The ASPro-PD trial is now underway

PD Frontline is an online genetic testing platform for people with Parkinson’s in the UK. Participants who meet the preliminary criteria for the ASPro-PD study are sent a saliva kit, which is then analysed to determine whether the individual is a carrier of one of two genetic variations associated with Parkinson’s – GBA1 and LRRK2. Due to the link between ambroxol and GCase, half of the ASPro-PD cohort will be people with GBA1 variations, meaning it is necessary for all participants in the trial to undergo genetic screening.

Learn more about PD Frontline by visiting their website: https://pdfrontline.com/en.

Ambroxol has been shown to boost the activity of an enzyme called glucocerebrosidase (GCase), which is known to help clear away waste products in cells. In Parkinson’s, a build-up of a troublesome protein called alpha-synuclein is often seen in brain cells called neurons. It’s thought that ambroxol may help improve the body’s ability to clear away these clumps of alpha-synuclein and prevent damage to brain cells. Previous studies have suggested that ambroxol may improve lysosomal function, which is important for clearing cellular waste in neurons.

Results from a trial of the drug which were published in 2020, funded and supported by Cure Parkinson’s and its strategic partners, showed that ambroxol was safe for people with Parkinson’s to take. It also showed that the drug could reach the brain and boost levels of GCase.

The ASPro-PD trial will test the ambroxol in a larger group of people with Parkinson’s. It will compare it to a dummy drug to see if it can slow the progression of the condition.

Genes are segments of DNA that help direct cell activity. One of their most important roles is in providing the cell with instructions for building proteins. Small changes or variations in our genes can therefore lead to issues with their associated proteins.

There’s some evidence to show that people that have a change in a gene called GBA1, which is associated with Parkinson’s, might benefit from treatment with ambroxol. This is because the GBA1 gene contains the instructions to make an enzyme involved in dealing with cellular waste, called GCase. Variations in the gene mean that the enzyme may not function properly, which can increase the risk of developing Parkinson’s. Ambroxol is thought to help increase GCase activity.

The ASPro-PD study team wants to know if there’s any difference in how ambroxol works for people with and without the GBA1 mutation. They’d like to include a fair balance of people with and without the mutation in the study. To do this, they need to establish whether someone has the mutation before they start in the trial.

The PD Frontline study is an online genetic testing platform which involves taking a saliva sample. This sample is then analysed by the team to look for mutations in genes associated with Parkinson’s, including GBA1. All recruitment to ASPro-PD will come from people who have taken part in the PD Frontline study, regardless of whether they have a GBA1 variation or not.

This depends on the outcome of the trial and regulatory approval processes, which can take several years. The study will be recruiting until 2027, and each participant will be part of the study for 2.5 years.

Parkinson’s UK and Cure Parkinson’s are working with regulators and pharmaceutical companies to try and speed up the approval process. You can read more about this on our websites.

Yes, participants will have to stop taking ambroxol after the trial.

The ASPro-PD trial of ambroxol is a multi-centre study that will take place across approximately 15 NHS research sites in the UK, with UCLH (University College London Hospitals) as a key centre. The specific locations of the sites will be announced on the ASPro-PD website as sites open.

The ASPro-PD research team is reaching out to people who are eligible to take part and who have already pre-registered through the PD Frontline study. This is a study where people are asked to supply a saliva swab, which is then studied to look for changes in certain genes.

People who meet the criteria for ASPro-PD, and have already taken part in PD Frontline, will be invited to visit one of 15 study sites over England, Scotland and Wales. You will be contacted directly by the ASPro-PD team if you fit these criteria. We encourage people to get in touch with the ASPro-PD team if they have any questions.

If you haven’t already registered and taken part in PD Frontline, you may not be able to join the ASPro-PD study. However, you can still register to get genetically tested by PD Frontline and explore other research opportunities through the Parkinson’s UK Take Part Hub or Cure Parkinson’s Get Involved with Research page.

The study team will work with people with Parkinson’s who:

• Have already supplied a saliva sample as part of the PD Frontline study, which looks at whether they have changes in the GBA and LRRK2 genes status,
• Are between 35-75 years old,
• Diagnosed within the last 7 years,
• Have not had Deep Brain Stimulation (DBS) surgery,
• Have not taken exenatide or any other investigational drug for Parkinson’s in the last 12 months.

You won’t be able to take part, even if you meet the above criteria, if you have:

• Participated in a clinical trial of a new or repurposed drug or treatment within 90 days prior to the first dose of trial treatment,
• Used a new or repurposed drug or treatment that is under investigation for treating Parkinson’s within 90 days prior to the first dose of trial treatment,
• Participated in another clinical trial of an investigational new drug being tested for its ability to slow down Parkinson’s progression within 12 months prior to the first dose of trial treatment.

Specific eligibility questions should be directed to the ASPro-PD team at cctu.aspro-pd@ucl.ac.uk.

If you have received and completed a PD Frontline saliva sample, this means that you meet the preliminary criteria for the ASPro-PD trial. Your sample will currently be in the process of being sequenced if you have not yet received your results. Once you receive your results, you will be contacted by the PD Frontline team regarding consent to share your details to participating trial sites.

If you sent your sample over 1 year ago and have not received your results in the predicted timeframe and you are concerned, you can contact the PD Frontline mailbox for an update (pdfrontline@ucl.ac.uk). Please note that they release results as soon as they are available.

