Plain English Summary
Background and study aims
Parkinson’s disease (PD) is a long-term medical condition which is caused by the gradual loss of nerve cells (neurons) in a part of the brain called the substantia nigra. These neurons are normally responsible for producing dopamine, a chemical messenger (neurotransmitter) which carries signals around the brain that help to coordinate movement. In people suffering from PD, these neurons gradually die over time, causing the level of dopamine in the brain to gradually fall. As the levels of dopamine become lower, the brain is unable to coordinate movement as effectively, causing abnormal movements such as stiffness, tremor (uncontrollable shaking) and slowness of movement (bradykinesia). Currently, PD affects more than 127,000 people in the UK alone, with a further 10,000 diagnosed each year. Unfortunately, there is no cure for PD and so current therapies are only able to help relieve the symptoms, such as by artificially replacing dopamine or preventing the body from breaking it down. These treatments ultimately fail however, as they are unable to prevent the overall loss of neurons in the brain. Neuroprotection is an area of research which aims to protect nerves from damage. Studies have shown that statins (a group of medications which lower cholesterol) are potentially neuroprotective. The way this works is still only partly understood however, and so more research is needed to find out if statins have the potential of being neuroprotective. The aim of this study is to find out whether simvastatin has potential as a neuroprotective therapy in PD.
Who can participate?
Adults aged between 40 and 90 years old who have been diagnosed with idiopathic PD (i.e. the cause is unknown), with no current or previous use of statins.
What does the study involve?
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 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 these 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.
What are the possible benefits and risks of participating?
Participants may or may not benefit directly from taking part in the study, but by taking part they will be contributing to a study which could potentially bring future benefit to large numbers of people with PD. There are no significant risks of taking part, however participants may experience side effects from the medication (such as muscle aches and pains) and could experience pain or bruising from blood testing.
Where is the study run from?
24 NHS hospitals in England (UK)
When is the study starting and how long is it expected to run for?
January 2015 to September 2020
Who is funding the study?
1. Cure Parkinson's Trust (UK)
2. The JP Moulton Charitable Foundation (UK)
Who is the main contact?
Mr Doug Webb
Trial website
Additional identifiers
EudraCT number
2015-000148-40
ClinicalTrials.gov number
NCT02787590
Protocol/serial number
19666
Study information
Scientific title
Simvastatin as a neuroprotective treatment for Parkinson's disease: a double-blind, randomised, placebo-controlled futility study in patients of moderate severity
Acronym
PD STAT
Study hypothesis
The aim of this study is to establish whether the cholesterol-lowering drug, simvastatin, has potential as a neuroprotective therapy in Parkinson's disease.
Ethics approval
Newcastle and North Tyneside 2 Research Ethics Committee, 12/10/2015, ref: 15/NE/0324
Study design
Double-blind placebo-controlled multi-centre randomised futility study
Primary study design
Interventional
Secondary study design
Randomised controlled trial
Trial setting
Hospitals
Trial type
Treatment
Patient information sheet
Not available in web format, please use the contact details to request a participant information sheet
Condition
Topic: Dementias and neurodegeneration; Subtopic: Parkinson’s Disease; Disease: Parkinson's disease
Intervention
Participants in this study will be randomly allocated to one of two treatment groups in a 1:1 ratio:
Intervention group: Participants will receive oral simvastatin capsules to take daily for 24 months.
Control group: Participants will receive oral matched-placebo capsules to take daily for 24 months.
Trial treatment will be provided to the participants at the baseline, 1 month, 6 month, 12 month and 18 month clinic visits; the maximum supply provided will be a 6 month supply. Bottles containing 100 capsules of either 40mg simvastatin or matched placebo will be issued to the participants.
Over a 26 month period, participants in both treatment groups will attend scheduled study clinic visits, complete a number of validated assessments and receive telephone contacts.
Intervention type
Drug
Phase
Not Applicable
Drug names
Simvastatin
Primary outcome measure
Patient motor skills are determined using the Movement Disorder Society - Unified Parkinson's Disease Rating Scale (MDS-UPDRS Part III) in the OFF state at 12 and 24 months.
