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

Parkinson Disease Clinical Trial

— STAT-PD  

Official title:

Preventing Levodopa Induced Dyskinesia in Parkinson?s Disease With Statins

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04064294
• Other study ID #: NURE-004-18S
• Secondary ID: 1730238695273163
• Status: Recruiting
• Start date: June 1, 2019
• Est. completion date: March 31, 2027

Study information

• Verified date: July 2023
• Source: VA Office of Research and Development
• Contact: Brenna M Lobb, BA MA MPH
• Phone: (503) 220-8262
• Email: Brenna.Lobb[@]va.gov
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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 information / eligibility

• Status: Recruiting
• Enrollment: 120
• Est. completion date: March 31, 2027
• Est. primary completion date: July 1, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 50 Years and older

Eligibility

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)

Related Conditions & MeSH terms

• Dyskinesia, Drug-Induced
• Dyskinesias
• Parkinson Disease

Intervention

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

Locations

Country	Name	City	State
United States	Oregon Health & Science University	Portland	Oregon
United States	VA Portland Health Care System, Portland, OR	Portland	Oregon
United States	VA Puget Sound Health Care System Seattle Division, Seattle, WA	Seattle	Washington

Sponsors (2)

Lead Sponsor	Collaborator
VA Office of Research and Development	Oregon Health and Science University

Country where clinical trial is conducted

United States, 

References & Publications (3)

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. — View Citation

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. — View Citation

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	phosphorylated ERK1/2 Levels in CD3/CD20 lymphocytes	Immunodetection of pERK with antibody against the phosphorylated forms of Tyrosine202 and 204 of ERK1/2 (AlexaFluor488 BD Biosciences) will occur in lymphocytes isolated from whole blood using flow cytometry.	11:15 am