Reducing Dyskinesia in Parkinson's Disease With Omega-3 Fatty Acids (RLID-PD)

• ClinicalTrials.gov Identifier: NCT01563913
• Recruitment Status: Completed
• First Posted: March 27, 2012
• Results First Posted: May 29, 2018
• Last Update Posted: June 29, 2018
• Sponsor: VA Office of Research and Development
• Collaborator: Oregon Health and Science University
• Information provided by (Responsible Party): VA Office of Research and Development

Study Description

Brief Summary:

The purpose of this research study is to measure the safety (side effects) of an Omega 3 Fatty acid called docosahexanoic acid (DHA) and measure the dyskinesia (involuntary movements) in Parkinson 's disease (PD).

Condition or disease	Intervention/treatment	Phase
Parkinson's Disease	Drug: Docosahexaenoic Acid (DHA); Drug: Placebo	Phase 1

Detailed Description:

Levodopa induced dyskinesias (LID) are involuntary, abnormal movements that occur in most patients with Parkinson disease(PD) as a consequence of chronic use of the most effective symptomatic drug, levodopa (LD). LID can range from subtle and unobtrusive to marked and disabling. There are surprisingly few treatments for LID, including amantadine and deep brain stimulation. In many instances, amantadine is either poorly tolerated, or provides inadequate benefit, and only a small minority are appropriate candidates for surgery. Given the finding that docosahexanoic acid (the most abundant omega-3 fatty acid in the brain), delays the onset and reduces the severity of dyskinesia in two different animal models of LID, a trial of docosahexanoic acid (DHA) in PD subjects about to start LD as part of their drug regimen, to prevent or slow the progression of LID is warranted.

Prior to embarking on a large trial, preliminary data about safety and tolerability of DHA in PD subjects is needed, and collection of this data is the primary outcome of this pilot project proposal. 40 subjects who have not yet used levodopa, but are about to begin it will be randomized to daily DHA or placebo. Safety laboratory testing, adverse event monitoring, DHA plasma and CSF levels as well as compliance/subject retention will be outcomes collected.

In addition, preliminary data about modification of incidence rates will be collected and compared between the two treatment groups. This information will aid in calculating an appropriate sample size and treatment period for a larger definitive future study.

Dyskinesia manifests overwhelmingly when plasma levodopa levels are high enough to cause anti-parkinsonian benefits, and lessens or stops when levodopa levels drop below a threshold. Thus, the subject's dyskinesia measurements must occur during a levodopa administration period. Dyskinesia measurement will occur during a two-hour levodopa cycle administered to subjects at weeks 0, 6, 24, 52, 76. It is expected that a good proportion of subjects will manifest dyskinesia within the two-year observation period, as previous studies using the most objective means to measure dyskinesia report incidence rates of 67% or greater within the first year of levodopa use. An instrument to measure dyskinesia developed by this center will be used as an additional outcome, and is expected to measure dyskinesia more accurately and with greater sensitivity than the gold standard methods of clinical rating scales.

By conclusion of this pilot project, the safety and tolerability, subject retention and compliance, plasma/CSF levels of DHA administration will be determined. Trends in dyskinesia development may be measured. This will provide the needed background information to proceed with a future larger trial of DHA to prevent dyskinesia in PD.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 33 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Investigator, Outcomes Assessor)
• Primary Purpose: Other
• Official Title: Reducing Dyskinesia in Parkinson Disease With Omega-3 Fatty Acids
• Study Start Date: October 2012
• Actual Primary Completion Date: June 2016
• Actual Study Completion Date: June 2016

Arms and Interventions

Arm	Intervention/treatment
Experimental: Arm 1; Docosahexaenoic Acid (DHA)	Drug: Docosahexaenoic Acid (DHA); Docosahexaenoic Acid (DHA) 2 grams per day taken for 1.5 years; Other Name: DHA
Placebo Comparator: Arm 2; Placebo	Drug: Placebo; Sugar Pill, taken for 1.5 years; Other Name: Sugar Pill

Outcome Measures

Primary Outcome Measures :

