Transcript Dry Eye Assessment and Management Study

The DRy Eye Assessment and Management
(DREAM) Study
NCT02128763
Penny Asbell1, Maureen Maguire2, Ellen Peskin1, Neha Gadaria1, Kathy McWilliams2, Nataliya Antonova1, Rubinee
Simmasalam1, Brendan Barry1 for the DREAM Research Group
1Department of Ophthalmology Mount Sinai Hospital, New York, NY, 2 University of Pennsylvania, Philadelphia, PA.
Introduction
Dry Eye Disease (DED) is characterized by ocular surface changes and tear film instability. The chief complaints of patients are chronic pain or irritation and associated
visual disturbance. Inflammation is considered a core mechanism in the pathogenesis of DED, although the pathogenesis of DED is likely multifactorial,. Inflammation in
turn leads to ocular surface damage and further exacerbation of DED, thus creating a self-perpetuating vicious cycle of chronic DED.1,2,3,4,5,6,7,8 Clinical evidence indicates
that anti-inflammatory therapies may be able to break this cycle of DED and inflammation.
Rationale for DREAM STUDY:
Though there has been some success with use of anti-inflammatory treatments for DED, most of the current options are limited by risks or side-effects, leaving many DED
patients with continued signs and symptoms. An anti-inflammatory nutritional supplement such as Omega-3 fatty acids is an appealing alternative for many
patients. While RCT studies support the use of Omega-3 for other inflammatory diseases, such as rheumatoid arthritis and asthma, the data on its use in DED is limited
and with varying outcomes and success rates . Most studies concerning Omega-3 and DED are small with data recorded from a single site, with different outcome
measures and using varying combinations of Omega-3 and other fatty acids with short study duration and contrasting results.9 The NIH has called for increased evidence
on efficacy and safety of supplements for chronic disease, including randomized clinical trials. The U.S. Department of Health & Human services has also noted that few
trials have established the efficacy of supplements in chronic disease (http://www.ahrq.gov/clinic/tp/multivittp.htm).
The DREAM study will be the first large scale, multicenter, double masked randomized controlled trial(RCT) using Omega-3 for DED. Work done in our NEI planning
grant, which included a small scale clinical trial with Omega-3 supplements (DREAM: Feasibility study), extensive review of current literature and collaboration with experts
in various fields, helped us identify criteria for the DREAM protocol , including standardized outcome measures, biomarkers of inflammation, and compliance measures
(blood tests). The DREAM study design of a twelve-month primary RCT trial followed by a twelve-month extension study, enables us to have a longitudinal assessment of
DED on a cohort of well characterized subjects . The results obtained from DREAM will help us better understand and describe DED itself and specifically determine the
efficacy and safety of the use of Omega-3 in treatment of DED.
Objective
1- To test the effectiveness of Omega-3 supplementation for Dry Eye Disease (DED) in a Primary Clinical Trial.
2- To better understand DED features by observation of a well-characterized group of patients treated with either Omega-3 or placebo over twelve months.
3- To determine the effects of extended use and discontinuation of Omega-3 through an Extension Trial.
Methods
Primary Trial: multi-center, double-masked, placebo-controlled, prospective
randomized clinical trial with 600 patients at 20 sites. Active oral supplement
(Omega-3) or placebo will be taken for a year.
Extension Trial: Randomized Withdrawal trial will evaluate whether Omega-3
taken over another year will have an additional effect or if one year is enough to
break up the chain of inflammation in DED. Subjects recruited from patients on
active supplements in the Primary Trial.
Dose: 2000 mg EPA and 1000 mg DHA per day
Outcome Measures:
Primary: Change in OSDI score
Secondary:
• Compliance with the study
treatment protocol as
measured by changes in
blood
levels of essential fatty
acids and pill counts.
• Incidence of adverse
events
• Change in Signs of DED
(conjunctival and corneal
. staining, TBUT, Shirmer’s test)
Exploratory:
• Frequency of
Signs measured by
administration of artificial tearskeratography: TBUT, TMH,
and other dry eye treatments redness, meibography
• Contrast sensitivity
Meibomian gland secretion
• Quality of life as measured evaluation
by the SF-36
Tear osmolarity
• Change in Brief Ocular
Biomarker levels: MMP-9, tear
Discomfort Index (BODI)
cytokine levels, HLA-DR
score.
expression.
• Cost-effectiveness of using
Omega-3
Inclusion Criteria:
•
Greater than or equal to 2 of the following 4 signs in the same eye repeated at 2 visits:
Conjunctival staining present and greater than or equal to 1 (out of possible score of 6 per eye)
Corneal fluorescein staining present and greater than or equal to 4 (out of a possible score of 15 per eye)
Tear film break-up time (TBUT) less than or equal to 7 seconds
Schirmer's test greater than or equal to 1 and less than or equal to 7 mm in 5 minutes.
•
OSDI score: 25-80 at screening, 21-80 at baseline.
• Symptoms of DED for greater than or equal to 6 months.
•
Use of or desire to use artificial tears at least 2 times per day in preceding 2 weeks
• Ability to swallow large, soft gelcaps
Exclusion Criteria:
• Allergic to ingredients in supplements or placebo
•
Wears contact lenses
•
Pregnant, nursing, or lactating
•
Current ocular infection, inflammation, or acute allergic conjunctivitis
•
History of: ocular herpetic keratitis, ocular surgery in past 6 months, LASIK surgery, use of glaucoma medicine or surgery for glaucoma, liver disease,
atrial fibrillation, hemophilia or bleeding tendencies
•
In the process of any anticoagulation therapy
•
Eyelid abnormalities or extensive ocular scarring
•
Use of EPA/DHA supplements in excess of 1200 mg per day
•
Current use, insufficient washout period, or intent to change specific treatments for dry eye disease
Results
This is the first NEI-funded randomized placebo controlled clinical trial on DED. Results will answer the question of the efficacy and safety of use of
Omega-3 in treating dry eye disease. The primary outcomes, secondary outcomes and exploratory outcomes- including biomarkers of inflammation of the
ocular surface will provide a expanded “face “ for dry eye disease. Studying a well-characterized cohort will improve our ability to diagnose and treat
patients with dry eye disease and may provide new targets for treatment. Results are expected in 2015-2016.
Conclusions
DED is a multifactorial disease and the DREAM study will provide significant insights in understanding the role of Omega-3 in treating dry eye, as well as,
the impact of DED on quality of life. Furthermore, studying biomarkers may shed new light on the mechanisms of action that lead to DED.
Supported Grants: NEI U10EY022881 & U10EY022879
Financial Disclosure: Active and placebo supplements have been donated by the Access Business Group with fish oil oil donated by EPAX Norway AS.
Commercial Relations: None
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Contact e-mail: [email protected]