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Trial registered on ANZCTR


Trial ID
ACTRN12614001019695
Ethics application status
Approved
Date submitted
15/09/2014
Date registered
22/09/2014
Date last updated
25/10/2016
Type of registration
Prospectively registered

Titles & IDs
Public title
Omega-3 supplements for treating dry eye disease
Scientific title
A proof-of-concept, placebo-controlled clinical trial to compare the efficacy of different forms of omega-3 essential fatty acid supplements for treating mild-to-moderate dry eye disease
Secondary ID [1] 285339 0
None
Universal Trial Number (UTN)
U1111-1161-6894
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Dry eye disease 293065 0
Condition category
Condition code
Eye 293340 293340 0 0
Diseases / disorders of the eye

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Arm 1 (Treatment 1): triglyceride form omega-3 oral supplement (1000mg EPA + 500mg DHA per day) for three months.
Arm 2 (Treatment 2): phospholipid form omega-3 oral supplement (945mg EPA + 510mg DHA per day) for three months.
Adherence to treatment will be monitored by assessing the return of unused capsules at monthly visits.
Intervention code [1] 290256 0
Treatment: Other
Comparator / control treatment
Arm 3 (Placebo): olive oil oral supplement (1500mg per day) for three months
Control group
Placebo

Outcomes
Primary outcome [1] 293170 0
Patient symptoms: ocular surface disease index (OSDI) survey score, a quantitative and validated survey instrument to grade the severity of dry eye disease.
Timepoint [1] 293170 0
Change in OSDI score between Days 1 and 90.
Primary outcome [2] 293171 0
Tear osmolarity: electrolyte concentration of the tears (measured in mOsm/L using the TearLab system (TearLab Corporation Pty Ltd), which is currently considered a gold standard for dry eye assessment).
Timepoint [2] 293171 0
Change in tear osmolarity between Days 1 and 90.
Secondary outcome [1] 310487 0
Patient symptoms: OSDI survey score (as described for primary outcome 1).
Timepoint [1] 310487 0
Change from Day 1 at Days 30 +/- 7, 60 +/- 7
Secondary outcome [2] 310488 0
Tear osmolarity: electrolyte concentration of the tears (measured in mOsm/L using the TearLab system (TearLab Corporation Pty Ltd).
Timepoint [2] 310488 0
Change from Day 1 at Days 30 +/- 7, 60 +/- 7.
Secondary outcome [3] 310489 0
Tear inflammatory cytokines: concentration of cytokines (pg/ml) from basal tear samples (measured using a human multiple-CBA kit for IL-2, IL-6, IL-10, Il-17A, TNF-alpha, IFN-gamma).
Timepoint [3] 310489 0
Change from Day 1 at Days 30 +/- 7, 60 +/- 7, 90 +/- 7.
Secondary outcome [4] 310490 0
Non-invasive tear break-up time (NITBUT): measure of tear film stability, quantified using the NKBUT (Oculus Keratograph K5) and TFSQ (Medmont E300 topographer) analysis tools.
Timepoint [4] 310490 0
Change from Day 1 to Days 30 +/- 7, 60 +/- 7, 90 +/- 7.
Secondary outcome [5] 310491 0
Tear meniscus height (TMH): measure of tear volume, quantified using the Oculus Keratograph K5 and anterior optical coherence tomography (OCT) (Topcon OCT).
Timepoint [5] 310491 0
Change from Day 1 to Days 30 +/- 7, 60 +/- 7, 90 +/- 7.
Secondary outcome [6] 310492 0
Conjunctival and limbal redness: standard clinical assessment for anterior eye inflammation, quantified with the R-scan feature of the Oculus Keratograph K5.
Timepoint [6] 310492 0
Change from Day 1 to Days 30 +/- 7, 60 +/- 7, 90 +/- 7.
Secondary outcome [7] 310493 0
Central corneal haze: corneal reflectivity quantified in the central cornea using transverse images captured with the Topcon OCT.
Timepoint [7] 310493 0
Change from Day 1 to Days 30 +/- 7, 60 +/- 7, 90 +/- 7.
Secondary outcome [8] 310494 0
Tear stability: standard clinical measure of TBUT using sodium fluorescein dye.
Timepoint [8] 310494 0
Change from Day 1 to Days 30 +/- 7, 60 +/- 7, 90 +/- 7
Secondary outcome [9] 310495 0
Grading of the extent and confluence of sodium fluorescein staining of the cornea and conjunctiva using the standardised Oxford grading system.
Timepoint [9] 310495 0
Change from Day 1 to Days 30 +/- 7, 60 +/- 7, 90 +/- 7.
Secondary outcome [10] 310496 0
Grading of the extent and confluence of lissamine green staining of the cornea and conjunctiva using the standardised Oxford grading system.
Timepoint [10] 310496 0
Change from Day 1 to Days 30 +/- 7, 60 +/- 7, 90 +/- 7
Secondary outcome [11] 310497 0
tear production: non-stimulated tear production (measured using Schirmer strips with topical anaesthetic).
Timepoint [11] 310497 0
Change from Day 1 to Days 30 +/- 7, 60 +/- 7, 90 +/- 7.
Secondary outcome [12] 310498 0
Meibomian gland (MG) integrity: assessed using quantitative infra-red meibography of the superior and inferior eyelids (Oculus Keratograph K5) for the extent of MG drop-out.
Timepoint [12] 310498 0
Change from Day 1 to Days 30 +/- 7, 60 +/- 7, 90 +/- 7.

