PRION-1

What was this study about?

Human prion disease affects the central nervous system and then the brain. It causes dementia and eventually death. Currently there is no cure. Human prion diseases are traditionally classified between Creutzfeldt-Jakob disease (CJD), Gerstmann-Sträussler-Scheinker (GSS) disease and kuru. A new human prion disease called variant CJD (vCJD) appeared in the UK in 1995 and was shown to be associated with the same prion disease that causes bovine spongiform encephalopathy (BSE) in cattle. This led to concerns that many people could be affected, so there was a pressing need for research to find a cure.

PRION-1 was the first clinical trial in human prion disease in the UK. A drug called quinacrine had been previously used to treat other diseases such as malaria; however, it causes serious side effects and is no longer prescribed in the UK. It stopped prions copying themselves in test tubes, and seemed to produce benefits when given to one patient in America. When this trial was launched, quinacrine was seen by researchers, patients and doctors as the only drug worth testing in human prion disease.

The aim of the PRION -1 trial was to test whether quinacrine was safe and whether it helped to treat human prion disease. In the trial, one group of patients were to be given quinacrine immediately. The other group were to be given quinacrine after 24 weeks. However, we knew that many patients would not want to take part in a randomised trial, because they want to choose whether or not to take quinacrine for themselves. So as well as inviting people to be randomised into one group or the other, we also followed the experiences of patients who chose whether or not to take quinacrine. This trial was a collaboration between the NHS National Prion Clinic, the MRC Prion Unit and the MRC CTU.

Results

This study found that quinacrine did not significantly affect how prion disease developed. It did not help people to live for longer. Only two patients or the families and carers of patients (if patients were not well enough to give consent themselves) agreed to randomisation, even though the design of the trial meant that all participants would receive quinacrine either immediately or after some time. Affected patients or their carers overwhelmingly preferred to decide for themselves whether to take quinacrine or not, rather than agree to randomisation. This meant that PRION-1 was essentially an observational study not a randomised trial. Most importantly, very few carers and patients chose quinacrine either if they were already very sick, or alternatively had very few symptoms. About half the patients and carers of patients who were mildly or moderately affected chose to take quinacrine, and half chose not to take it.

What difference did this study make?

PRION-1 showed that it is possible to recruit patients to a study about human prion disease, and that patients and their families were willing to stay involved once they agreed to take part.  However, PRION-1 highlighted the difficulty of randomised controlled trials in human prion disease.

Because no potential treatment is likely to reverse the effects of human prion disease, researchers recommended that it might be better for any future trials to recruit people with a mild or moderate form of this disease.  These were also the people who seemed to be most unsure about whether or not they individually felt quinacrine would make a difference to them (see above) – that is, the group of people in whom offering randomisation makes most sense.

Type of study

Observational study

Contact details

enquiries@ctu.mrc.ac.uk

Who funded the study?

This study was funded by Department of Health.