Evaluation of simvastatin as a disease-modifying treatment for patients with parkinson disease: a randomized clinical trial

Karen N Stevens, Siobhan Creanor, Alison Jeffrey, Alan Whone, Andy Foggo, Ben Jones, Rebecca Chapman, Laura Cocking, Jonny Wilks, Doug Webb, Camille Carroll*, PD STAT Study Group

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

2 Downloads (Pure)


Current treatments manage symptoms of Parkinson disease (PD), but no known treatment slows disease progression. Preclinical and epidemiological studies support the potential use of statins as disease-modifying therapy.

To determine whether simvastatin has potential as a disease-modifying treatment for patients with moderate PD.

Design, Setting, and Participants This randomized clinical trial, a double-blind, parallel-group, placebo-controlled futility trial, was conducted between March 2016 and May 2020 within 23 National Health Service Trusts in England. Participants aged 40 to 90 years with a diagnosis of idiopathic PD, with a modified Hoehn and Yahr stage of 3.0 or less while taking medication, and taking dopaminergic medication with wearing-off phenomenon were included. Data were analyzed from May 2020 to September 2020, with additional analysis in February 2021.

Participants were allocated 1:1 to simvastatin or matched placebo via a computer-generated random sequence, stratified by site and Hoehn and Yahr stage. In the simvastatin arm, participants entered a 1-month phase of simvastatin, 40 mg daily, followed by 23 months of simvastatin, 80 mg daily, before a 2-month washout period.

Main Outcomes and Measures The prespecified primary outcome was 24-month change in Movement Disorder Society Unified Parkinson Disease Rating Scale (MDS-UPDRS) part III score measured while not taking medication (high scores indicate worse outcome). The primary futility analysis included participants who commenced the 80-mg phase and had valid primary outcome data. The safety analysis included all participants who commenced trial treatment and is reported by dose at time of event.Results Of 332 patients assessed for eligibility, 32 declined and 65 were ineligible. Of 235 recruited participants, 97 (41%) were female, 233 (99%) were White, and the mean (SD) age was 65.4 (9.4) years. A total of 216 patients progressed to the 80-mg dose. Primary outcome analysis (n = 178) indicated the simvastatin group had an additional deterioration in MDS-UPDRS III score while not taking medication at 24 months compared with the placebo group (1.52 points; 2-sided 80% CI, −0.77 to 3.80; 1-sided futility test P = .006). A total of 37 serious adverse events (AEs), including 3 deaths, and 171 AEs were reported for participants receiving 0-mg simvastatin; 37 serious AEs and 150 AEs were reported for participants taking 40 mg or 80 mg of simvastatin. Four participants withdrew from the trial because of an AE.

Conclusions and Relevance
In this randomized clinical trial, simvastatin was futile as a disease-modifying therapy in patients with PD of moderate severity, providing no evidence to support proceeding to a phase 3 trial.

Trial Registration ISRCTN Identifier: 16108482
Original languageEnglish
Pages (from-to)1232-1241
Number of pages10
JournalJAMA Neurology
Issue number12
Early online date31 Oct 2022
Publication statusPublished - 1 Dec 2022


Dive into the research topics of 'Evaluation of simvastatin as a disease-modifying treatment for patients with parkinson disease: a randomized clinical trial'. Together they form a unique fingerprint.

Cite this