A trial comparing simvastatin to placebo as a neuronal protective treatment for Parkinson's disease.

• Register: EUCTR
• Last refreshed on: 19 October 2020
• Main ID: EUCTR2015-000148-40-GB
• Date of registration: 16/09/2015
• Prospective Registration: Yes
• Primary sponsor: Plymouth Hospitals NHS Trust
• Public title: A trial comparing simvastatin to placebo as a neuronal protective treatment for Parkinson's disease.
• Scientific title: Simvastatin as a neuroprotective treatment for Parkinson's disease: a double-blind, randomised, placebo controlled futility study in patients of moderate severity. - Simvastatin as a neuroprotective treatment for moderate PD (PD STAT)
• Date of first enrolment: 09/11/2015
• Target sample size: 198
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2015-000148-40
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes; Randomised: yes; Open: no; Single blind: no; Double blind: no; Parallel group: no; Cross over: no; Other: no; If controlled, specify comparator, Other Medicinial Product: no; Placebo: yes; Other: no; Number of treatment arms in the trial: 2
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

United Kingdom

Contacts

• Name: Vickers
• Affiliation: Plymouth Hospitals NHS Trust

• Name: Vickers
• Affiliation: Plymouth Hospitals NHS Trust

Key inclusion & exclusion 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
Are the trial subjects under 18? no
Number of subjects for this age range: 0
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 150
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 48

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
• Any requirement for statin use
• Regular participation in endurance or high-impact sports
• Unable to abstain from consumption of grapefruit-based products


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Parkinson's disease
MedDRA version: 18.0 Level: PT Classification code 10061536 Term: Parkinson's disease System Organ Class: 10029205 - Nervous system disorders
MedDRA version: 18.0 Level: LLT Classification code 10013113 Term: Disease Parkinson's System Organ Class: 10029205 - Nervous system disorders

Therapeutic area: Diseases [C] - Nervous System Diseases [C10]

Intervention(s)

Product Name: Simvastatin
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: Simvastatin
CAS Number: 79902-63-9
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 40-
Pharmaceutical form of the placebo: Capsule, soft
Route of administration of the placebo: Oral use

Primary Outcome(s)

Secondary Objective: To confirm the safety and tolerability of simvastatin in patients with PD.
To distinguish symptomatic effects of simvastatin from disease modifying effects.
To evaluate the impact of simvastatin on activities of daily living (ADL), timed motor tests, cognitive ability, mood, behaviour, non-motor symptoms (NMS) and quality of life among patients with moderate PD using standard validated tools of assessment.

Primary end point(s): A change in MDS-UPDRS (Movement Disorder Society Unified Parkinson's disease Rating Scale) part III motor subscale score in the OFF state over 24 months.

Main Objective: To determine whether simvastatin is clearly ineffective (futile) in preventing the clinical decline of PD as measured by the Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS) motor score.

Timepoint(s) of evaluation of this end point: 24 months.

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: At 12 and 24 months

Secondary end point(s): - MDS-UPDRS total score in the practically defined ON state
- MDS-UPDRS part II subscale score in the practically defined ON state
- Timed motor tests – finger tapping and timed walk test (10MWT) in the OFF state
- Montgomery and Asberg Depression Rating Scale (MADRS)
- The Addenbrooke’s Cognitive Assessment-III (ACE-III)
- Non-Motor Symptom assessment scale (NMSS)
- Parkinson’s disease Questionnaire (PDQ-39)
- Changes in PD medication as measured by levodopa-equivalent dose (LED)
- Cholesterol levels (total, HDL, LDL, total/HDL ratio)
- King’s PD pain scale (KPPS)
- EuroQoL 5D-5L health status questionnaire (EQ-5D-5L)
- Safety and tolerability of trial medication by adverse events (AEs) review.
- Incidence of diabetes mellitus at 24 months (using a Glycated haemoglobin (HbA1c) level of 6.5% (48mmol/mol) as diagnostic of diabetes mellitus (WHO 2011: http://www.who.int/diabetes/publications/report-hba1c_2011.pdf)

Secondary ID(s)

PDSTAT2015

15/NE/0324

Ethics review

Status: Approved
Approval date: 12/10/2015
Contact: