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

Completed

Conditions: Dyskinesia, Drug-Induced
Parkinson Disease

Interventions: Drug: Intravenous Infusion

Registration Number: NCT04064294

Lead Sponsor: VA Office of Research and Development

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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 93

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 & Design

Study Type: OBSERVATIONAL

Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Statin After Levodopa	Intravenous Infusion	Historical use of a statin AFTER beginning levodopa
No Statin	Intravenous Infusion	No historical use of a statin
Statin Before Levodopa	Intravenous Infusion	Historical use of a statin BEFORE beginning levodopa

Primary Outcome Measures

Name	Time	Method
Peak Unified Dyskinesia Rating Score (UDysRS)	11:00 am	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.

Secondary Outcome Measures

Name	Time	Method
Peak Unified Dyskinesia Rating Scale - Objective Measures	11:00 am	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.
Presence/Absence of Levodopa-induced Dyskinesia (LID).	Every half hour from 0900 to 1500	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.
Clinical Dyskinesia Rating Scale (Peak)	11:00 am	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.

Trial Locations

Locations (3): VA Portland Health Care System, Portland, OR
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Portland, Oregon, United States
Oregon Health & Science University
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Portland, Oregon, United States
VA Puget Sound Health Care System Seattle Division, Seattle, WA
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Seattle, Washington, United States