs to be evaluated in the time it would typically take to test one.
The platform's adaptive design enables new treatments to be added or swapped in as others conclude or fail to show positive findings during interim evaluations. This flexibility not only speeds up the trial process by enabling simultaneous testing but also provides the infrastructure necessary to support new trials and facilitate continuous transitions between phases of clinical testing.
"It is really exciting to see such a large clinical trial platform that will be testing multiple agents at the same time," said Dr Simon Stott, Director of Research at Cure Parkinson's. "We have the option to take out drugs that aren't working and replace them with alternatives. Rather than the stop-start nature of current trials, this new format will allow for the continuous testing of new therapies that could potentially slow, stop or reverse Parkinson's."
Three Repurposed Drugs Target Different Mechanisms
The initial phase will test two potentially disease-modifying therapies: telmisartan and terazosin. A third treatment arm featuring ursodeoxycholic acid (UDCA) will be added in 2026. All three drugs are repurposed from other medical conditions and were previously evaluated by the International Linked Clinical Trials (iLCT) committee, a group of Parkinson's experts who annually rank and prioritize promising therapies for clinical trial.
Telmisartan, an angiotensin receptor blocker used to treat hypertension, works by blocking the hormone angiotensin from binding to the angiotensin II type 1 receptor (AT1R). Evidence suggests that overactivation of AT1R promotes inflammation and oxidative stress, two drivers of nerve cell loss in Parkinson's disease. By reducing AT1R activity, telmisartan may provide neuroprotective effects.
Terazosin, an alpha 1-adrenergic receptor antagonist typically used for enlarged prostate and hypertension, may help correct mitochondrial dysfunction by increasing activity of phosphoglycerate kinase 1 (PGK1), an enzyme associated with the first step of energy production. Since mitochondrial issues and inadequate cellular energy levels are considered drivers of neuron loss in Parkinson's, terazosin may help address this fundamental problem.
UDCA, a naturally occurring bile acid approved in the 1980s for gallstones and primary biliary cirrhosis, has shown potential to improve mitochondrial function. In 2013, Professor Bandmann and colleagues at Sheffield performed a large-scale screening study of 2,000 compounds using skin cells from people with Parkinson's. The team found UDCA could rescue mitochondrial function and normalize energy levels in cells, leading to its prioritization for clinical trial by the International Linked Clinical Trials committee in 2015.
Addressing Critical Bottlenecks in Drug Development
The platform addresses a significant challenge in Parkinson's drug development: the transition from phase 2 to phase 3 trials. In 2023, there were only three phase 3 trials for potentially disease-modifying therapies. As a late-stage platform, EJS ACT-PD will facilitate the movement of promising treatments from phase 2 to 3 without requiring a complete restart of the trial process.
"Testing multiple treatments is just one way the platform accelerates the clinical trial process," according to the research team. The continuous nature of the platform eliminates the traditional stop-start approach, allowing for ongoing evaluation of new therapies.
Enhanced Accessibility and Patient-Centered Design
The EJS ACT-PD consortium spent five years bringing together researchers, charities including Cure Parkinson's, and people with Parkinson's to design an accessible trial that delivers meaningful results. The platform will operate across over 40 sites in England, Wales, Scotland, and Northern Ireland, with sites in London and Newcastle already open and the remaining sites expected to open over the next six months.
Recognizing the challenges faced by people with Parkinson's, the trial offers virtual study visits as an alternative to in-clinic appointments. Additionally, medications will be delivered directly to participants' homes, reducing travel burden. These accessibility features were directly influenced by people with Parkinson's who participated in the Patient and Public Involvement and Engagement (PPIE) working group.
"Having Parkinson's can be frightening and lonely; it's easy to lose hope," said Katy O'Malley, who lives with Parkinson's and is a member of the EJS ACT-PD PPIE working group. "We need a treatment to slow or stop the progression of this disease, urgently. This trials platform has the potential to knock years off the time this will take, so I really hope it gives people with Parkinson's a good reason to stay positive."
Helen Matthews, CEO of Cure Parkinson's, emphasized the collaborative achievement: "Thanks to this innovative clinical trial programme, more people with Parkinson's than ever before will have the opportunity to participate in disease-modifying research. We're proud to have played a key role in the collaborative effort, bringing partner funders Van Andel Institute, The Gatsby Charitable Foundation, with The John Black Charitable Foundation and our own donors together to realise this project."
The launch of EJS ACT-PD recruitment represents a significant milestone in Parkinson's research, offering new hope for the development of treatments that could slow, stop, or reverse disease progression while providing unprecedented opportunities for patient participation in clinical research.
