ANZCTR - Registration

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Trial registered on ANZCTR

Registration number

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]

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

Condition category

Condition code

Eye

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]

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]

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]

Change in OSDI score between Days 1 and 90.

Primary outcome [2]

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]

Change in tear osmolarity between Days 1 and 90.

Secondary outcome [1]

Patient symptoms: OSDI survey score (as described for primary outcome 1).

Timepoint [1]

Change from Day 1 at Days 30 +/- 7, 60 +/- 7

Secondary outcome [2]

Tear osmolarity: electrolyte concentration of the tears (measured in mOsm/L using the TearLab system (TearLab Corporation Pty Ltd).

Timepoint [2]

Change from Day 1 at Days 30 +/- 7, 60 +/- 7.

Secondary outcome [3]

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]

Change from Day 1 at Days 30 +/- 7, 60 +/- 7, 90 +/- 7.

Secondary outcome [4]

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]

Change from Day 1 to Days 30 +/- 7, 60 +/- 7, 90 +/- 7.

Secondary outcome [5]

Tear meniscus height (TMH): measure of tear volume, quantified using the Oculus Keratograph K5 and anterior optical coherence tomography (OCT) (Topcon OCT).

Timepoint [5]

Change from Day 1 to Days 30 +/- 7, 60 +/- 7, 90 +/- 7.

Secondary outcome [6]

Conjunctival and limbal redness: standard clinical assessment for anterior eye inflammation, quantified with the R-scan feature of the Oculus Keratograph K5.

Timepoint [6]

Change from Day 1 to Days 30 +/- 7, 60 +/- 7, 90 +/- 7.

Secondary outcome [7]

Central corneal haze: corneal reflectivity quantified in the central cornea using transverse images captured with the Topcon OCT.

Timepoint [7]

Change from Day 1 to Days 30 +/- 7, 60 +/- 7, 90 +/- 7.

Secondary outcome [8]

Tear stability: standard clinical measure of TBUT using sodium fluorescein dye.

Timepoint [8]

Change from Day 1 to Days 30 +/- 7, 60 +/- 7, 90 +/- 7

Secondary outcome [9]

Grading of the extent and confluence of sodium fluorescein staining of the cornea and conjunctiva using the standardised Oxford grading system.

Timepoint [9]

Change from Day 1 to Days 30 +/- 7, 60 +/- 7, 90 +/- 7.

Secondary outcome [10]

Grading of the extent and confluence of lissamine green staining of the cornea and conjunctiva using the standardised Oxford grading system.

Timepoint [10]

Change from Day 1 to Days 30 +/- 7, 60 +/- 7, 90 +/- 7

Secondary outcome [11]

tear production: non-stimulated tear production (measured using Schirmer strips with topical anaesthetic).

Timepoint [11]

Change from Day 1 to Days 30 +/- 7, 60 +/- 7, 90 +/- 7.

Secondary outcome [12]

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]

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

Sex

Both males and females

Can healthy volunteers participate?

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

6/10/2014

Actual

5/11/2014

Date of last participant enrolment

Anticipated

Actual

18/08/2015

Date of last data collection

Anticipated

Actual

24/11/2015

Sample size

Target

Accrual to date

Final

Recruitment in Australia

Recruitment state(s)

VIC

Recruitment postcode(s) [1]

3053 - Carlton

Funding & Sponsors

Funding source category [1]

University

Name [1]

University of Melbourne early career researcher grant (ECRG) awarded to CI: Dr Laura Downie (2014)

Address [1]

The University of Melbourne
Parkville
Victoria, Australia 3010

Country [1]

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]

None

Name [1]

Address [1]

Country [1]

Ethics approval

Ethics application status

Approved

Ethics committee name [1]

University of Melbourne Human Research Ethics Committee – Health Sciences sub-committee

Ethics committee address [1]

Office for Research Ethics and Integrity
The University of Melbourne
Level 1, 780 Elizabeth Street,
Parkville, Victoria Australia 3010

Ethics committee country [1]

Australia

Date submitted for ethics approval [1]

Approval date [1]

04/02/2014

Ethics approval number [1]

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

Dr Laura Downie

Address

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

Australia

Phone

+613 9035 3043

Fax

+613 9035 9905

ldownie@unimelb.edu.au

Contact person for public queries

Name

Laura Downie

Address

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

Australia

Phone

+613 9035 3043

Fax

ldownie@unimelb.edu.au

Contact person for scientific queries

Name

Laura Downie

Address

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

Australia

Phone

+613 9035 3043

Fax

ldownie@unimelb.edu.au

No information has been provided regarding IPD availability

What supporting documents are/will be available?

No Supporting Document Provided

Results publications and other study-related documents

Documents added manually

No documents have been uploaded by study researchers.

Documents added automatically

Source	Title	Year of Publication	DOI
Embase	A Randomized, Double-Masked, Placebo-Controlled Clinical Trial of Two Forms of Omega-3 Supplements for Treating Dry Eye Disease.	2017	https://dx.doi.org/10.1016/j.ophtha.2016.09.023
Embase	Oral omega-3 supplementation lowers intraocular pressure in normotensive adults.	2018	https://dx.doi.org/10.1167/tvst.7.3.1

N.B. These documents automatically identified may not have been verified by the study sponsor.

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Documents added manually

Documents added automatically