Simvastatin as a Neuroprotective Treatment for Moderate Parkinson's Disease (PD STAT)

University Hospital Plymouth NHS Trust

Status and phase: Completed; Phase 2

Conditions: Parkinson Disease

Treatments: Drug: Simvastatin; Drug: Matched Placebo (for Simvastatin)

Study type: Interventional

Funder types: Other

Identifiers

NCT02787590

PDSTAT2015

16108482 (Registry Identifier)

2015-000148-40 (EudraCT Number)

Details and patient eligibility

About

Participants are randomly allocated to one of two treatment groups. In one group, participants are given capsules of simvastatin to take orally (by mouth) for 24 months. In the other group, participants are given placebo (dummy) capsules to take orally for 24 months. At the start of the study, when they receive their medication, participants complete a number of questionnaires and motor (movement) tests (a walking test and a finger tapping test). Participants in both groups also attend a further 6 clinic visits after 1, 6, 12, 18 and 24 and 26 months, where they are asked about their health and any medication they are taking, as well as repeating the questionnaires and motor tests. For 4 of the clinic visits, the participants will be asked to attend in the 'OFF medication' state (having omitted their usual PD medication) so that the researchers can get a true picture of their disease without it being masked by their normal medication.

Enrollment: 235 patients

Sex: All

Ages: 40 to 90 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Diagnosis of idiopathic PD
• Modified Hoehn and Yahr stage ≤ 3.0 in the ON medication state
• Age 40-90 years
• On dopaminergic treatment with wearing-off phenomenon
• Able to comply with study protocol and willing to attend necessary study visits

Exclusion criteria

• Diagnosis or suspicion of other cause for parkinsonism
• Known abnormality on CT or MRI brain imaging considered to be causing symptoms or signs of neurological dysfunction, or considered likely to compromise compliance with study protocol
• Concurrent dementia defined by MoCA score <21
• Concurrent severe depression defined by MADRS score >31
• Prior intracerebral surgical intervention for PD including deep brain stimulation, lesional surgery, growth factor administration, gene therapy or cell transplantation
• Already actively participating in a research study that might conflict with this trial
• Prior or current use of statins as a lipid lowering therapy
• Intolerance to statins
• Untreated hypothyroidism
• End stage renal disease (creatinine clearance <30 mL/min) or history of severe cardiac disease (angina, myocardial infarction or cardiac surgery in preceding two years)
• eGFR <30 mL/min
• History of alcoholism or liver impairment
• Creatine kinase (CK) >1.1 x upper limit of normal (ULN)
• Aspartate transaminase (AST) or alanine transaminase (ALT) >1.1 x ULN
• Females who are pregnant or breast feeding or of child-bearing potential and unwilling to use appropriate contraception methods whilst on trial treatment
• Currently taking any medication contraindicated with simvastatin use (Appendix 2)
• Any requirement for statin use
• Regular participation in endurance or high-impact sports
• Unable to abstain from consumption of grapefruit-based products

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

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235 participants in 2 patient groups, including a placebo group

Simvastatin

Active Comparator group

Description:

A one month low dose phase of 40mg oral simvastatin daily will be followed by a 23 month high dose phase of 80mg oral simvastatin daily and a final two month phase off trial medication

Treatment:

Drug: Simvastatin

Matched Placebo

Placebo Comparator group

Description:

A one month low dose phase of 40mg matched placebo daily will be followed by a 23 month high dose phase of 80mg matched placebo daily and a final two month phase off trial medication

Treatment:

Drug: Matched Placebo (for Simvastatin)