Preventing Levodopa Induced Dyskinesia in Parkinson's Disease With HMG-CoA Reductase Inhibitors (STAT-PD)

Preventing Levodopa Induced Dyskinesia in Parkinson's Disease With Statins

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.

Study Overview

• Status: Completed
• Conditions: Parkinson Disease; Dyskinesia, Drug-Induced
• Intervention / Treatment: Drug: Intravenous Infusion

Detailed Description

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 (Actual): 93

Contacts and Locations

Study Locations

• United States
  • Oregon
    • Portland, Oregon, United States, 97207-2964
      • VA Portland Health Care System, Portland, OR
    • Portland, Oregon, United States, 97239not
      • Oregon Health & Science University
  • Washington
    • Seattle, Washington, United States, 98108
      • VA Puget Sound Health Care System Seattle Division, Seattle, WA

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 46 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Parkinson's Disease

Description

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)

Study Plan

How is the study designed?

Design Details

• Observational Models: Case-Control
• Time Perspectives: Retrospective

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Statin Before Levodopa; Historical use of a statin BEFORE beginning levodopa	Drug: Intravenous Infusion; Intravenous levodopa given 1.0 to 1.5 mg/kg/hr from 0930 - 1130 on a single visit day.; Other Names: levodopa
Statin After Levodopa; Historical use of a statin AFTER beginning levodopa	Drug: Intravenous Infusion; Intravenous levodopa given 1.0 to 1.5 mg/kg/hr from 0930 - 1130 on a single visit day.; Other Names: levodopa
No Statin; No historical use of a statin	Drug: Intravenous Infusion; Intravenous levodopa given 1.0 to 1.5 mg/kg/hr from 0930 - 1130 on a single visit day.; Other Names: levodopa

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	11:00 am

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	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.	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.	11:00 am

Collaborators and Investigators

• Sponsor: VA Office of Research and Development
• Collaborators: Oregon Health and Science University
• Investigators: Principal Investigator: Kathryn Anne Chung, MD, VA Portland Health Care System, Portland, OR

Publications and helpful links

General Publications

• Obeso JA, Rodriguez-Oroz MC, Rodriguez M, DeLong MR, Olanow CW. Pathophysiology of levodopa-induced dyskinesias in Parkinson's disease: problems with the current model. Ann Neurol. 2000 Apr;47(4 Suppl 1):S22-32; discussion S32-4.
• Tison F, Negre-Pages L, Meissner WG, Dupouy S, Li Q, Thiolat ML, Thiollier T, Galitzky M, Ory-Magne F, Milhet A, Marquine L, Spampinato U, Rascol O, Bezard E. Simvastatin decreases levodopa-induced dyskinesia in monkeys, but not in a randomized, placebo-controlled, multiple cross-over ("n-of-1") exploratory trial of simvastatin against levodopa-induced dyskinesia in Parkinson's disease patients. Parkinsonism Relat Disord. 2013 Apr;19(4):416-21. doi: 10.1016/j.parkreldis.2012.12.003. Epub 2012 Dec 31.
• Pavon N, Martin AB, Mendialdua A, Moratalla R. ERK phosphorylation and FosB expression are associated with L-DOPA-induced dyskinesia in hemiparkinsonian mice. Biol Psychiatry. 2006 Jan 1;59(1):64-74. doi: 10.1016/j.biopsych.2005.05.044. Epub 2005 Sep 1.

Study record dates

Study Major Dates

• Study Start (Actual): August 22, 2019
• Primary Completion (Actual): March 31, 2024
• Study Completion (Actual): March 31, 2024

Study Registration Dates

• First Submitted: August 19, 2019
• First Submitted That Met QC Criteria: August 19, 2019
• First Posted (Actual): August 21, 2019

Study Record Updates

• Last Update Posted (Actual): April 11, 2025
• Last Update Submitted That Met QC Criteria: April 10, 2025
• Last Verified: April 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Synucleinopathies; Neurologic Manifestations; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurodegenerative Diseases; Chemically-Induced Disorders; Movement Disorders; Drug-Related Side Effects and Adverse Reactions; Poisoning; Parkinsonian Disorders; Basal Ganglia Diseases; Neurotoxicity Syndromes; Dyskinesias; Parkinson Disease; Dyskinesia, Drug-Induced; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Neurotransmitter Agents; Dopamine Agents; Antiparkinson Agents; Anti-Dyskinesia Agents; Levodopa
• Other Study ID Numbers: NURE-004-18S; 17302 (Other Grant/Funding Number: Oregon Health and Science University); 3869 (Other Identifier: VA Portland Health Care System); 5273 (Other Identifier: Oregon Clinical & Translational Research Institute); 1635227 (Other Identifier: VA Portland Health Care System (IRBNet))

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Individual participant data be available (including data dictionaries). Individual participant data that underlie the results reported the resultant article, after deidentification (text, tables, figures, and appendices). In addition to data, the study protocol and the informed consent form (ICF) will be provided. Data will be available beginning 6 months and ending 2 years following article publication. Data will be shared with Investigators whose proposed use of the data has been approved by an independent review committee ("learned intermediary") identified for this purpose. Data will be released to achieve aims in the approved proposal or for individual participant data meta-analysis. Proposals may be submitted up to 24 months following article publication. After 24 months the data will be available in the investigators' VA'S data repository but without investigator support other than deposited metadata.
• IPD Sharing Time Frame: beginning 5 months and ending 2 years following article publication.
• IPD Sharing Access Criteria: Data will be shared with Investigators whose proposed use of the data has been approved by an independent review committee ("learned intermediary") identified for this purpose.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; ICF

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No