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Abstract
Introduction The immune system is implicated in the aetiology and progression of Parkinson’s disease (PD). Inflammation and immune activation occur both in the brain and in the periphery, and a proinflammatory cytokine profile is associated with more rapid clinical progression. Furthermore, the risk of developing PD is related to genetic variation in immune-related genes and reduced by the use of immunosuppressant medication. We are therefore conducting a ‘proof of concept’ trial of azathioprine, an immunosuppressant medication, to investigate whether suppressing the peripheral immune system has a disease-modifying effect in PD.
Methods and analysis AZA-PD is a phase II randomised placebo-controlled double-blind trial in early PD. Sixty participants, with clinical markers indicating an elevated risk of disease progression and no inflammatory or immune comorbidity, will be treated (azathioprine:placebo, 1:1) for 12 months, with a further 6-month follow-up. The primary outcome is the change in the Movement Disorder Society-Unified Parkinson’s Disease Rating Scale gait/axial score in the OFF state over the 12-month treatment period. Exploratory outcomes include additional measures of motor and cognitive function, non-motor symptoms and quality of life. In addition, peripheral and central immune markers will be investigated through analysis of blood, cerebrospinal fluid and PK-11195 positron emission tomography imaging.
Ethics and dissemination The study was approved by the London-Westminster research ethics committee (reference 19/LO/1705) and has been accepted by the Medicines and Healthcare products Regulatory Agency (MHRA) for a clinical trials authorisation (reference CTA 12854/0248/001–0001). In addition, approval has been granted from the Administration of Radioactive Substances Advisory Committee. The results of this trial will be disseminated through publication in scientific journals and presentation at national and international conferences, and a lay summary will be available on our website.
Trial registration numbers ISRCTN14616801 and EudraCT- 2018-003089-14.
- Parkinson's disease
- therapeutics
- immunology
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Footnotes
Contributors CW-G is the CI of this trial. JG is subinvestigator of this trial. CW-G and JG: study design and writing the protocol. SK, EC and AC: critical review of the protocol. SB: statistical analysis plan.
Funding This trial is funded by Cambridge Centre for Parkinson-Plus (grant no: RG95450) and the Cure Parkinson’s Trust (grant ref CW011) and supported by the NIHR Cambridge Biomedical Research Centre (grant ref no 146281). CW-G is supported by a Research Councils UK/UK Research and Innovation (RCUK/UKRI) Research Innovation Fellowship awarded by the Medical Research Council (MR/R007446/1). This study is jointly sponsored by the University of Cambridge and Cambridge University Hospitals NHS foundation Trust.
Disclaimer The funders have no role in study design; collection, management, analysis, and interpretation of data; writing of the report; or the decision to submit the report for publication.
Competing interests None declared.
Patient and public involvement Patients and/or the public were involved in the design, or conduct, or reporting, or dissemination plans of this research. Refer to the Methods section for further details.
Patient consent for publication Not required.
Provenance and peer review Not commissioned; externally peer reviewed.