Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12621000336886
Ethics application status
Approved
Date submitted
29/01/2021
Date registered
24/03/2021
Date last updated
23/02/2023
Date data sharing statement initially provided
24/03/2021
Date results information initially provided
23/02/2023
Type of registration
Prospectively registered

Titles & IDs
Public title
The effect of Optimel Manuka+ Dry Eye Drops with adjunctive treatment on signs and symptoms of dry eye
Scientific title
Effect on tear film properties and dry eye signs and symptoms of having an adjunctive treatment of treatments of Optimel Manuka Dry Eye Drops with the Bruder Eye Compress compared with Optimel Manuka Dry Eye Drops alone after four weeks of daily use in adults
Secondary ID [1] 303143 0
None
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Dry eye disease 320253 0
Condition category
Condition code
Eye 318186 318186 0 0
Diseases / disorders of the eye

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Optimel Antibacterial Manuka + Eye Drops 10mL (ARTG ID: 199785) contains standardised 16% antibacterial Manuka honey developed from Leptospermum sp, sodium chloride, and benzoic acid. It is available on the Australian market without prescription required.

ARTG Public Summary documentation:
https://www.ebs.tga.gov.au/servlet/xmlmillr6?dbid=ebs/PublicHTML/pdfStore.nsf&docid=199785&agid=(PrintDetailsPublic)&actionid=1

The Bruder Moist Heat Eye Compress are warm compresses that are commonly used as an easy way to treat chronic dry eye, MGD and Blepharitis. The compresses are applied over closed eyes for 10 minutes after heating it for 20 seconds in the microwave.

ARTG Public Summary documentation:
https://www.ebs.tga.gov.au/servlet/xmlmillr6?dbid=ebs/PublicHTML/pdfStore.nsf&docid=223316&agid=(PrintDetailsPublic)&actionid=1

All products to be used for this study will follow all the conditions as set out in the ARTG public summary documentation.

Participants allocated to the intervention group will administer both the eye drops and the warm compress twice daily for approximately 4 weeks. Participants will be instructed to apply the Bruder Moist Heat Eye Compresses for 10 minutes and then instil 1 drop of the Optimel Manuka+ Dry Eye Drops to each eye after an interval of 5 minutes. Participants will be asked to return for final evaluation and study exit (Visit 2) after approximately 4 weeks of daily use.
Compliance: Compliance will be monitored by measuring and recording the weight of about 10 eye drop bottles to obtain an average weight prior to giving it to the participant, and at the beginning of visit 2. Warm compresses will be checked for compliance by directly asking the participants at Visit 2, and the unmasked investigator will schedule a phone call reminder 2 weeks after the first visit to both groups to check compliance with their treatments.
Intervention code [1] 319446 0
Treatment: Devices
Intervention code [2] 319447 0
Treatment: Other
Comparator / control treatment
Optimel Antibacterial Manuka + Eye Drops 10mL (ARTG ID: 199785) contains standardised 16% antibacterial Manuka honey developed from Leptospermum sp, sodium chloride, and benzoic acid. It is available on the Australian market without prescription required.

ARTG Public Summary documentation:
https://www.ebs.tga.gov.au/servlet/xmlmillr6?dbid=ebs/PublicHTML/pdfStore.nsf&docid=199785&agid=(PrintDetailsPublic)&actionid=1


Participants allocated to the control group will administer only the eye drops. Participants will be instructed to instil 1 drop of the Optimel Manuka+ Dry Eye Drops to each eye twice daily and asked to return for final evaluation and study exit (Visit 2) after approximately 4 weeks of daily use.
Compliance: Compliance will be monitored by measuring and recording the weight of about 10 eye drop bottles to obtain an average weight prior to giving it to the participant, and at the beginning of visit 2. The unmasked investigator will schedule a phone call reminder 2 weeks after the first visit to both groups to check compliance with their treatments.
Control group
Active