Eligibility
Key inclusion criteria
Mild-to-moderate dry eye symptoms (OSDI score: 18-65) and tear osmolarity of at least 316mOsm/L in at least one eye
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Co-morbid ocular pathology (e.g., ocular infection, intra-ocular inflammation)
Uncontrolled systemic disease
Known or suspected allergy to fish/seafood, nuts, oil or gelatin
Current medication with oral omega-3 supplements
Contact lens wear within one month prior to Day 1 or intended wear of contact lenses over the course of the study
A systemic medical condition where omega-3 supplements are contraindicated (e.g., bleeding disorders, diabetes, atrial fibrillation, familial immunocompromise, adenomatous polyposis, liver disease.)

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Subject must satisfy all eligibility criteria and provide written informed consent to participate.
Eligible subjects will be enrolled and assigned in sequential order to one of the three treatment groups (olive oil, triglyceride omega-3 or phospholipid omega-3) using a participant/randomisation number sequence generated in advance that randomly assigns subjects to one of the three groups. This randomisation schedule will be generated by an independent data manager and provided to a separate independent entity responsible for labelling the investigational product.
To preserve masking, the three different types of oral supplements will be packaged in identical containers. Investigators collecting and analysing data will not be involved in the reconciliation of returned study product.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
An independent data manager will generate a simple random number sequence in Microsoft Excel for participant randomisation. The sequence will include equal numbers for the three treatment groups. The code will be kept by the independent data manager and made available for labelling of the investigational product by sequential participant number.
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint(s)
Efficacy
Statistical methods / analysis
To detect a 20% difference in outcome measures treatment and control groups, for 90% power at a confidence level of 95%, the sample size was calculated as 16 participants per group. A total 20 participants will be recruited to compensate for any drop-outs.
Repeated measures analyses of variance (RM-ANOVA) will be performed to assess for treatment effects over time.

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment postcode(s) [1] 9086 0
3053 - Carlton

Funding & Sponsors
Funding source category [1] 289954 0
University
Name [1] 289954 0
University of Melbourne early career researcher grant (ECRG) awarded to CI: Dr Laura Downie (2014)
Address [1] 289954 0
The University of Melbourne
Parkville
Victoria, Australia 3010
Country [1] 289954 0
Australia
Primary sponsor type
University
Name
The University of Melbourne
Address
The University of Melbourne
Parkville
Victoria, Australia 3010
Country
Australia
Secondary sponsor category [1] 288644 0
None
Name [1] 288644 0
Address [1] 288644 0
Country [1] 288644 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 291671 0
University of Melbourne Human Research Ethics Committee – Health Sciences sub-committee
Ethics committee address [1] 291671 0
Office for Research Ethics and Integrity
The University of Melbourne
Level 1, 780 Elizabeth Street,
Parkville, Victoria Australia 3010
Ethics committee country [1] 291671 0
Australia
Date submitted for ethics approval [1] 291671 0
Approval date [1] 291671 0
04/02/2014
Ethics approval number [1] 291671 0
1341262

Summary
Brief summary
Dry eye disease is a common condition, affecting up to 30% of adults. Common symptoms of dry eye disease include eye irritation (e.g., burning, grittiness, scratchiness, wateriness) and/or fluctuations in vision. Currently, the main form of treatment for dry eye disease is the use of artificial tears (lubrication drops), which can assist in reducing these symptoms by supplementing the deficient tear fluid. However, as artificial tears fail to address the underlying cause of dry eye disease, for many patients they are inadequate in completely relieving symptoms. New and enhanced therapeutic treatments are therefore needed.

Inflammation plays an important role in the development of dry eye disease. There is growing scientific evidence that dietary supplementation with omega-3 essential fatty acids, may be of benefit in reducing inflammation throughout the body, including in the eye. A well recognised source of omega-3s is fish oil, which has undergone some preliminary investigations in relation to treating dry eye disease, however further research is needed to substantiate these findings.

The aim of this ‘proof-of-concept’, single site clinical trial is to evaluate the benefit of phospholipid form omega-3 supplements for the treatment of dry eye disease, and whether this form of omega-3 provides any benefit over triglyceride omega-3s. The effects of both forms of omega-3 supplements will be compared with a control group, who will consume an olive oil supplement.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 51450 0
Dr Laura Downie
Address 51450 0
Lecturer and Clinical Leader
Department of Optometry and Vision Sciences
Level 4 – Alice Hoy Building (Bldg 162), Monash Road
The University of Melbourne
Parkville, Victoria, Australia 3010.
Country 51450 0
Australia
Phone 51450 0
+613 9035 3043
Fax 51450 0
+613 9035 9905
Email 51450 0
ldownie@unimelb.edu.au
Contact person for public queries
Name 51451 0
Dr Laura Downie
Address 51451 0
Lecturer and Clinical Leader
Department of Optometry and Vision Sciences
Level 4 – Alice Hoy Building (Bldg 162), Monash Road
The University of Melbourne
Parkville, Victoria, Australia 3010.
Country 51451 0
Australia
Phone 51451 0
+613 9035 3043
Fax 51451 0
Email 51451 0
ldownie@unimelb.edu.au
Contact person for scientific queries
Name 51452 0
Dr Laura Downie
Address 51452 0
Lecturer and Clinical Leader
Department of Optometry and Vision Sciences
Level 4 – Alice Hoy Building (Bldg 162), Monash Road
The University of Melbourne
Parkville, Victoria, Australia 3010.
Country 51452 0
Australia
Phone 51452 0
+613 9035 3043
Fax 51452 0
Email 51452 0
ldownie@unimelb.edu.au