Simvastatin as a neuroprotective treatment for moderate Parkinson's disease
| ISRCTN | ISRCTN16108482 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN16108482 |
| EudraCT/CTIS number | 2015-000148-40 |
| ClinicalTrials.gov number | NCT02787590 |
| Secondary identifying numbers | CPMS 19666 |
- Submission date
- 19/11/2015
- Registration date
- 19/11/2015
- Last edited
- 21/12/2023
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Nervous System Diseases
Plain English summary of protocol
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
Contact information
Public
Peninsula Clinical Trials Unit
Plymouth University Peninsula Schools of Medicine and Dentistry
Room N16
ITTC Building 1
Plymouth Science Park
Plymouth
PL6 8BX
United Kingdom
Study information
| Study design | Double-blind placebo-controlled multi-centre randomized futility study |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Randomised controlled trial |
| Study setting(s) | Hospital |
| Study type | Treatment |
| Participant information sheet | Not available in web format, please use the contact details to request a participant information sheet |
| Scientific title | Simvastatin as a neuroprotective treatment for Parkinson's disease: a double-blind, randomised, placebo-controlled futility study in patients of moderate severity |
| Study acronym | PD STAT |
| Study objectives | 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(s) | Newcastle and North Tyneside 2 Research Ethics Committee, 12/10/2015, ref: 15/NE/0324 |
| Health condition(s) or problem(s) studied | 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 |
| Pharmaceutical study type(s) | |
| Phase | Not Applicable |
| Drug / device / biological / vaccine name(s) | 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 study start date | 01/01/2015 |
| Completion date | 30/09/2020 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Lower age limit | 40 Years |
| Upper age limit | 90 Years |
| Sex | Both |
| Target number of participants | Planned Sample Size: 198; UK Sample Size: 198 |
| Total final enrolment | 235 |
| Key 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 |
| Key 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 |
| Date of first enrolment | 01/12/2015 |
| Date of final enrolment | 31/03/2018 |
Locations
Countries of recruitment
- England
- United Kingdom
Study participating centres
Treliske
Cornwall
TR1 3LQ
United Kingdom
Plymouth
PL6 8DH
United Kingdom
Taunton
TA1 5DA
United Kingdom
Yeovil
BA21 4AT
United Kingdom
Christchurch
BH23 2JX
United Kingdom
Bath
BA1 3NG
United Kingdom
Chertsey
KT16 0PZ
United Kingdom
London
W6 8RF
United Kingdom
London
NW3 2QG
United Kingdom
Romford
RM7 0AG
United Kingdom
Oxford
OX3 9DU
United Kingdom
Lewsey Road
Luton
LU4 0DZ
United Kingdom
Cambridge
CB2 0QQ
United Kingdom
Salford
M6 8HD
United Kingdom
Bury
BL9 7TD
United Kingdom
Preston
PR2 9HT
United Kingdom
Leeds
LS1 3EX
United Kingdom
Newcastle upon Tyne
NE4 5PL
United Kingdom
Exeter
EX2 5DW
United Kingdom
Brixton
London
SE5 9RS
United Kingdom
Sheffield
S10 2JF
United Kingdom
Norwich
NR4 7UY
United Kingdom
Rotherham
S60 2UD
United Kingdom
Stoke-on-Trent
ST4 6QG
United Kingdom
Sponsor information
Hospital/treatment centre
Research Office
Level 2
MSCP
Bircham Park Offices
Morlaix Drive
Plymouth
PL6 8BQ
England
United Kingdom
"ROR" |
https://ror.org/05x3jck08 |
|---|
Funders
Funder type
Charity
No information available
No information available
Results and Publications
| Intention to publish date | 30/06/2022 |
|---|---|
| Individual participant data (IPD) Intention to share | No |
| IPD sharing plan summary | Stored in repository |
| 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 plan | The researchers intend to deposit anonymised patient-level data in the Critical Path for Parkinson’s Consortium. |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Protocol article | protocol | 07/10/2019 | 23/07/2020 | Yes | No |
| Statistical Analysis Plan | 24/08/2020 | 07/01/2022 | No | No | |
| Basic results | 03/06/2021 | 16/06/2022 | No | No | |
| Results article | 31/10/2022 | 01/11/2022 | Yes | No | |
| HRA research summary | 28/06/2023 | No | No | ||
| Protocol (other) | 31/10/2022 | 21/12/2023 | No | No | |
| Statistical Analysis Plan | 31/10/2022 | 21/12/2023 | No | No |
Editorial Notes
21/12/2023: Protocol and statistical analysis plan added.
01/11/2022: Publication reference added.
16/06/2022: EU Clinical Trials Register results added.
28/03/2022: The intention to publish date was changed from 30/09/2021 to 30/06/2022.
07/01/2022: Publication reference added.
03/09/2020: The intention to publish date was changed from 01/10/2020 to 30/09/2021.
10/08/2020: Total final enrolment number and IPD sharing statement added.
23/07/2020: Publication reference added.
10/04/2018: The following changes were made to the trial record:
1. The contact details were updated.
2. ClinicalTrials.gov number added.
3. The recruitment end date was changed from 01/12/2016 to 31/03/2018.
4. The overall trial end date was changed from 31/12/2018 to 30/09/2020.
5. The trial participating centres were updated to remove North Devon District Hospital and Frenchay Hospital and add Royal Devon and Exeter Hospital, King's College Hospital, Royal Hallamshire Hospital, Norfolk and Norwich University Hospital, Rotherham General Hospital and Royal Stoke University Hospital.
6. The intention to publish date was changed from 01/08/2019 to 01/10/2020.
7. IPD sharing statement added.
