Parkinson's disease MedDRA version: 20.0 Level: PT Classification code 10061536 Term: Parkinson's disease System Organ Class: 10029205 - Nervous system disorders
Conditions
Interventions
Product Name: Azathioprine
Pharmaceutical Form: Tablet
INN or Proposed INN: Azathioprine
CAS Number: 446-86-6
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 25-
Ph
Sponsors
Cambridge University Hospitals NHS Foundation Trust and University of Cambridge
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: • 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. • Aged 50 years or over • Be a fluent English speaker • Have a diagnosis of PD according to UKPDS Brain Bank Criteria • Have a disease duration of =65 years) yes F.1.3.1 Number of subjects for this age range 40
Exclusion criteria
Exclusion criteria: The presence of any of the following will preclude participant inclusion: • Any use of immunomodulatory drugs such as azathioprine, mycophenolate, methotrexate, ciclosporin, cyclophosphamide within the last 12 months • Any previous use of rituximab or alemtuzumab • Previous treatment with corticosteroids for greater than 2 weeks, or any steroid use in the last 3 months • Regular use of non-steroidal anti-inflammatory drugs including aspirin>75mg, naproxen, ibuprofen, meloxicam on more than 2 days per week. • Known inflammatory or autoimmune disease • Chronic or latent infection • Active infection requiring the use of parenteral antimicrobial agents within 2 months prior to the first dose of study treatment. • Skin malignancy or solid organ malignancy within the last 5 years. • Current or previous haematological malignancy • Positive test for HIV or hepatitis • The inability to take or swallow oral medication • Dementia according to Movement Disorder Society dementia criteria • Thiopurine methyltransferase (TPMT) deficiency <10 pmol/h/mg Hb • Lack of immunity to VZV • Negative EBV IgG • Chronic liver disease • Renal impairment - creatinine clearance <50mL/min • Concomitant use of allopurinol (increases risk of myelotoxicity) • Any concurrent medical or psychiatric condition or disease (e.g. active systemic infection, uncontrolled diabetes, acute diffuse infiltrative pulmonary disease) that is likely to interfere with the study procedures or results, or that in the opinion of the investigator, would constitute a hazard for participating in this study. • Receipt of live, attenuated vaccine within the last 30 days. Note: enrolled patients should not receive live, attenuated vaccine while receiving azathioprine nor within 30 days of last dose of azathioprine • • Women of childbearing potential. Female patients must be surgically sterile or be postmenopausal. o Postmenopausal is defined as spontaneous cessation of regular menses for at least 12 consecutive months or follicle-stimulating hormone (FSH) blood levels in the testing laboratory’s respective postmenopausal range with no alternative pathological or physiological cause. • Male patients must be surgically sterile or must agree to use effective contraception during the period of therapy and for 6 months after completion of trial drug • Known hypersensitivity to azathioprine or its excipients • Received an investigational drug (including investigational vaccines) or used an invasive investigational medical device within 4 weeks before treatment protocol registration or is currently enrolled in an interventional investigational study.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To conduct a double-blind randomised control trial of azathioprine versus placebo to provide ‘proof of concept’ through generating early phase data on the impact of azathioprine on clinical outcome measures of motor and cognitive function in PD.;Secondary Objective: To provide ‘proof of mechanism’ through evaluating the effect of azathioprine on brain inflammation (measured with PK-11195 PET) and abnormalities of immune activation in blood and cerebrospinal fluid in PD. To provide data on the safety and tolerability of azathioprine in this population of patients with early Parkinson's disease. ;Primary end point(s): The primary outcome measure is change in MDS-UPDRS gait/axial score in the OFF state over the 12-month treatment period. 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 The MDS-UPDRS part III examination will be videoed during the trial assessments, which will be used retrospectively to ensure inter-rater reliability. ;Timepoint(s) of evaluation of this end point: The MDS-UPDRS will be assessed at the baseline visit and at the treatment end-point, following 12 months' of treatment with the IMP. At each timepoint, the gait/axial subscore will be recorded. The primary endpoint is the change in this score. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): NA;Timepoint(s) of evaluation of this end point: NA | — |
Countries
United Kingdom
Contacts
Public ContactCarrie Bayliss
Cambridge Clinical Trials Unit
Outcome results
None listed