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

• Sponsor: VA Office of Research and Development (U.S. Fed)
• Overall Status: Completed
• CT.gov ID: NCT01563913
• Collaborator: Oregon Health and Science University (Other)
• Enrollment: 33
• Location: 1
• Arms: 2
• Duration (Months): 44
• Patients Per Site Per Month: 0.8

Study Details

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
• 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: Oct 1, 2012
• Actual Primary Completion Date: Jun 1, 2016
• Actual Study Completion Date: Jun 1, 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 Names: DHA
Placebo Comparator: Arm 2 Placebo	Drug: Placebo; Sugar Pill, taken for 1.5 years; Other Names: Sugar Pill

Outcome Measures

Primary Outcome Measures

1. Efficacy of DHA - Change in Blood ng/dL Levels [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) [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 [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

Criteria

• Ages Eligible for Study: 21 Years to 99 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

	Site	City	State	Country	Postal Code
1	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

Study Documents (Full-Text)

None provided.

More Information

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; 8012
• First Posted: Mar 27, 2012
• Last Update Posted: Jun 29, 2018
• Last Verified: May 1, 2018

• Individual Participant Data (IPD) Sharing Statement: No
• 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

Study Results

Participant Flow

Recruitment Details	Subjects were recruited from two large urban hospitals with Movement disorder specialty clinics in the NW USA over a 30 month (2.5 year) recruitment period. 34 subjects were screened. 1 subject screen failed due to prior exposure to levodopa. 33 subjects were randomized to DHA or placebo arms. 30 subjects returned and completed visit 1.

Arm/Group Title	Docosahexaenoic Acid (DHA)	Placebo
Arm/Group Description	Docosahexaenoic Acid (DHA) 2 grams per day taken for 1.5 years	Placebo: Sugar Pill, taken for 1.5 years
Period Title: Overall Study
STARTED	15	15
COMPLETED	13	15
NOT COMPLETED	2	0

Baseline Characteristics

Arm/Group Title	Docosahexaenoic Acid	Placebo:	Total
Arm/Group Description	Docosahexaenoic Acid (DHA) 2 grams per day taken for 1.5 years	Placebo: Sugar Pill, taken for 1.5 years	Total of all reporting groups
Overall Participants	15	15	30
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	68.3 (7.6)	67.0 (8.5)	68.0 (7.6)
Sex: Female, Male (Count of Participants)
Female	1 6.7%	2 13.3%	3 10%
Male	14 93.3%	13 86.7%	27 90%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%	0 0%	0 0%
Not Hispanic or Latino	15 100%	15 100%	30 100%
Unknown or Not Reported	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	0 0%	0 0%	0 0%
White	15 100%	15 100%	30 100%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%
Region of Enrollment (Count of Participants)
United States	15 100%	15 100%	30 100%
PD Symptom Duration (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	3.2 (1.9)	4.6 (3.8)	3.8 (2.9)
Education (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	16.0 (3.2)	15.7 (3.1)	15.9 (3.2)
DHA Intake at Screening (mg/day) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [mg/day]	119.9 (77.4)	148.7 (88.1)	134.8 (82.9)
MoCA Score (units on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [units on a scale]	25.1 (3.8)	24.7 (2.6)	24.9 (3.2)
Unified Parkinsons Disease Rating Scale (UPDRS-III) (units on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [units on a scale]	34.6 (9.7)	29.2 (10.9)	31.9 (10.5)
Hoehn & Yahr (units on a scale) [Median (Full Range) ]
Median (Full Range) [units on a scale]	2.5	2.0	2.25
Levodopa Initial Dose (mg/day) [Median (Full Range) ]
Median (Full Range) [mg/day]	300.0	300.0	300.0
Levodopa Exposure (Equivalence) (mg/day) [Median (Full Range) ]
Median (Full Range) [mg/day]	540.0	187.5	345.0

Outcome Measures

1. Primary Outcome

Title	Efficacy of DHA - Change in Blood ng/dL Levels
Description	Therapeutic level monitoring will be accomplished by analyzing blood levels for DHA.
Time Frame	baseline and 1.5 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Docosahexaenoic Acid	Placebo:
Arm/Group Description	Docosahexaenoic Acid (DHA) 2 grams per day taken for 1.5 years	Placebo: Sugar Pill, taken for 1.5 years
Measure Participants	13	15
Mean (Standard Deviation) [ng/dL - Blood]	102.18 (50.0)	-13.20 (33.12)

2. Primary Outcome

Title	Efficacy of DHA - Number of Participants With An Abnormal Safety Lab (CBC)
Description	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.
Time Frame	Year 1

Outcome Measure Data

Analysis Population Description

3 participants did not complete year 1 visit (2 withdrew prior to year 1, 1 refused to travel for visit), 2 blood samples were hemolyzed and could not be analyzed.

Arm/Group Title	Docosahexaenoic Acid	Placebo:
Arm/Group Description	Docosahexaenoic Acid (DHA) 2 grams per day taken for 1.5 years	Placebo: Sugar Pill, taken for 1.5 years
Measure Participants	11	14
Count of Participants [Participants]	0 0%	0 0%

3. Secondary Outcome

Title	Forceplate Measured Dyskinesia
Description	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.
Time Frame	baseline and 1.5 years

Outcome Measure Data

Analysis Population Description

Docosahexaenoic Acid Arm: 2 participants withdrew after the 6 week visit, 4 didn't complete visit 5 due to: wife's death, too busy, new diagnosis of cancer.

Arm/Group Title	Docosahexaenoic Acid	Placebo:
Arm/Group Description	Docosahexaenoic Acid (DHA) 2 grams per day taken for 1.5 years	Placebo: Sugar Pill, taken for 1.5 years
Measure Participants	9	15
Dyskinesia Present	3 20%	6 40%
Dyskinesia Absent	6 40%	9 60%

Adverse Events

Time Frame	Adverse Event data were collected over 1.5 years. Regular monthly phone calls were placed to participants to ask about adverse events, hospitalizations, and changes in medications. Adverse events were also gathered at the in-person visit occurring at 0 weeks, 6 weeks, 24 weeks, 52 weeks, and 72 weeks.
Arm/Group Title	Docosahexaenoic Acid		Placebo:
Arm/Group Description	Docosahexaenoic Acid (DHA) 2 grams per day taken for 1.5 years		Placebo: Sugar Pill, taken for 1.5 years
All Cause Mortality
	Docosahexaenoic Acid		Placebo:
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/15 (0%)		0/15 (0%)
Serious Adverse Events
	Docosahexaenoic Acid		Placebo:
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/15 (0%)		2/15 (13.3%)
Nervous system disorders
Syncope	0/15 (0%)	0	1/15 (6.7%)	1
Reproductive system and breast disorders
Prostate Cancer	0/15 (0%)	0	1/15 (6.7%)	1
Other (Not Including Serious) Adverse Events
	Docosahexaenoic Acid		Placebo:
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	6/15 (40%)		4/15 (26.7%)
Cardiac disorders
Atrial Fibrillation	1/15 (6.7%)	1	2/15 (13.3%)	2
Gastrointestinal disorders
Nausea	5/15 (33.3%)	5	2/15 (13.3%)	2
Vomiting	1/15 (6.7%)	1	2/15 (13.3%)	2
Infections and infestations
Urinary Track Infection	0/15 (0%)	0	2/15 (13.3%)	3
Nervous system disorders
Dizziness	1/15 (6.7%)	2	0/15 (0%)	0
Reproductive system and breast disorders
Gynecomastia	2/15 (13.3%)	2	0/15 (0%)	0

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.