Condition category
Nervous System Diseases
Date applied
19/11/2015
Date assigned
19/11/2015
Last edited
24/11/2015
Prospective/Retrospective
Prospectively registered
Overall trial status
Ongoing
Recruitment status
No longer recruiting

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?
At least 20 NHS hospitals in England (UK)

When is the study starting and how long is it expected to run for?
January 2015 to December 2018

Who is funding the study?
1. Cure Parkinson's Trust (UK)
2. The JP Moulton Charitable Foundation (UK)

Who is the main contact?
Miss Victoria Eyre

Trial website

https://penctu.psmd.plymouth.ac.uk/pdstat/

Contact information

Type

Public

Primary contact

Miss Victoria Eyre

ORCID ID

Contact details

Peninsula Clinical Trials Unit
N16
I T T C Building
1 Tamar Science Park
Davy Road
Plymouth
PL6 8BX
United Kingdom

Additional identifiers

EudraCT number

2015-000148-40

ClinicalTrials.gov number

Protocol/serial number

19666

Study information

Scientific title

Simvastatin as a neuroprotective treatment for Parkinson's disease: a double­blind, 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 below 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 gorup: 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 measures

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

31/12/2018

Reason abandoned

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

01/12/2016

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

North Devon District Hospital
Raleigh Park
Barnstaple
EX31 4JB
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

Frenchay Hospital
Frenchay Park Road
Bristol
BS16 1LE
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

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

Sponsor information

Organisation

Plymouth Hospitals NHS Trust

Sponsor details

Research Office
Level 2
MSCP
Bircham Park Offices
Morlaix Drive
Plymouth
PL6 8BQ
United Kingdom

Sponsor type

Hospital/treatment centre

Website

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.

Intention to publish date

01/08/2019

Participant level data

Not provided at time of registration

Results - basic reporting

Publication summary

Publication citations

Additional files

Editorial Notes