EJS ACT-PD: The Edmond J Safra Accelerating Clinical Trials for Parkinson’s trial

Traditionally, clinical trials have involved the testing of a single drug against a single placebo (dummy drug) group. This is a time-consuming, slow, and expensive process, which must be redone each time researchers want to test a new drug. It is comparable to building a football stadium, playing a single game, and then dismantling the stadium, only to restart the process for each trial.

A multi-arm, multi-stage (MAMS) platform is a clinical trial model that involves testing multiple treatment groups against one placebo. This allows several drugs to be tested in the time it would usually take to test one.  This accelerates the progression of therapies through the drug development pipeline. MAMS platforms are also adaptive, allowing new treatments to be added or swapped in as others conclude or do not show positive findings during interim evaluations. This flexibility effectively speeds up the trial process, not only by enabling multiple treatments to be tested simultaneously, but also by providing the infrastructure necessary to support new trials and facilitate continuous transitions between phases of clinical testing.

Learn more about MAMS platforms in this webinar.

In the first instance, EJS ACT-PD will have two treatment arms, testing telmisartan and terazosin. A third arm for ursodeoxycholic acid (UDCA) will be added in 2026.

All three drugs are repurposed from other medical conditions and were previously evaluated by our International Linked Clinical Trials (iLCT) committee – a group of Parkinson’s experts who meet annually to rank and prioritise promising therapies for clinical trial.

Telmisartan

Telmisartan is an angiotensin receptor blocker (ARB) used to treat hypertension (high blood pressure). It works by blocking the hormone angiotensin from binding to its associated receptor, angiotensin II type 1 receptor (AT1R); this prevents it from having an effect.

Receptors are proteins that other proteins bind to in order to change cell activity. You can think of this like a lock and key, where other proteins are the “key” that have a specific “lock” or receptor that they bind to.

Although angiotensin plays a major role in controlling blood pressure, evidence also suggests it may also be associated with several neurological conditions, including Parkinson’s. This is because overactivation of AT1R is associated with promoting inflammation and oxidative stress – two drivers of nerve cell loss in Parkinson’s. Therefore, if telmisartan can reduce AT1R activity, it may have a protective effect.

Terazosin

Terazosin is an alpha 1-adrenergic receptor (α1-AR) antagonist used to treat prostatic hyperplasia (enlarged prostate) and hypertension. It works by blocking specific neurotransmitters (chemical messengers for nerve cells) from binding to their receptor (α1-AR).

Evidence suggests, however, that terazosin may also help correct issues with the mitochondria – the part of the cell that produces energy. It does this by increasing activity of an enzyme associated with the first step of energy production, phosphoglycerate kinase 1 (PGK1). Since issues with the mitochondria and maintaining adequate levels of cellular energy are considered a driver of neuron loss in Parkinson’s, terazosin may help correct this.

UDCA

UDCA is a naturally occurring bile acid which was approved for use in the 1980s to treat gallstones and a rare form of liver disease called primary biliary cirrhosis. Additional research since has shown that UDCA may also have a positive effect on mitochondria – the part of the cell that produces energy. Issues with mitochondria are thought to be a driver of nerve cell (neuron) loss in Parkinson’s; therefore, if UDCA can help restore energy production, it may be able to slow progression.

In 2013, Prof Bandmann and colleagues at Sheffield performed a large-scale screening study to assess 2,000 compounds for their ability to improve energy production. Using skin cells from people with Parkinson’s, the team found UDCA could rescue mitochondrial function and normalise energy levels in cells. This, alongside other similar studies, led to UDCA being prioritised for clinical trial by the International Linked Clinical Trials committee in 2015.

The EJS ACT-PD trial will be taking place at over 40 sites over England, Wales, Scotland and Northern Ireland. You can find a full list of trial sites on the EJS ACT-PD website.

The trial team are working with local sites to train and prepare staff at all local sites. Some sites will be ready quickly, while others will take more time. They hope to have all sites open and ready to recruit participants by mid-2026.

If you decide you would like to take part, you should complete the registration of interest form. You can access the form here: Register your Interest. If you need help completing this form online, your health teams, GP, family or friends can assist with this.

• Treatment Selection and Prioritization for the EJS ACT-PD MAMS Trial Platform – https://doi.org/10.1002/mds.30190
• Improving recruitment and retention of people with Parkinson’s disease to clinical studies: A scoping review – https://doi.org/10.1177/1877718X241291986
• Patient and Public Involvement and Engagement in the Development of a Platform Clinical Trial for Parkinson’s Disease: An Evaluation Protocol – https://doi.org/10.3233/JPD-230444
• Towards a multi-arm multi-stage platform trial of disease modifying approaches in Parkinson’s disease – https://doi.org/10.1093/brain/awad063
• Outcome Measures for Disease-Modifying Trials in Parkinson’s Disease: Consensus Paper by the EJS ACT-PD Multi-Arm Multi-Stage Trial Initiative – https://discovery.ucl.ac.uk/id/eprint/10174972/
• Embedding patient voice in trial design: the EJS ACT-PD experience – https://doi.org/10.1136/jnnp-2022-abn2.153