Clinical trial NCT01563913: Reducing Dyskinesia in Parkinson's Disease With Omega-3 Fatty Acids
Official title: Reducing Dyskinesia in Parkinson Disease With Omega-3 Fatty Acids
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Parkinson's Disease
Keywords: Parkinsons disease
supplement
DHA
dyskinesia
abnormal movements
Lead sponsor: VA Office of Research and Development
Sponsor class: FED
Collaborators: name: Oregon Health and Science University
First posted: 2012-03-27
Enrollment: 33
Sex: ALL
Minimum age (years): 21
Maximum age (years): 99
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: OTHER

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).

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.

Eligibility 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

Primary outcomes:
measure: Efficacy of DHA - Change in Blood ng/dL Levels
timeFrame: baseline and 1.5 years
measure: Efficacy of DHA - Number of Participants With An Abnormal Safety Lab (CBC)
timeFrame: Year 1
Secondary outcomes:
measure: Forceplate Measured Dyskinesia
timeFrame: baseline and 1.5 years
Other outcomes:
Locations:
city: Portland
country: United States
facility: VA Portland Health Care System, Portland, OR
state: Oregon
Study officials:
affiliation: VA Portland Health Care System, Portland, OR
name: Kathryn Anne Chung, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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. doi: 10.1007/s11745-001-0805-6.
citation: Pechevis 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. doi: 10.1111/j.1468-1331.2005.01096.x.
citation: 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. doi: 10.1056/NEJM200005183422004.
citation: 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. doi: 10.1002/ana.10189.
citation: 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.