1. Efficacy of DHA - Change in Blood ng/dL Levels [ Time Frame: baseline and 1.5 years ]
   Therapeutic level monitoring will be accomplished by analyzing blood levels for DHA.
2. Efficacy of DHA - Number of Participants With An Abnormal Safety Lab (CBC) [ Time Frame: Year 1 ]
   This study is seeking to determine the safety/efficacy of DHA in Parkinson's disease patients. The safety/efficacy of DHA will be determined using periodic safety lab information. Safety labs for complete blood count (CBC) were performed at each inpatient visit, reviewed by the PI, and marked as normal or abnormal.

Secondary Outcome Measures :

1. Forceplate Measured Dyskinesia [ Time Frame: baseline and 1.5 years ]
   Dyskinesia are abnormal movements caused by levodopa. These abnormal movements will be measured with a forceplate (a device that is similar to a door mat). Dyskinesia will be examined at all inpatient visits and area under the curves will be compared with a clinical rating scale to measure the development of dyskinesia after starting levodopa therapy.

Eligibility Criteria

• Ages Eligible for Study: 21 Years to 99 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• Diagnosed with Parkinsons disease
• No levodopa (Sinemet) treatment or prior exposure to levodopa

Exclusion Criteria:

• Prior exposure to levodopa
• Unable to stand for 1 minute without aid
• Sensory deficits on feet
• Significant cognitive impairment
• Current use of dopamine receptor blocking medications (depakote, lithium, amiodarone, tetrabenazine, metoclopramide, dronabinol)
• Current fish oil or lutein supplementation
• Allergy to soy

Contacts and Locations

Locations

United States, Oregon

VA Portland Health Care System, Portland, OR

Portland, Oregon, United States, 97239

Sponsors and Collaborators

VA Office of Research and Development

Oregon Health and Science University

Investigators

• Principal Investigator: Kathryn Anne Chung, MD; VA Portland Health Care System, Portland, OR

More Information

Publications of Results:

Péchevis M, Clarke CE, Vieregge P, Khoshnood B, Deschaseaux-Voinet C, Berdeaux G, Ziegler M; Trial Study Group. Effects of dyskinesias in Parkinson's disease on quality of life and health-related costs: a prospective European study. Eur J Neurol. 2005 Dec;12(12):956-63.

Rascol O, Brooks DJ, Korczyn AD, De Deyn PP, Clarke CE, Lang AE. A five-year study of the incidence of dyskinesia in patients with early Parkinson's disease who were treated with ropinirole or levodopa. N Engl J Med. 2000 May 18;342(20):1484-91.

Nutt JG, Carter JH, Lea ES, Sexton GJ. Evolution of the response to levodopa during the first 4 years of therapy. Ann Neurol. 2002 Jun;51(6):686-93.

Chung KA, Lobb BM, Nutt JG, McNames J, Horak F. Objective measurement of dyskinesia in Parkinson's disease using a force plate. Mov Disord. 2010 Apr 15;25(5):602-8. doi: 10.1002/mds.22856.

Other Publications:

Salem N Jr, Litman B, Kim HY, Gawrisch K. Mechanisms of action of docosahexaenoic acid in the nervous system. Lipids. 2001 Sep;36(9):945-59. Review.

• Responsible Party: VA Office of Research and Development
• ClinicalTrials.gov Identifier: NCT01563913
• Other Study ID Numbers: CLIN-006-11S; 2907 ( Other Identifier: Portland VA Medical Center ); 8012 ( Other Identifier: Oregon Health & Science University )
• First Posted: March 27, 2012
• Results First Posted: May 29, 2018
• Last Update Posted: June 29, 2018
• Last Verified: May 2018

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

Keywords provided by VA Office of Research and Development:

Parkinsons disease; supplement; DHA; dyskinesia; abnormal movements

Additional relevant MeSH terms:

Parkinson Disease; Dyskinesias; Parkinsonian Disorders; Basal Ganglia Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Movement Disorders; Neurodegenerative Diseases; Neurologic Manifestations