The risks of ambroxol are still being studied, and like any medication, there may be side effects. In the pilot study of ambroxol, the reported side effects were generally mild. The ASPro-PD trial will be longer, however, as it is designed to assess both efficacy and safety. The longer treatment period will highlight any possible negative consequences of taking ambroxol.

The ASPro-PD trial will be taking place at 15 sites over England, Scotland and Wales. While the trial has started with the first participant taking part in London, not all of the 15 sites are ready to start seeing participants.

The ASPro-PD team is working with local sites to train and prepare staff at all local sites. Some sites will be more ready, while others will require more time. The study team hopes that all sites will be open and ready by the end of 2025. Recruitment into the trial is planned over the next 2 years.

If you have been made aware that you are eligible from the PD Frontline team but have not yet been introduced to your local ASPro-PD study team, it’s likely that your local site is not yet open.

Unfortunately, no. The ASPro-PD trial is a multi-centre study that will take place across approximately 15 NHS research sites in the UK, with UCLH (University College London Hospitals) as a key centre.

The eligibility criteria require a Parkinson’s diagnosis within the last seven years. Sites have been asked to prioritise those with approaching exclusion criteria for enrolment if they are deemed eligible.

People diagnosed more than seven years ago are not eligible for this trial. You can find more information about other trials on the Parkinson’s UK and Cure Parkinson’s websites.

Yes, the trial will recruit participants both with and without the GBA1 variant.

The ASPro-PD team will be contacting people to take part through the PD Frontline study, so unfortunately you wouldn’t be able to take part unless you have been part of PD Frontline.

If you contact the PD Frontline team, they may be able to direct you to other clinical trials that are relevant to you. You can contact them at pdfrontline@ucl.ac.uk.

You can find many opportunities to take part in research by searching the Parkinson’s UK Take Part Hub or the Cure Parkinson’s Get involved with research page.

No. Currently, saliva test kits are prioritized for participants eligible for the ASPro-PD study. So, if you don’t meet the preliminary eligibility criteria for ASPro-PD, you won’t be sent a kit.

The goal is to expand testing to a wider group of people with Parkinson’s in the future, however due to capacity within the research team it’s necessary to prioritise this way for the moment.

Yes, genetic results are needed for eligibility in certain trials like the ASPro-PD study. But if you are eligible for ASPro-PD, your details will be passed on to the ASPro-PD research team automatically.

If you fulfil the preliminary eligibility criteria for the ASPro-PD trial (aged between 35 – 75 years old and diagnosed within the last 7 years), you will receive a saliva testing kit. This can take up to 5 weeks to arrive. You will be emailed when the kit has been sent. Please check your spam folder if you haven’t heard as these emails can sometimes be misdirected to spam.

The timeline varies, but there have been significant delays due to high demand, staffing shortages, and the complexity of sequencing the GBA1 gene.

The PD Frontline team is currently anticipating sequencing to take up to 1 year from the date we received your sample. They have recently received over 1,000 sequencing results which are currently being worked through and returned to participants. This is done manually and takes some time, but they are working as fast as they can to get the results to participants.

If you have not received your results in the predicted timeframe and you are concerned, you can contact the PD Frontline mailbox for an update (pdfrontline@ucl.ac.uk).

Most samples remain viable, but if needed, participants may be contacted for a new sample (eg: in the instance of a sample repeatedly failing testing.) You’ll hear directly from the PD Frontline team if this is the case.

If you have received and completed a saliva sample, this means that you meet the preliminary criteria for the ASPro-PD trial. Your sample will currently be in the process of being sequenced if you have not yet received your results.

Once you receive your results, you will be contacted by the PD Frontline team regarding consent to share your details to participating trial sites.

The PD Frontline team regularly sends trial updates, newsletters, and any further information regarding the study to people who have registered and taken part in PD Frontline. If you have not received any marketing or trial update emails from PD Frontline in the past year, please check your spam folder as some emails may be diverted there.

If you have not received an email or a saliva kit within 5 weeks of registering, unfortunately you are not within the preliminary criteria for ASPro-PD. The team is working to supply kits to people who don’t meet these criteria in the future.

The PD Frontline team checks the mailbox daily for enquiries and aims to respond to all emails within a week. If you have not received any response to a query, please check the following:

1. You are emailing the correct address. The email address for enquiries is pdfrontline@ucl.ac.uk. Please do not email no_reply@pdfrontline.com, as this does not direct messages to the team.
2. Please check your spam folder. Unfortunately, our emails are sometimes diverted to participants’ spam folders, and so information is not delivered to all participants. Please regularly check your spam folders for any communications.
3. All PD Frontline-related enquiries should be directed to the mailbox mentioned above and not any personal email addresses. This helps the team keep track of enquiries.

If you test positive for a genetic variant, the research team will provide guidance on potential testing for family members. Family members can participate in other studies through PD Frontline, such as RAPSODI, without a diagnosis of Parkinson’s.

Parkinson’s UK and Cure Parkinson’s are committed to keeping the wider community up to date as the ASPro-PD trial progresses. You can watch a recording of an update about the ASPro-PD and PD Frontline trials from the Cure Parkinson’s Spring Research Update Meeting.

The delay in recruitment is mainly due to difficulties in reformulating the study drug. In an earlier clinical study, participants had to take 21 pills of ambroxol per day. We have managed to reduce this to just 3 pills per day for the phase 3 ASPro-PD study. Additionally, because the trial is a collaboration between multiple companies, it has added further logistical challenges.