Trial of ondansetron as a treatment for hallucinations in Parkinson's: an update

What is the TOP HAT trial?

This major trial funded through Parkinson's UK's Virtual Biotech programme set out to test a drug called ondansetron in people with Parkinson's or Lewy body dementia (LBD) who experience visual hallucinations.

Ondansetron is a drug that is already approved and in use in the UK, mainly to help reduce nausea in people undergoing cancer treatment. The drug first showed potential for treating visual hallucinations in Parkinson's in the early 1990s.

A nationwide study to test ondansetron for safety and effectiveness

Chief Investigator, Professor Suzanne Reeves from University College London, explains the aims of the TOP HAT trial:

"Up to 75% of people with Parkinson's may experience hallucinations at some point but current treatment options can cause side effects and increase mortality (risk of death).

"We desperately need better treatments to help people who experience hallucinations as part of their Parkinson's and small studies have suggested that ondansetron could have potential.

"That's why we were keen to put it to the test in a large-scale study. More than 40 hospitals and clinics across the UK joined in the effort to achieve our goal of enrolling several hundred participants.

"We wanted to investigate whether ondansetron is better than a placebo at reducing the frequency and severity of visual hallucinations.

"Secondly, we wanted to understand whether ondansetron would be safe and well-tolerated in people with Parkinson's - this is always a vital question for any potential new treatment."

Why is the study closing early?

As in all clinical trials, an independent team, called the Data Monitoring and Ethics Committee (DMEC), was set up to monitor the trial.

For TOP HAT they carefully monitored a wide range of things. These included known side effects of ondansetron on things such as heart rate and rhythm, constipation and headache. It also included other events such as falls, attendance at A&E, hospital admissions and deaths.

After the first 100 participants had taken part in the study a preliminary analysis was carried out to look at how well the study drug was tolerated and address any safety concerns as promptly as possible.

After looking at this data, the DMEC recommended that recruitment to the TOP HAT trial should stop as there were more safety issues in those who received ondansetron than the placebo.

It is disappointing that the TOP HAT trial is stopping earlier than planned but any sign that a drug may be causing harm means the study must stop.

Next steps for the trial

All current participants have been asked to stop taking their study drugs (ondansetron or placebo) but will continue to be monitored to record any further safety issues as well as to assess their hallucinations.

In the coming months the TOP HAT team will finish collecting all the data from remaining participants in the study. 

They will then be able to conduct the final analysis. This will include looking in more detail at all the safety issues reported throughout the study as well as to see whether ondansetron had a beneficial effect on hallucinations. This will then inform whether ondansetron is still a viable option to be explored further for people with Parkinson's. 

Arthur Roach, Director of the Parkinson's Virtual Biotech at Parkinson's UK, comments:

"We are very grateful to every person who has taken part in this pioneering study. The results will give us vital information about the safety and effectiveness of ondansetron for people with Parkinson's. We will work with the TOP HAT team to share the full findings from this important study as soon as we can.

"If you or a loved one has participated in the study and you have further questions please contact the hospital team where you participated in the trial in the first instance."