AZA-PD
Research type
Research Study
Full title
Azathioprine Immunosuppression and Disease Modification in Parkinson’s Disease (AZA-PD): a randomised double-blind placebo-controlled phase II trial
IRAS ID
243918
Contact name
Caroline Williams-Gray
Contact email
Sponsor organisation
Cambridge University Hospitals NHS Foundation Trust and University of Cambridge
Eudract number
2018-003089-14
Duration of Study in the UK
2 years, 8 months, 1 days
Research summary
Lay summary of study results: AZA-PD was a clinical trial run from a research clinic setting in Cambridge UK, and set out to investigate whether suppressing the peripheral immune system could slow down the progression of Parkinson’s disease. Trial participants were treated with either an immunosuppressant, azathioprine, or placebo for one year. Both the trial participants and the clinical team were unaware of the drug that they were taking (double-blinded trial design).
We did not see a beneficial effect from treatment with azathioprine on our prespecified “primary outcome”, which was a score assessing posture, balance and walking. However, in additional “exploratory” analysis, participants who took azathioprine scored significantly better over the course of the trial on a questionnaire which assessed symptoms relating to problems with movement. When we separate out female participants and analyse their results separately, we see evidence of a more widespread positive effect, with improvement on questionnaires assessing non-motor symptoms and quality of life as well as motor symptoms. This is not enough evidence to suggest treatment with azathioprine in Parkinson’s disease, or a similar immunosuppressive drug, but it is promising finding.
As part of the trial, we also collected blood samples, spinal fluid samples and performed PET brain scans to measure inflammation. Our results show that we impacted on populations of immune cells in the blood and spinal fluid which have been associated with Parkinson’s disease. The analysis of the PET scans suggests that we reduced the spread of brain inflammation with azathioprine. Together, these findings provide evidence that we have achieved our aim of reducing immune activation and inflammation in PD.
This trial has contributed to our understanding of the role of the immune system in Parkinson’s disease, and our next steps are to understand why only some people seemed to respond to treatment. This will help us to design future studies trying to slow down Parkinson’s disease by targeting the immune system.Parkinson's disease (PD) is the most common movement disorder in the UK, affecting approximately 2% of people over 65. It is characterised by its effect on movement; with slowness, stiffness and problems with walking and balance. However, it can also cause problems with bladder and bowel function, sleep, swallowing, speech, mood and memory. It is a progressive disorder; 10 years following diagnosis approximately two thirds of patients have significant walking problems and half have dementia.
There are treatments to help alleviate some of the symptoms, but no therapies to slow the underlying disease process. There is growing evidence suggesting that activation of the immune system plays a significant role in PD. This is a critical system for protecting the body from infections, but can become inappropriately activated in certain diseases, causing tissues to become inflamed and damaged. We are proposing a trial of a drug in PD which acts to suppress the immune system, in the hope that it will slow disease progression. The drug is called azathioprine and its currently used commonly in autoimmune conditions.
We propose trialing azathioprine in a group of recently diagnosed patients (within the last 3 years). We will recruit 60 patients; half will receive azathioprine and half placebo. It will be double-blinded, so that neither the participants nor the researchers know who is taking the active drug. They will take this medication for a year. We will assess the severity of symptoms of PD at the beginning and end and compare the treatment group with the placebo group to see if azathioprine has influenced the progression of the disease. We will also look at markers of immune activation, using brain imaging, and tests on blood and cerebrospinal fluid, to assess the effect of azathioprine on the immune changes previously observed in PD.REC name
London - Westminster Research Ethics Committee
REC reference
19/LO/1705
Date of REC Opinion
6 Nov 2019
REC opinion
Favourable Opinion