Outcomes
Primary outcome [1] 326334 0
The primary endpoint is a measurable difference in tear break-up time between Optimel Manuka+ eye drops and adjunctive therapy after 4 weeks of daily use.
Fluorescein tear break-up time (TBUT; sec) (Opti-Strip-FL, Optimed, Lane Cove West, NSW, Australia) was measured viewed with a yellow Wratten filter (No. 12, Kodak) and cobalt light of the slit lamp biomicroscope. Three consecutive TBUT measurements for each eye were taken by a single masked investigator.
Timepoint [1] 326334 0
After 4 weeks of daily use
Secondary outcome [1] 391079 0
A measurable difference in lipid layer thickness
LipiView II Ocular Surface Interferometer (TearScience) will be used to measure the absolute thickness of the tear film lipid layer. The participant’s eye is positioned in front of an illumination source that is directed toward the tear film on the corneal surface. The camera records a 20-second video of the tear film interference and subsequently displays a value in interferometric colour units (ICU), where 1 ICU approximates 1nm of lipid layer thickness.
Timepoint [1] 391079 0
After 4 weeks of daily use
Secondary outcome [2] 392280 0
A measurable difference in tear evaporation rate
The Modified Vapometer is a closed chamber device which is used for measuring transepidermal water loss. Participants will be seated upright on a chair and provided with a distance fixation target. To minimize the effect of skin evaporation, petroleum jelly (Vaseline, http://www.unilever.com.au/brands-in-action/detail/Vaseline/299339/) will be applied over the upper eyelid and the surrounding areas. The VapoMeter will then be placed over the eye and a non-invasive measurement of tear evaporation will be taken within 10 s. Participants will be instructed not to blink during open eye measurement and to maintain a normal straight gaze at the fixation target. Evaporation rates with the eyes closed will also be taken, in order to account for the skin evaporation from eyelids and surrounding skin tissue. Three sets of measurement will be taken for open and closed eyes, alternating between open and closed eyes. A photo capturing the anterior eye will also be taken for ocular surface area calculation.
Timepoint [2] 392280 0
After 4 weeks of daily use
Secondary outcome [3] 392281 0
A measurable difference in subjective questionnaire - Ocular surface disease index
The Ocular Surface Disease Index (OSDI) dry eye questionnaire evaluated dry eye severity on a scale of 0 to 100, with higher scores representing greater severity of dry eye.
Timepoint [3] 392281 0
After 4 weeks of daily use

Eligibility
Key inclusion criteria
• Able to read and comprehend English and give informed consent as demonstrated by signing a record of informed consent;
• General population aged 18 years and over;
• In good general health;
• Subjectively experiencing dry eye symptoms (e.g. burning, irritation, and discomfort due to dryness of the eye or exposure to wind or sun). Participants will be selected based on a minimum OSDI score of 13 points.
• Have not used Optimel Manuka+ Dry Eye Drops in the past 3 months
• Have not used warm compresses or lid scrubs in the past 1 month
• Participant is willing to discontinue their current use of any rewetting/lubricating drops 3 days before the study and throughout the study;
• Willing to comply with the dosage and study visit schedule as directed by the investigator;
• Willing to notify the study investigator if instructed to alter their dietary intake of fish or omega-3 supplements by health/medical practitioner;
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
• Allergy to benzoic acid preservatives;
• Allergy to honey products;
• Active anterior eye disease/ infection, inflammation/allergy that requires ocular medical treatment;
• Eye injury or surgery in the past 6 months including chemical burns, penetrating injuries, traumatic iritis, orbital fractures, laser surgery, strabismus surgery, cataract or any other intraocular surgeries;
• Soft contact lens wearer within one week prior to the study and during the study.
• Rigid gas permeable, orthokeratology lens wear within 1 month prior to the study and during the study.
• Current typical dietary intake of fish or oral supplements known to have anti-inflammatory properties;
• Use of any of the following medications (including steroids) up to 12 weeks prior to start of the study or during the course of the study:
o Ocular medication, category S3 and above;
o Any systemic or topical medications that will affect ocular physiology e.g. anti-acne medications such as Roaccutane and corticosteroid or immunosuppressant medications such as Hydrocortisone, Prednisolone and antihistamine medications such as Claritine;
• Any systemic disease that may affect ocular health e.g. Graves disease, and auto-immune diseases such as ankylosing spondylitis, multiple sclerosis and systemic lupus erythematosus;
• Epilepsy or history of migraines exacerbated by flashing, strobe-like lights;
• The Investigator may, at his/her discretion, exclude anyone else who they believe may not be able to fulfil the study requirements, or if it is believed to be in the participant’s best interests.

