A trial investigating whether suppressing the immune system with azathioprine slows the progression of Parkinson’s disease

INTERVENTION: This study is designed to investigate whether azathioprine can slow the progressive nature of early PD. In order to do this, the researchers propose setting up a clinical trial, where half the participants will take azathioprine and half placebo. It will be double‐blinded, so neither the researchers or participants are aware who is taking the active agent. The researchers will then compare the extent to which both groups have progressed on measures which assess the symptoms of PD. They will also investigate markers of activation of the immune system, using blood, cerebrospinal fluid and imaging, to analyse the effect of the treatment. Potential participants will be identified from the database of attendees of the PD research clinic at the John van Geest Centre for Brain Repair, based on the inclusion and exclusion criteria of the study and using their previous assessments on the database. These patients have previously indicated (provided consent) that they are interested in being contacted about further involvement in research. The researchers aim to randomise 60 patients in total, aged 50‐80 years of age and within 2 years of their diagnosis. They are looking to recruit a cohort of patients who have a poor prognosis; greater than 50% chance dementia, postural instability or death within 5 years, based on a validated predictive calculator. The potential participants will be sent the participant information sheet, and if interested, be invited to attend a screening visit. At this visit, they will first have the opportunity to raise any questions, before being asked to sign the consent form. They will then have their medical history and medication reviewed, before having some blood tests. These assessments are to ensure CONDITION: Parkinson's disease ; Nervous System Diseases ; Parkinson disease PRIMARY OUTCOME: ; Axial and gait symptoms measured using MDS‐UPDRS gait/axial score in the OFF state at 12 months. This score is a sum of the points from the following sections of MDS‐UPDRS part III (motor examination):; 3.1. Speech; 3.2. Facial expression; 3.9. Rising from a chair; 3.10. Gait; 3.12. Postural stability; 3.13. Posture; 3.14. Body bradykinesia; SECONDARY OUTCOME: ; Exploratory outcomes:; 1. Axial and gait symptoms measured using MDS‐UPDRS gait/axial score in OFF state at 18 months (6 months post treatment cessation); 2. Parkinson’s disease severity measured using MDS‐UPDRS parts I, II and III in OFF state at 12 and 18 months; 3. Bradykinesia and tremor measured using electromagnetic sensor (EMS) measurements whilst performing MDS‐UPDRS tremor and bradykinesia assessments at 12 and 18 months; 4. Proportion of patients developing postural instability measured using Hoehn and Yahr stage 3 or greater at 12 and 18 months; 5. Global cognition measured using Addenbrooke's Cognitive Examination III (ACE‐III) at 12 and 18 months; 6. Patient‐reported quality of life measured using Parkinson's disease questionnaire‐39 (PDQ‐39) at 12 and 18 months; 7. Non‐motor symptoms measured using non‐motor symptom scale (NMSS) at 12 and 18 months; 8. Parkinson’s disease treatment measured using the dose of symptomatic dopaminergic therapy (Levodopa‐Equivalent Daily Dose [LEDD]) at 12 and 18 months; 9. Safety and tolerability of azathioprine assessed by the number of adverse events (AEs) recorded during the 12‐month treatment period; 10. Total lymphocyte count measured using a blood test (full blood count) at 6, 12 and 18 months; 11. Serum IgG levels measured using a blood test (immunoglobulins) at 6, 12 and 18 months; 12. Levels of serum immune markers measured using cytokine immunoassays and immunophenotyping at 6, 12 and 18 months and CSF immune markers at 12 months; 13. Microglial activation measured using [11C]‐PK11195 PET non‐dissociable binding potential (BPND) in subcortical and cortical regions of interest at 12 months; INCLUSION CRITERIA: 1. Be capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol 2. Aged 50 years or over 3. Be a fluent English speaker 4. Have a diagnosis of PD according to UKPDS Brain Bank Criteria 5. Have a disease duration of < 3 years 6. Have a probability of poor outcome (postural instability/dementia/death) at 5 years from diagnosis > = 50% 7. Have adequate organ and marrow function, as defined below (measured within 42 days of first dose of trial medication): 7.1. Haemoglobin > = 110 g/L 7.2. Platelet count > = 130 x 109/L 7.3. Neutrophil count > = 1.5 x 109/L 7.4. Renal function‐ creatinine clearance > = 50mL/min 7.5. Hepatic function