Lovastatin as a Neuroprotective Treatment for Early Stage Parkinson's Disease

• Status: Unknown status
• Trial end date: 2019-12-31
• Target enrollment: 0
• Participant gender: All

Summary

Background: Recent evidence has shown that statins, especially lipophilic statins, may have a neuroprotective benefit in Parkinson's disease (PD). We aim to perform a randomized placebo-controlled trial evaluating the disease-modifying efficacy of lovastatin in patients with early stage PD.

Methods and Study Design: This study will be a phase II, single-center, double-blind, randomized, placebo-controlled parallel-group study. In this trial, we are going to examine the possibility that lovastatin, a highly potent lipophilic statin, has disease-modifying effects in PD. We are going to enroll 80 patients with early stage PD patients. Subjects will then be randomized to a 48-week double-blind treatment period of lovastatin 80mg/day or placebo. Primary endpoints are changes in motor severity based on Movement Disorder Society-Unified Parkinson's Disease Rating Scale motor sub-score (MDS-UPDRS part III, with higher numbers indicating more severe disease). During the follow-up period, the dose of anti-parkinsonism could be added if both the patients and doctors thought the clinical condition deteriorated. Changes in PD medication as measured by levodopa-equivalent dose (LED) will be recorded at each visit. The secondary endpoints measured include MDS-UPDRS total scores, Part I and Part II sub-scores, the timing and dose of added anti-parkinsonism medication during the treatment period, the changes of 18F-DOPA PET uptake and MMSE scores, and global impression scale (GCI) of patients and investigators at the end of the study.

Expected results: We hypothesize that lovastatin would slow down both motor and cognitive symptoms deterioration and dopaminergic neuronal degeneration in patients with early stage PD.

Importance of the study: Our study will provide Class II evidence that intensive lipid lowering with lovastatin 80 mg/day decrease the disease progression in patients with early stage PD.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: National Taiwan University Hospital
• Treatments: Dihydromevinolin; L 647318; Lovastatin

Criteria

Inclusion Criteria:

• Patient is informed and given ample time and opportunity to think about his/her participation in this study and has given his/her written informed consent on an Independent Review Board (IRB) approved consent form.

• Patient is considered reliable and capable of adhering to the protocol, visit schedule, or medication administration according to the judgment of the investigator.

• Patient has a documented history of idiopathic PD consistent with the UK Parkinson's Disease Society Brain Bank Diagnostic criteria [14] prior to the Screening Visit.

• Modified Hoehn and Yahr stage =1 in the off medication state (stop medications for 1 month)

• Patients did not previously receive any anti-parkinsonism medications (drug naïve) or had stopped medications for at least 1 month.

• Age 30-90 years

Exclusion Criteria:

• Patient has any form of secondary or atypical parkinsonism (e.g., drug-induced, post stroke).

• Patient has known abnormality on brain CT or MRI imaging considered to be causing symptoms or signs of neurological dysfunction.

• Prior intracerebral surgical intervention for PD including deep brain stimulation (DBS).

• Prior or current use of statins as a lipid lowering therapy

• End stage renal disease (creatinine clearance eGFR <30 mL/min) or history of severe cardiac disease (angina, myocardial infarction or cardiac surgery in preceding two years)

• Abnormal liver function with aspartate transaminase (AST) or alanine transaminase (ALT) >2 x upper normal limit.

• Creatine kinase (CK) >2 x upper normal limit of normal.

• History of myopathy or rhabdolyolysis.

• Females who are pregnant or breast feeding.

• Patient has a history of chronic alcohol or drug abuse within the last 2 years.

• Exposure to neuroleptics (antipsychotic drugs) for more than 1 month within the past 2 years, or any exposure within the past year (except for quetiapine).