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Simvastatin as a Neuroprotective Treatment for Moderate Parkinson's Disease (PD STAT)

Primary Purpose

Parkinson Disease

Status
Completed
Phase
Phase 2
Locations
United Kingdom
Study Type
Interventional
Intervention
Simvastatin
Matched Placebo (for Simvastatin)
Sponsored by
University Hospital Plymouth NHS Trust
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Parkinson Disease focused on measuring Neurology

Eligibility Criteria

40 Years - 90 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Royal United Hospital
  • Royal Bournemouth Hospital
  • Fairfield General Hospital
  • Addenbrooke's Hospital
  • St Peter's Hospital
  • Royal Devon and Exeter Hospital
  • Leeds General Infirmary
  • Charing Cross Hospital
  • King's College Hospital
  • Royal Free Hospital
  • Luton and Dunstable Hospital
  • Clinical Ageing Research Unit
  • Norfolk and Norwich University Hospital
  • John Radcliffe Hospital
  • Derriford Hospital
  • Royal Preston Hospital
  • Queen's Hospital
  • Rotherham General Hospital
  • Salford Royal Hospital
  • Royal Hallamshire Hospital
  • Royal Stoke University Hospital
  • Musgrove Park Hospital
  • Royal Cornwall Hospital
  • Yeovil District Hospital

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Placebo Comparator

Arm Label

Simvastatin

Matched Placebo

Arm Description

A one month low dose phase of 40mg oral simvastatin daily will be followed by a 23 month high dose phase of 80mg oral simvastatin daily and a final two month phase off trial medication

A one month low dose phase of 40mg matched placebo daily will be followed by a 23 month high dose phase of 80mg matched placebo daily and a final two month phase off trial medication

Outcomes

Primary Outcome Measures

Change in MDS-UPDRS part III (OFF) score
The MDS-UPDRS is the standard validated tool for the assessment of patients with Parkinson's Disease. This scale includes subsections collecting data regarding the impact of PD on a patient's mood and mental state, (UPDRS part I), their activities of daily living (UPDRS part II) an examination of the motor features of PD (UPDRS part III), and complications arising from the use of dopamine replacement (part IV).

Secondary Outcome Measures

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, electromagnetic sensor (EMS) assessment in the OFF and ON state
Timed Motor Tests include evaluating the number of hand taps (key strokes) that an individual can perform within 30 seconds and a timed walk test (10MWT). Electromagnetic Sensor Measurements include wearing sensors on the index finger and thumb whilst performing 4 MDS-UPDRS items.
Montgomery and Asberg Depression Rating Scale (MADRS)
The Montgomery and Asberg Depression Rating Scale (MADRS) is a 10 item physician rated depression severity scale previously used in the assessment of PD
The Addenbrooke's Cognitive Assessment-III (ACE-III)
The Addenbrooke's Cognitive Examination-III (ACE) is one of the most popular and PD STAT protocol version 2.2, 03 March 2016 EudraCT 2015-000148-40 ISRCTN16108482. REC Ref:15/NE/0324 Page 39 of 43 commonly used cognitive tests used in dementia clinics and in the assessment of other neurological disorders. ACE-III includes five subdomains which provide a cognitive score out of a maximum of 100
Non-Motor Symptom assessment scale (NMSS)
The Non-Motor Symptom assessment scale (NMSS) is a rating scale designed to capture the presence of the non-motor features of PD
Parkinson's disease Questionnaire (PDQ-39)
The PDQ39 is a PD-specific health status questionnaire used both clinically and within research since its publication in 1995. It consists of 39 items covering eight discrete dimensions: mobility, emotional well-being, stigma, social support, cognition, communication and bodily discomfort. The scores from each dimension are computed into a scale ranging from 0 (best, i.e. no problem at all) to 100 (worst, i.e. maximum level of problem). In addition a summary score, the PDQ-39SI (summary index) can be calculated by averaging the scores of the eight dimensions.
Changes in PD medication as measured by levodopa-equivalent dose (LED)
Cholesterol levels (total, HDL, total/HDL ratio)
King's PD pain scale (KPPS)
The King's PD Pain Scale is a PD-specific scale consisting of 14 items within seven domains. Each item is scored by severity (0-3) multiplied by frequency (0-4), resulting in an item sub-score of 0-12 and a total possible score of 0-168.
EuroQoL 5D-5L health status questionnaire (EQ-5D-5L)
Safety and tolerability of trial medication by adverse events (AEs) review.
Incidence of diabetes mellitus, using a glycated haemoglobin (HbA1c) level of 6.5% (48mmol/mol) as diagnostic of diabetes mellitus.

Full Information

First Posted
May 26, 2016
Last Updated
October 8, 2021
Sponsor
University Hospital Plymouth NHS Trust
Collaborators
University of Plymouth
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1. Study Identification

Unique Protocol Identification Number
NCT02787590
Brief Title
Simvastatin as a Neuroprotective Treatment for Moderate Parkinson's Disease
Acronym
PD STAT
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

2. Study Status

Record Verification Date
October 2021
Overall Recruitment Status
Completed
Study Start Date
March 8, 2016 (Actual)
Primary Completion Date
November 1, 2019 (Actual)
Study Completion Date
December 31, 2020 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University Hospital Plymouth NHS Trust
Collaborators
University of Plymouth

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Parkinson Disease
Keywords
Neurology

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
235 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Simvastatin
Arm Type
Active Comparator
Arm Description
A one month low dose phase of 40mg oral simvastatin daily will be followed by a 23 month high dose phase of 80mg oral simvastatin daily and a final two month phase off trial medication
Arm Title
Matched Placebo
Arm Type
Placebo Comparator
Arm Description
A one month low dose phase of 40mg matched placebo daily will be followed by a 23 month high dose phase of 80mg matched placebo daily and a final two month phase off trial medication
Intervention Type
Drug
Intervention Name(s)
Simvastatin
Intervention Type
Drug
Intervention Name(s)
Matched Placebo (for Simvastatin)
Primary Outcome Measure Information:
Title
Change in MDS-UPDRS part III (OFF) score
Description
The MDS-UPDRS is the standard validated tool for the assessment of patients with Parkinson's Disease. This scale includes subsections collecting data regarding the impact of PD on a patient's mood and mental state, (UPDRS part I), their activities of daily living (UPDRS part II) an examination of the motor features of PD (UPDRS part III), and complications arising from the use of dopamine replacement (part IV).
Time Frame
Baseline and 24 Months
Secondary Outcome Measure Information:
Title
MDS-UPDRS total score in the practically defined ON state
Time Frame
at 12 and 24 months
Title
MDS-UPDRS part II subscale score in the practically defined ON state
Time Frame
at 12 and 24 months
Title
Timed motor tests - finger tapping and timed walk test (10MWT) in the OFF state, electromagnetic sensor (EMS) assessment in the OFF and ON state
Description
Timed Motor Tests include evaluating the number of hand taps (key strokes) that an individual can perform within 30 seconds and a timed walk test (10MWT). Electromagnetic Sensor Measurements include wearing sensors on the index finger and thumb whilst performing 4 MDS-UPDRS items.
Time Frame
at 12 and 24 months
Title
Montgomery and Asberg Depression Rating Scale (MADRS)
Description
The Montgomery and Asberg Depression Rating Scale (MADRS) is a 10 item physician rated depression severity scale previously used in the assessment of PD
Time Frame
at 12 and 24 months
Title
The Addenbrooke's Cognitive Assessment-III (ACE-III)
Description
The Addenbrooke's Cognitive Examination-III (ACE) is one of the most popular and PD STAT protocol version 2.2, 03 March 2016 EudraCT 2015-000148-40 ISRCTN16108482. REC Ref:15/NE/0324 Page 39 of 43 commonly used cognitive tests used in dementia clinics and in the assessment of other neurological disorders. ACE-III includes five subdomains which provide a cognitive score out of a maximum of 100
Time Frame
at 12 and 24 months
Title
Non-Motor Symptom assessment scale (NMSS)
Description
The Non-Motor Symptom assessment scale (NMSS) is a rating scale designed to capture the presence of the non-motor features of PD
Time Frame
at 12 and 24 months
Title
Parkinson's disease Questionnaire (PDQ-39)
Description
The PDQ39 is a PD-specific health status questionnaire used both clinically and within research since its publication in 1995. It consists of 39 items covering eight discrete dimensions: mobility, emotional well-being, stigma, social support, cognition, communication and bodily discomfort. The scores from each dimension are computed into a scale ranging from 0 (best, i.e. no problem at all) to 100 (worst, i.e. maximum level of problem). In addition a summary score, the PDQ-39SI (summary index) can be calculated by averaging the scores of the eight dimensions.
Time Frame
at 12 and 24 months
Title
Changes in PD medication as measured by levodopa-equivalent dose (LED)
Time Frame
at 12 and 24 months
Title
Cholesterol levels (total, HDL, total/HDL ratio)
Time Frame
at 12 and 24 months
Title
King's PD pain scale (KPPS)
Description
The King's PD Pain Scale is a PD-specific scale consisting of 14 items within seven domains. Each item is scored by severity (0-3) multiplied by frequency (0-4), resulting in an item sub-score of 0-12 and a total possible score of 0-168.
Time Frame
at 12 and 24 months
Title
EuroQoL 5D-5L health status questionnaire (EQ-5D-5L)
Time Frame
at 12 and 24 months
Title
Safety and tolerability of trial medication by adverse events (AEs) review.
Time Frame
at 12 and 24 months
Title
Incidence of diabetes mellitus, using a glycated haemoglobin (HbA1c) level of 6.5% (48mmol/mol) as diagnostic of diabetes mellitus.
Time Frame
at 24 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
40 Years
Maximum Age & Unit of Time
90 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Camille B Carroll, BM BCh, PhD
Organizational Affiliation
Clinical Lecturer (University of Plymouth) and Honorary Consultant Neurologist, Plymouth Hospitals NHS Trust.
Official's Role
Study Director
Facility Information:
Facility Name
Royal United Hospital
City
Bath
Country
United Kingdom
Facility Name
Royal Bournemouth Hospital
City
Bournemouth
Country
United Kingdom
Facility Name
Fairfield General Hospital
City
Bury
Country
United Kingdom
Facility Name
Addenbrooke's Hospital
City
Cambridge
Country
United Kingdom
Facility Name
St Peter's Hospital
City
Chertsey
Country
United Kingdom
Facility Name
Royal Devon and Exeter Hospital
City
Exeter
Country
United Kingdom
Facility Name
Leeds General Infirmary
City
Leeds
Country
United Kingdom
Facility Name
Charing Cross Hospital
City
London
Country
United Kingdom
Facility Name
King's College Hospital
City
London
Country
United Kingdom
Facility Name
Royal Free Hospital
City
London
Country
United Kingdom
Facility Name
Luton and Dunstable Hospital
City
Luton
Country
United Kingdom
Facility Name
Clinical Ageing Research Unit
City
Newcastle
Country
United Kingdom
Facility Name
Norfolk and Norwich University Hospital
City
Norwich
Country
United Kingdom
Facility Name
John Radcliffe Hospital
City
Oxford
Country
United Kingdom
Facility Name
Derriford Hospital
City
Plymouth
Country
United Kingdom
Facility Name
Royal Preston Hospital
City
Preston
Country
United Kingdom
Facility Name
Queen's Hospital
City
Romford
Country
United Kingdom
Facility Name
Rotherham General Hospital
City
Rotherham
Country
United Kingdom
Facility Name
Salford Royal Hospital
City
Salford
Country
United Kingdom
Facility Name
Royal Hallamshire Hospital
City
Sheffield
Country
United Kingdom
Facility Name
Royal Stoke University Hospital
City
Stoke-on-Trent
Country
United Kingdom
Facility Name
Musgrove Park Hospital
City
Taunton
Country
United Kingdom
Facility Name
Royal Cornwall Hospital
City
Truro
Country
United Kingdom
Facility Name
Yeovil District Hospital
City
Yeovil
Country
United Kingdom

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing Plan Description
The data sharing plans for the current study are unknown and will be made available at a later date
IPD Sharing Time Frame
On application
Citations:
PubMed Identifier
31594876
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.
Results Reference
derived
Links:
URL
https://penctu.psmd.plymouth.ac.uk/pdstat/Default.aspx
Description
Trial website

Learn more about this trial

Simvastatin as a Neuroprotective Treatment for Moderate Parkinson's Disease

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