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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02787590
Recruitment Status : Active, not recruiting
First Posted : June 1, 2016
Last Update Posted : June 1, 2020
Sponsor:
Collaborator:
University of Plymouth
Information provided by (Responsible Party):
University Hospital Plymouth NHS Trust

Tracking Information
First Submitted Date  ICMJE May 26, 2016
First Posted Date  ICMJE June 1, 2016
Last Update Posted Date June 1, 2020
Actual Study Start Date  ICMJE March 21, 2016
Estimated Primary Completion Date June 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 31, 2016)
Change in MDS-UPDRS part III (OFF) score [ Time Frame: Baseline and 24 Months ]
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).
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: November 30, 2017)
  • MDS-UPDRS total score in the practically defined ON state [ Time Frame: at 12 and 24 months ]
  • MDS-UPDRS part II subscale score in the practically defined ON state [ Time Frame: at 12 and 24 months ]
  • Timed motor tests - finger tapping and timed walk test (10MWT) in the OFF state, electromagnetic sensor (EMS) assessment in the OFF and ON state [ Time Frame: at 12 and 24 months ]
    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) [ Time Frame: at 12 and 24 months ]
    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) [ Time Frame: at 12 and 24 months ]
    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) [ Time Frame: at 12 and 24 months ]
    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) [ Time Frame: at 12 and 24 months ]
    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) [ Time Frame: at 12 and 24 months ]
  • Cholesterol levels (total, HDL, total/HDL ratio) [ Time Frame: at 12 and 24 months ]
  • King's PD pain scale (KPPS) [ Time Frame: at 12 and 24 months ]
    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) [ Time Frame: at 12 and 24 months ]
  • Safety and tolerability of trial medication by adverse events (AEs) review. [ Time Frame: at 12 and 24 months ]
  • 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 ]
Original Secondary Outcome Measures  ICMJE
 (submitted: May 31, 2016)
  • MDS-UPDRS total score in the practically defined ON state [ Time Frame: at 12 and 24 months ]
  • MDS-UPDRS part II subscale score in the practically defined ON state [ Time Frame: at 12 and 24 months ]
  • Timed motor tests - finger tapping and timed walk test (10MWT) in the OFF state [ Time Frame: at 12 and 24 months ]
    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).
  • Montgomery and Asberg Depression Rating Scale (MADRS) [ Time Frame: at 12 and 24 months ]
    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) [ Time Frame: at 12 and 24 months ]
    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) [ Time Frame: at 12 and 24 months ]
    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) [ Time Frame: at 12 and 24 months ]
    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) [ Time Frame: at 12 and 24 months ]
  • Cholesterol levels (total, HDL, total/HDL ratio) [ Time Frame: at 12 and 24 months ]
  • King's PD pain scale (KPPS) [ Time Frame: at 12 and 24 months ]
    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) [ Time Frame: at 12 and 24 months ]
  • Safety and tolerability of trial medication by adverse events (AEs) review. [ Time Frame: at 12 and 24 months ]
  • 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 ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Simvastatin as a Neuroprotective Treatment for Moderate Parkinson's Disease
Official Title  ICMJE Simvastatin as a Neuroprotective Treatment for Parkinson's Disease: a Double-blind, Randomised, Placebo Controlled Futility Study in Patients of Moderate Severity.
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.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE Parkinson Disease
Intervention  ICMJE
  • Drug: Simvastatin
  • Drug: Matched Placebo (for Simvastatin)
Study Arms  ICMJE
  • Active Comparator: Simvastatin
    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
    Intervention: Drug: Simvastatin
  • Placebo Comparator: Matched Placebo
    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: Drug: Matched Placebo (for Simvastatin)
Publications * 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.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Actual Enrollment  ICMJE
 (submitted: April 11, 2018)
235
Original Estimated Enrollment  ICMJE
 (submitted: May 31, 2016)
198
Estimated Study Completion Date  ICMJE August 2020
Estimated Primary Completion Date June 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 40 Years to 90 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United Kingdom
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02787590
Other Study ID Numbers  ICMJE PDSTAT2015
2015-000148-40 ( EudraCT Number )
16108482 ( Registry Identifier: ISRCTN )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD: Undecided
Plan Description: The data sharing plans for the current study are unknown and will be made available at a later date
Responsible Party University Hospital Plymouth NHS Trust
Study Sponsor  ICMJE University Hospital Plymouth NHS Trust
Collaborators  ICMJE University of Plymouth
Investigators  ICMJE
Study Director: Camille B Carroll, BM BCh, PhD Clinical Lecturer (University of Plymouth) and Honorary Consultant Neurologist, Plymouth Hospitals NHS Trust.
PRS Account University Hospital Plymouth NHS Trust
Verification Date May 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP