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Trial registered on ANZCTR


Registration number
ACTRN12621000520831
Ethics application status
Approved
Date submitted
25/01/2021
Date registered
4/05/2021
Date last updated
8/11/2022
Date data sharing statement initially provided
4/05/2021
Type of registration
Prospectively registered

Titles & IDs
Public title
The behaviour of and change to immune cells in the cornea when anti-inflammatory and immunosuppressant eye drops are topically applied into the eye of healthy individuals.
Scientific title
The behaviour of and change to corneal dendritic cell dynamics before and after anti-inflammatory and immunosuppressant eye drops are topically applied into the eye of healthy individuals.
Secondary ID [1] 303256 0
None
Universal Trial Number (UTN)
U1111-1264-1617
Trial acronym
CDC
Linked study record

Health condition
Health condition(s) or problem(s) studied:
autoimmune eye disorders 320435 0
Condition category
Condition code
Eye 318333 318333 0 0
Normal eye development and function
Inflammatory and Immune System 318334 318334 0 0
Normal development and function of the immune system

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
The primary objective of the study is to determine immune cell dynamics before and after the use of topical anti-inflammatory and immunosuppressive eyedrops. This intervention will determine if presumed immune cells with morphological characteristics of resident corneal dendritic cells, as observed in a time-lapsed manner using In vivo confocal microscopy are indeed immune cells of the cornea.

All ocular topical medication chosen in the study is carefully selected from eye care professionals considering less participant risk and better safety profiles for each drug category.
A total of 90 healthy individuals will be randomly assigned to one of the three groups of approximately 30 each. The participant will be masked to group assignment. The clinician that will be administering the treatment cannot be masked due to differences in the drug packaging. All other study personnel that will be assessing the outcomes and analysing the results/data will be masked.

Group one will act as the control group.
Group two will receive a single drop of ocular anti-inflammatory eye drops: FLUCON® Eye Drops 0.1% (fluorometholone— Flucon®, Alcon Laboratories Pty. Ltd., Fort Worth, TX, USA)
Flucon eye drops are used to treat the redness, swelling, and other symptoms of eye inflammation. Flucon eye drops contain the active ingredient fluorometholone acetate. Fluorometholone belongs to a class of medicines known as "steroids" or "corticosteroids" which reduce inflammation. The active drug is fluorometholone (1 mg/mL). A qualified optometrist will be applying the drops to the right eye of eligible participants after ocular evaluation using confocal microscopy.

Group three will receive a single drop of immunosuppressive eye drop: XIIDRA® Lifitegrast 50 mg/mL eye drops, single-dose containers solution (NOVARTIS Pharmaceuticals Australia Pty Limited) XIIDRA is an eye drop containing the medicine lifitegrast. Lifitegrast is a type of medicine called an 'LFA-1 antagonist' (LFA-1 stands for 'lymphocyte function-associated antigen-1'). It is used to treat moderate to severe dry eye disease in adults for whom prior use of artificial tears has not been sufficient. It works by decreasing inflammation in dry eye disease. A qualified optometrist will be applying the drops to the right eye of eligible participants after ocular evaluation using confocal microscopy.

Note that most side effects of the topical eye drops used in the study are likely reported only in prolonged drug exposure. Only a single eyedrop will be applied during the one visit of the study. Ocular surface absorption is less than 10% of the dose. Systemic side effects of medication are minimal due to mechanisms of ocular drug absorption (absorption occurs directly into the eye before reaching the systemic circulation).
Intervention code [1] 319559 0
Treatment: Drugs
Comparator / control treatment
Group one will act as the control group. A single drop of Saline solution: Sodium Chloride 0.9% Pfizer will be applied before and after in vivo confocal microscopy. This type of eye solution is indicated for ocular irrigation or eyewash. Each mL contains a source of sodium ions (154 mmol/L), chloride ions (154 mmol/L) and water. A qualified optometrist will be applying the drops to the right eye of eligible participants after ocular evaluation using confocal microscopy.
Control group
Placebo

Outcomes
Primary outcome [1] 326301 0
The impact of topical anti-inflammatory and immunosuppressant agents on corneal dendritic cell dynamics. This is a composite primary outcome in that a number of measures that characterise cell dynamics are included; trajectory speed, displacement speed, and persistence. These will be analyzed using two-dimensional maximum projection images obtained with in vivo confocal microscopy and analyzed on ImageJ software (version 1.52d; National Institute of Health, USA).
Timepoint [1] 326301 0
baseline, 15 mins after eye drop administration
Secondary outcome [1] 393284 0
The impact of topical anti-inflammatory and immunosuppressant agents on corneal dendritic cell morphology.. This is a composite secondary outcome in that a number of measures that characterise cell morphology are included: dendritic cell density, field area, circularity, and dendritic complexity. These parameters will be analyzed using two-dimensional maximum projection images obtained with in vivo confocal microscopy and analyzed on ImageJ software (version 1.52d; National Institute of Health, USA).
Timepoint [1] 393284 0
15 mins after eye drop administration

