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

NCT ID: NCT04064294

Last Updated: 2025-04-11

Basic Information

• Recruitment Status: COMPLETED
• Total Enrollment: 93 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2019-08-22
• Study Completion Date: 2024-03-31

Brief Summary

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.

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.

Conditions

Parkinson Disease; Dyskinesia, Drug-Induced

Study Design

• Observational Model Type: CASE_CONTROL
• Study Time Perspective: RETROSPECTIVE

Study Groups

Statin Before Levodopa

Historical use of a statin BEFORE beginning levodopa

Intravenous Infusion

Intervention Type: DRUG

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

Statin After Levodopa

Historical use of a statin AFTER beginning levodopa

Intravenous Infusion

Intervention Type: DRUG

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

No Statin

No historical use of a statin

Intravenous Infusion

Intervention Type: DRUG

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

Interventions

Intravenous Infusion

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

Intervention Type: DRUG

Other Intervention Names

levodopa

Eligibility Criteria

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)

• Minimum Eligible Age: 50 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Oregon Health and Science University

OTHER

Sponsor Role: collaborator

VA Office of Research and Development

FED

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Kathryn Anne Chung, MD

Role: PRINCIPAL_INVESTIGATOR

VA Portland Health Care System, Portland, OR

Locations

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

Countries

United States

References

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.

Reference Type: BACKGROUND

PMID: 10762129 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 23283428 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 16139809 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Document Type: Informed Consent Form

View Document

Other Identifiers

17302

Identifier Type: OTHER_GRANT

Identifier Source: secondary_id

3869

Identifier Type: OTHER

Identifier Source: secondary_id

5273

Identifier Type: OTHER

Identifier Source: secondary_id

1635227

Identifier Type: OTHER

Identifier Source: secondary_id

NURE-004-18S

Identifier Type: -

Identifier Source: org_study_id