Secondary outcome measures
1. The overall impact of PD on the participant is assessed using the MDS-UPDRS total score in the practically defined ON state at 12 and 24 months
2. The impact of PD on activities of daily living is assessed using the MDS-UPDRS part II subscale score in the practically defined ON state at 12 and 24 months
3. Motor skills are assessed using timed motor tests (finger tapping and timed walk test (10MWT)) in the OFF state at 12 and 24 months
4. Depression is assessed using the Montgomery and Asberg Depression Rating Scale (MADRS) at 12 and 24 months
5. Cognition is assessed using the Addenbrooke’s Cognitive Assessment-III (ACE-III) at 12 and 24 months
6. The presence of the non-motor features of PD is captured using the Non-Motor Symptom assessment scale (NMSS) at 12 and 24 months
7. A PD-specific health status is assessed using the Parkinson’s disease Questionnaire (PDQ-39) at 12 and 24 months
8. Changes in PD medication are measured by capturing a levodopa-equivalent dose (LED) at 12 and 24 months
9. Cholesterol levels are captured using total, HDL, LDL, and total/HDL ratio results at 12 and 24 months
10. The presence of PD-specific pain is captured using the King’s PD pain scale (KPPS) at 12 and 24 months
11. A current overall health status is captured using the EuroQoL 5D-5L (EQ-5D-5L) health status questionnaire at 12 and 24 months
12. The safety and tolerability of trial medication is assessed by adverse events (AEs) review at 12 and 24 months
13. The incidence of diabetes mellitus is assessed at 24 months using a glycated haemoglobin (HbA1c) level of 6.5% (48mmol/mol) as diagnostic of diabetes mellitus (WHO 2011)
Overall trial start date
01/01/2015
Overall trial end date
30/09/2020
Reason abandoned (if study stopped)
Eligibility
Participant inclusion criteria
1. Diagnosis of idiopathic PD
2. Modified Hoehn and Yahr stage ≤ 3.0 in the ON medication state
3. Age 40-90 years
4. On dopaminergic treatment with wearing-off phenomenon
5. Able to comply with study protocol and willing to attend necessary study visits
Participant type
Patient
Age group
Adult
Gender
Both
Target number of participants
Planned Sample Size: 198; UK Sample Size: 198
Participant exclusion criteria
1. Diagnosis or suspicion of other cause for parkinsonism
2. 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
3. Concurrent dementia defined by MoCA score <21
4. Concurrent severe depression defined by MADRS score >31
5. Prior intracerebral surgical intervention for PD including deep brain stimulation, lesional surgery, growth factor administration, gene therapy or cell transplantation
6. Already actively participating in a research study that might conflict with this trial
7. Prior or current use of statins as a lipid lowering therapy
8. Intolerance to statins
9. Untreated hypothyroidism
10. 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)
11. eGFR <30 mL/min
12. History of alcoholism or liver impairment
13. Creatine kinase (CK) >1.1 x upper limit of normal (ULN)
14. Aspartate transaminase (AST) or alanine transaminase (ALT) >1.1 x ULN
15. Females who are pregnant or breast feeding or of childbearing potential and unwilling to use appropriate contraception methods whilst on trial treatment
16. Currently taking any medication contraindicated with simvastatin use
17. Any requirement for statin use
18. Regular participation in endurance or high impact sports
19. Unable to abstain from consumption of grapefruit based products
Recruitment start date
01/12/2015
Recruitment end date
31/03/2018
Locations
Countries of recruitment
United Kingdom
Trial participating centre
Royal Cornwall Hospital
2 Penventinnie Lane
Treliske
Cornwall
TR1 3LQ
United Kingdom
Trial participating centre
Derriford Hospital
Derriford Road
Plymouth
PL6 8DH
United Kingdom
Trial participating centre
Musgrove Park Hospital
Parkfield Drive
Taunton
TA1 5DA
United Kingdom
Trial participating centre
Yeovil District Hospital
Higher Kingston
Yeovil
BA21 4AT
United Kingdom
Trial participating centre
Christchurch Hospital
Fairmile Road
Christchurch
BH23 2JX
United Kingdom
Trial participating centre
Royal United Hospital Bath
Combe Park
Bath
BA1 3NG
United Kingdom
Trial participating centre
St Peter’s Hospital
Guildford Road
Chertsey
KT16 0PZ
United Kingdom
Trial participating centre
Charing Cross Hospital
Fulham Palace Road
London
W6 8RF
United Kingdom
Trial participating centre
Royal Free Hospital
Pond Street
London
NW3 2QG
United Kingdom
Trial participating centre
Queen’s Hospital
Rom Valley Way
Romford
RM7 0AG
United Kingdom
Trial participating centre
John Radcliffe Hospital
Headley Way
Oxford
OX3 9DU
United Kingdom
Trial participating centre
Luton and Dunstable University Hospital
The L&D Hospital NHS Foundation Trust
Lewsey Road
Luton
LU4 0DZ
United Kingdom
Trial participating centre
Addenbrookes Hospital
Hills Road
Cambridge
CB2 0QQ
United Kingdom
Trial participating centre
Salford Royal Hospital
Stott Lane
Salford
M6 8HD
United Kingdom
Trial participating centre
Fairfield General Hospital
Rochdale Old Road
Bury
BL9 7TD
United Kingdom
Trial participating centre
Royal Preston Hospital
Sharoe Green Lane North
Preston
PR2 9HT
United Kingdom
Trial participating centre
Leeds General Infirmary
Great George Street
Leeds
LS1 3EX
United Kingdom
Trial participating centre
Clinical Ageing Research Unit
Campus for Ageing and Vitality
Newcastle upon Tyne
NE4 5PL
United Kingdom
Trial participating centre
Royal Devon and Exeter Hospital
Barrack Road
Exeter
EX2 5DW
United Kingdom
Trial participating centre
King's College Hospital
Denmark Hill
Brixton
London
SE5 9RS
United Kingdom
Trial participating centre
Royal Hallamshire Hospital
Glossop Road
Sheffield
S10 2JF
United Kingdom
Trial participating centre
Norfolk and Norwich University Hospital
Colney Lane
Norwich
NR4 7UY
United Kingdom
Trial participating centre
Rotherham General Hospital
Moorgate Road
Rotherham
S60 2UD
United Kingdom
Trial participating centre
Royal Stoke University Hospital
Newcastle Road
Stoke-on-Trent
ST4 6QG
United Kingdom
Funders
Funder type
Charity
Funder name
Cure Parkinson's Trust
Alternative name(s)
Funding Body Type
Funding Body Subtype
Location
Funder name
The JP Moulton Charitable Foundation
Alternative name(s)
Funding Body Type
Funding Body Subtype
Location
Results and Publications
Publication and dissemination plan
The study team will prepare a plain English summary of the study results which will be sent to the study participants as soon as possible after the end of the trial. Results of the study may also be presented at meetings of PD support groups or to other relevant lay audiences. The study results will be submitted for publication in international, high impact, peer reviewed journals relating to neurology and PD. The study findings will be presented at regional, national and international meetings as appropriate.
IPD sharing statement
The data sharing plans for the current study are unknown and will be made available at a later date.
Intention to publish date
01/10/2020
Participant level data
To be made available at a later date
Basic results (scientific)
Publication list
2019 protocol in https://pubmed.ncbi.nlm.nih.gov/31594876/ (added 23/07/2020)