Clinical trial NCT02787590: Simvastatin as a Neuroprotective Treatment for Moderate Parkinson's Disease
Official title: Simvastatin as a Neuroprotective Treatment for Parkinson's Disease: a Double-blind, Randomised, Placebo Controlled Futility Study in Patients of Moderate Severity.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Parkinson Disease
Keywords: Neurology
Lead sponsor: University Hospital Plymouth NHS Trust
Sponsor class: OTHER
Collaborators: name: University of Plymouth
First posted: 2016-06-01
Enrollment: 235
Sex: ALL
Minimum age (years): 40
Maximum age (years): 90
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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

Primary outcomes:
measure: Change in MDS-UPDRS part III (OFF) score
timeFrame: Baseline and 24 Months
Secondary outcomes:
measure: MDS-UPDRS total score in the practically defined ON state
timeFrame: at 12 and 24 months
measure: MDS-UPDRS part II subscale score in the practically defined ON state
timeFrame: at 12 and 24 months
measure: Timed motor tests - finger tapping and timed walk test (10MWT) in the OFF state, electromagnetic sensor (EMS) assessment in the OFF and ON state
timeFrame: at 12 and 24 months
measure: Montgomery and Asberg Depression Rating Scale (MADRS)
timeFrame: at 12 and 24 months
measure: The Addenbrooke's Cognitive Assessment-III (ACE-III)
timeFrame: at 12 and 24 months
measure: Non-Motor Symptom assessment scale (NMSS)
timeFrame: at 12 and 24 months
measure: Parkinson's disease Questionnaire (PDQ-39)
timeFrame: at 12 and 24 months
measure: Changes in PD medication as measured by levodopa-equivalent dose (LED)
timeFrame: at 12 and 24 months
measure: Cholesterol levels (total, HDL, total/HDL ratio)
timeFrame: at 12 and 24 months
measure: King's PD pain scale (KPPS)
timeFrame: at 12 and 24 months
measure: EuroQoL 5D-5L health status questionnaire (EQ-5D-5L)
timeFrame: at 12 and 24 months
measure: Safety and tolerability of trial medication by adverse events (AEs) review.
timeFrame: at 12 and 24 months
measure: Incidence of diabetes mellitus, using a glycated haemoglobin (HbA1c) level of 6.5% (48mmol/mol) as diagnostic of diabetes mellitus.
timeFrame: at 24 months
Other outcomes:
Locations:
city: Bath
country: United Kingdom
facility: Royal United Hospital
city: Bournemouth
country: United Kingdom
facility: Royal Bournemouth Hospital
city: Bury
country: United Kingdom
facility: Fairfield General Hospital
city: Cambridge
country: United Kingdom
facility: Addenbrooke's Hospital
city: Chertsey
country: United Kingdom
facility: St Peter's Hospital
city: Exeter
country: United Kingdom
facility: Royal Devon and Exeter Hospital
city: Leeds
country: United Kingdom
facility: Leeds General Infirmary
city: London
country: United Kingdom
facility: Charing Cross Hospital
city: London
country: United Kingdom
facility: King's College Hospital
city: London
country: United Kingdom
facility: Royal Free Hospital
city: Luton
country: United Kingdom
facility: Luton and Dunstable Hospital
city: Newcastle
country: United Kingdom
facility: Clinical Ageing Research Unit
city: Norwich
country: United Kingdom
facility: Norfolk and Norwich University Hospital
city: Oxford
country: United Kingdom
facility: John Radcliffe Hospital
city: Plymouth
country: United Kingdom
facility: Derriford Hospital
city: Preston
country: United Kingdom
facility: Royal Preston Hospital
city: Romford
country: United Kingdom
facility: Queen's Hospital
city: Rotherham
country: United Kingdom
facility: Rotherham General Hospital
city: Salford
country: United Kingdom
facility: Salford Royal Hospital
city: Sheffield
country: United Kingdom
facility: Royal Hallamshire Hospital
city: Stoke-on-Trent
country: United Kingdom
facility: Royal Stoke University Hospital
city: Taunton
country: United Kingdom
facility: Musgrove Park Hospital
city: Truro
country: United Kingdom
facility: Royal Cornwall Hospital
city: Yeovil
country: United Kingdom
facility: Yeovil District Hospital
Study officials:
affiliation: Clinical Lecturer (University of Plymouth) and Honorary Consultant Neurologist, Plymouth Hospitals NHS Trust.
name: Camille B Carroll, BM BCh, PhD
role: STUDY_DIRECTOR
References:
citation: Carroll CB, Webb D, Stevens KN, Vickery J, Eyre V, Ball S, Wyse R, Webber M, Foggo A, Zajicek J, Whone A, Creanor S. Simvastatin as a neuroprotective treatment for Parkinson's disease (PD STAT): protocol for a double-blind, randomised, placebo-controlled futility study. BMJ Open. 2019 Oct 7;9(10):e029740. doi: 10.1136/bmjopen-2019-029740.