Azathioprine immunosuppression and disease modification in Parkinson’s disease (AZA-PD): a randomised double-blind placebo-controlled phase II trial


Research summary

Immune activation is strongly implicated in a number of neurodegenerative diseases, including Parkinson’s disease (PD) and related Parkinson-Plus disorders. Our own work has demonstrated not only that there is a genetic link between the immune system and PD risk, but also a more active immune response with raised inflammatory markers in the blood being associated with more rapid progression of the disease. 

This study will test the hypothesis that suppressing the peripheral immune response in PD with azathioprine is an effective disease-modifying strategy. This may ultimately lead to the clinical adoption of a highly cost effective therapy to delay disability and prevent progression to the some of the most feared complications of PD including severe balance problems and dementia, for which we currently have no effective treatments. This therapeutic strategy may also be beneficial for other Parkinson–Plus disorders which share common disease mechanisms.

Main inclusion criteria

  1. Capable of giving signed informed consent
  2. Aged over 50 years
  3. Be a fluent English speaker
  4. Diagnosis of PD according to UKPDS Brain Bank Criteria, though a positive family history of PD will not be used to exclude participants
  5. Disease duration of <3 years
  6. 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):

                  o Haemoglobin ≥ 110 g/L

                  o Platelet count ≥ 130 x 109/L

                  o Neutrophil count ≥ 1.5 x 109/L

                  o Renal Function- creatinine clearance ≥50mL/min.

                  o Hepatic function- ALT and bilirubin ≤2 times the institutional ULN

Main exclusion criteria

  1. Use of prescribed immunomodulatory or anti-inflammatory drugs (see section 9.2 for full details)
  2. Known inflammatory or autoimmune disease, or chronic or latent infection
  3. Active infection requiring the use of parenteral antimicrobial agents within 2 months prior to the first dose of trial treatment
  4. Skin or solid organ malignancy within the 5 years prior to the screening assessment
  5. The inability to take or swallow oral medication
  6. Parkinson’s Disease Dementia according to MDS PD Dementia criteria
  7. Positive test for HIV or hepatitis
  8. TPMT deficiency
  9. Lack of immunity to VZV
  10. Negative EBV IgG
  11. Chronic liver disease
  12. Renal impairment - creatinine clearance <50mL/min
  13. Current or previous haematological malignancy
  14. Concomitant allopurinol
  15. Any concurrent medical or psychiatric condition or disease that is likely to interfere with the trial procedures or results, or that in the opinion of the investigator, would constitute a hazard for participating in this trial
  16. Receipt of live, attenuated vaccine within the 30 days prior to the screening assessment
  17. Women of childbearing potential. Female patients must be surgically sterile or be postmenopausal.
  18. Male patients must be surgically sterile or must agree to use effective contraception during the period of therapy and for 6 months after the last dose of the trial treatment
  19. Known hypersensitivity to azathioprine or its excipients
  20. Received an investigational drug or used an invasive investigational medical device within 4 weeks before the screening assessment or is currently enrolled in an interventional investigational trial

Chief investigator

Dr Caroline H. Williams-Gray

Contact details

Clinical Trial Coordinator: Sonakshi Kadyan

Telephone: 01223 349007 | Email: