Preventing Levodopa Induced Dyskinesia in Parkinson's Disease With HMG-CoA Reductase Inhibitors

VA Office of Research and Development93 enrolled

Overview

In this study, the investigators will examine the association of statin use and dyskinesia in a convenience sample Parkinson's disease patients in the Veterans Administration Health Care System.

Long term treatment with levodopa, the gold standard treatment of Parkinson's disease (PD), can lead to the development of abnormal involuntary movements called levodopa induced dyskinesia (LID). The severity of LID can range from mild to severely debilitating. A majority of PD patients will develop LID in their treatment life-time. In a recent study of the MPTP monkey model of PD, statin use was found to reduce LID (45%) without a worsening of Parkinsonism symptoms1. Another study showed rats treated with lovastatin prior to and with initiation of levodopa after substantia nigra lesioning showed dramatically less LID evolution compared to animals without lovastatin exposure2. In this study, the investigators will examine the association of statin use and dyskinesia in a convenience sample Parkinson's disease patients in the Veterans Administration Health Care System. This study is a retrospective three cohort design and will compare statin exposure BEFORE beginning LD, versus statin exposure AFTER LD is begun, versus NO statin exposure in PD subjects controlling for disease characteristics (severity), gender, and total LD exposure The primary endpoint is the severity of LID between the groups after years of opportunity to develop LID. Levodopa-Induced dyskinesia is a major cause of reduced quality of life for Veterans with PD and, in some cases, leads to costly surgical interventions. This project examines the impact of statin use on the presence of LID, and could lead to a future intervention trial. The reduction, delayed onset, or elimination of LID could improve the quality of life of many Veterans nationwide.

Study Type

OBSERVATIONAL

Enrollment

Conditions

Parkinson Disease Dyskinesia, Drug-Induced

Interventions

Intravenous InfusionDRUG

Intravenous levodopa given 1.0 to 1.5 mg/kg/hr from 0930 - 1130 on a single visit day.

Eligibility

Sex: ALLMin age: 50 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Parkinson's Disease * Age diagnosed with Parkinson's Disease greater than or equal to 50 years * Treatment with levodopa greater than or equal to 5 years Exclusion Criteria: * Deep Brain stimulation * Unable to stand for 1 minute intervals, or sensory deficits in the feet * Significant cognitive impairment as measured by the Montreal Cognitive Assessment score of \< 18 * Subjects with unstable medical or psychiatric conditions (including hallucinations). * History of unstable medical conditions (i.e. active cardiac disease, recent unwellness, surgery etc.) * Current use of drugs that may affect parkinsonism or dyskinesia: * dopamine receptor blocking medications * depakote * lithium * amiodarone * tetrabenazine * metoclopramide * dronabinol * and illicit drugs such as marijuana (THC) * cocaine * methamphetamine * Statins other than simvastatin or lovastatin, atorvastatin ie. fluvastatin (rationale is that while all other statins are thought to not cross the blood brain barrier well, the central nervous system penetrating nature of others is not perfectly clear and could confound results)

Locations (3)

VA Portland Health Care System, Portland, OR

Portland, Oregon, United States

Oregon Health & Science University

Portland, Oregon, United States

VA Puget Sound Health Care System Seattle Division, Seattle, WA

Seattle, Washington, United States

Outcomes

Primary Outcomes

Peak Unified Dyskinesia Rating Score (UDysRS)

The Unified Dyskinesia Rating Scale (UDysRS) combines patient, caregiver, and treating physician perspectives on both historical (Parts 1 \& 2) and objective (Part 3 \& 4) assessments of dyskinesia and dystonia. The historical portion and the objective ratings are added together to form total score ranging from 0 to 104 with higher scores indicating more severe dyskinesia.

Time frame: 11:00 am

Secondary Outcomes

Peak Unified Dyskinesia Rating Scale - Objective Measures

The Unified Dyskinesia Rating Scale (UDysRS) objective (Part 3 \& 4) assessments of dyskinesia and dystonia. The objective ratings are added together to form total score ranging from 0 to 44 with higher scores indicating more severe dyskinesia.

Time frame: 11:00 am

Presence/Absence of Levodopa-induced Dyskinesia (LID).

Any score greater than or equal to 1 on the Clinical Dyskinesia Rating Scale (CDRS) during the intravenous levodopa cycle from 0900 - 1500. The CDRS is a commonly utilized scale that is completed by an observer who judges the severity of LID (0-4) in 7 body parts (face, neck, trunk, both legs, and both arms) during as the subject performs the cognitive distraction task while standing on the force plate for 60 seconds. CDRS ratings are made every half hour during the LD dose cycle by the principal investigator (KC) or co-investigator.

Time frame: Every half hour from 0900 to 1500

Clinical Dyskinesia Rating Scale (Peak)

The Clinical Dyskinesia Rating Scale (CDRS) is a commonly utilized scale that is completed by an observer who judges the severity of Levodopa induced dyskinesia (LID) in 7 body parts (face, neck, trunk, both legs, and both arms) during the force plate stance with a cognitive distraction task for 60 seconds. All body parts are rated separately on this 0 (none) to 4 (severe - markedly impairs activities) scale. Thus, the total score can range from 0 - 28 with 28 indicating the most severe LID. Peak CDRS ratings are the 11:00 am ratings.

Data from ClinicalTrials.gov

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