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)
To ensure that each participant has an equal chance of being placed in any group to start with (Optimel Manuka+ Dry Eye Drops with warm compresses or Optimel Manuka+ Dry Eye Drops alone), a computer allocates each study participant into a group randomly, like the flip of a coin. Once randomised participants will be allocated to one of the participant groups. The randomisation schedule will only be accesible by the unmasked investigator, and the unmasked investigator will provide instructions to the study participants as to the drop instillation technique and eye mask heating instruction and use. The masked investigator responsible for performing objective measurements will not be cognizant to the randomisation schedule and will not be present during the dispensing of the drops to maintain masking.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Eligible participants will be assigned into their treatment group according to a randomization table generated using ((https://www.randomizer.org/), which will occur in chronological order of study enrolments.
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?


The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Not Applicable
Type of endpoint/s
Efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
1/04/2021
Actual
9/03/2022
Date of last participant enrolment
Anticipated
30/07/2022
Actual
14/09/2022
Date of last data collection
Anticipated
31/08/2022
Actual
14/10/2022
Sample size
Target
32
Accrual to date
Final
34
Recruitment in Australia
Recruitment state(s)
NSW

Funding & Sponsors
Funding source category [1] 307547 0
University
Name [1] 307547 0
UNSW Sydney
Country [1] 307547 0
Australia
Primary sponsor type
University
Name
UNSW Sydney
Address
School of Optometry & Vision Science, UNSW Sydney, NSW 2052
Country
Australia
Secondary sponsor category [1] 308237 0
None
Name [1] 308237 0
Address [1] 308237 0
Country [1] 308237 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 307613 0
UNSW HREC Committee
Ethics committee address [1] 307613 0
UNSW Sydney
NSW 2052 Australia
Ethics committee country [1] 307613 0
Australia
Date submitted for ethics approval [1] 307613 0
29/01/2021
Approval date [1] 307613 0
16/04/2021
Ethics approval number [1] 307613 0
HC210034

Summary
Brief summary
Manuka honey has a positive effect on enhancing the body’s natural immune responses due to its anti-inflammatory and antioxidant properties. Its antibacterial property is useful for wound healing and the prevention of inflammation. Other than the antibacterial property, manuka honey also showed to have antioxidant and anti-cancer properties. Multiple clinical trials have concluded its effectiveness against various ocular conditions: blepharitis, contact lens related dry eyes, and Meibomian Gland Dysfunction.

The Optimel Manuka+ Dry Eye Drops packaging claimed: “For use as an adjunctive therapy in addition to good eyelid hygiene”.("Optimel Manuka+ Dry Eye Drops", 2020) However, the effectiveness of the Optimel Manuka+ Dry Eye Drops with the addition of eyelid hygiene therapies has not previously been investigated. Therefore, it is worthwhile to conduct a thorough investigation on this potential adjunctive treatment by measuring both the subjective and objective parameters associated with dry eye disease.

Thus, this study will be a randomized clinical trial comparing the effectiveness of conventional adjunctive treatment (warm compresses) in combination with Optimel Manuka+ Dry Eye Drops on dry eye disease compared to the eye drops alone. This study will include at least 40 participants who experience dry eye, where they are randomly assigned into two groups receiving the combination therapy of warm compresses plus Optimel Manuka+ Dry Eye Drops or Optimel Manuka+ Dry Eye Drops only, where eye drops will be applied two times daily (Albietz & Schmid, 2017) in both eyes for one month. Optimel Manuka+ Dry Eye Drops are commercially available in Australia, therefore the results of this study will provide an evidenced based dry eye therapy option for society to consider.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 107866 0
Dr Jacqueline Tan-Showyin
Address 107866 0
Level 3 North Wing Rupert Myers Building, Gate 14 Barker Street, UNSW Sydney NSW 2052 Australia
Country 107866 0
Australia
Phone 107866 0
+61 2 93856551
Fax 107866 0
Email 107866 0
[email protected]
Contact person for public queries
Name 107867 0
Dr Jacqueline Tan-Showyin
Address 107867 0
Level 3 North Wing Rupert Myers Building, Gate 14 Barker Street, UNSW Sydney NSW 2052 Australia
Country 107867 0
Australia
Phone 107867 0
+61 2 93856551
Fax 107867 0
Email 107867 0
[email protected]
Contact person for scientific queries
Name 107868 0
Dr Jacqueline Tan-Showyin
Address 107868 0
Level 3 North Wing Rupert Myers Building, Gate 14 Barker Street, UNSW Sydney NSW 2052 Australia
Country 107868 0
Australia
Phone 107868 0
+61 2 93856551
Fax 107868 0
Email 107868 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment


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
No additional documents have been identified.