Eligibility
Key inclusion criteria
Participants must satisfy the following conditions prior to inclusion in the study:
A) Aged at least 18 years
B) Good ocular health
C) Willing and able to comply with protocol (e.g. attend study visit)
D) Existing wearers should discontinue lens wear for at least 24 hours prior to examination.
E) Participants without dry eye will be included.
F) Former contact lens wearers will be included
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
Any of the following will render a participant ineligible for inclusion:
A) Current pregnancy, breastfeeding or traying to become pregnant
B) History of ocular trauma or surgery such as LASIK or PRK
C) Current or long-term use of topical ocular medication
D) Ocular disease or systemic disease that may affect the cornea or conjunctiva (epithelial defects, ulcers and corneal epithelial or basement membrane dystrophies).
E) Use of orthokeratology contact lenses within the past 3 months
G) Use of soft contact lenses in either eye within 1 month of the study or rigid gas permeable contact lenses within 3 months of the study
H) Dry eye disease (defined as defined as a 5-Item dry eye questionnaire (DEQ-5) score equal to 7.
AND failing at least one of the objective dry eye tests Non-Invasive Break-Up Time with less than or equal to 10s, or Corneal Fluorescein Staining with greater than or equal to 5 corneal spots.
(Note: both eyes will be assessed, and the worst eye will contribute toward the dry eye diagnosis)
H) Allergy to fluorometholone, lifitegrast or any of the excipients of the study drugs

Study design
Purpose of the study
Prevention
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
central randomization by computer
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Simple randomization using a randomization table from a statistic book
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s

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
Given that this study is designed as a conceptual development of a novel investigation using microscopical assessment of corneal DCs to explore their dynamics, we have calculated a sample size based on previous studies with a similar design. The number of participants is based on the reported cell density and standard deviation of density without dry eye (Mobeen, et al., 2019). Sample size calculation (G*Power 3.1) to detect a difference of approximately 40 cells/mm2 at a significance level of p equal to 0.05, assuming a measurement standard deviation of plus menus (±) 32 cells/mm2, revealed that a minimum of 28 participants per group were required to be able to reject, with 90 per cent power, the null hypothesis that the population group means are equal. The minimum number of participants recruited per group is then set at 30.
The difference in cell dynamics will be measured in a number of ways, essentially by comparing the average persistence, trajectory and displacement cell speeds between the three groups. The differences between the cell dynamics obtained at baseline without the effect of the eyedrops and after 15 minutes of drug application will be measured, using appropriate analysis (ANOVA, chi-squared or T-test).

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
30/08/2021
Actual
30/08/2021
Date of last participant enrolment
Anticipated
31/12/2023
Actual
Date of last data collection
Anticipated
31/12/2023
Actual
Sample size
Target
90
Accrual to date
55
Final
Recruitment in Australia
Recruitment state(s)
QLD
Recruitment postcode(s) [1] 32822 0
4059 - Kelvin Grove

Funding & Sponsors
Funding source category [1] 307964 0
University
Name [1] 307964 0
Queensland University of Technology
Country [1] 307964 0
Australia
Primary sponsor type
University
Name
Queensland University of Technology
Address
Queensland University of Technology, 60 Musk av, Kelvin Grove QLD 4069
Country
Australia
Secondary sponsor category [1] 308680 0
None
Name [1] 308680 0
Address [1] 308680 0
Country [1] 308680 0
Other collaborator category [1] 281620 0
Hospital
Name [1] 281620 0
Princess Alexandra Hospital in Brisbane
Address [1] 281620 0
Princess Alexandra Hospital in Brisbane, 199 Ipswich Rd, Woolloongabba QLD 4102
Country [1] 281620 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 307703 0
Queensland University of Technology Human Research Ethics Committee
Ethics committee address [1] 307703 0
88 Musk Av, Kelvin Grove QLD 4059
Ethics committee country [1] 307703 0
Australia
Date submitted for ethics approval [1] 307703 0
26/10/2020
Approval date [1] 307703 0
12/02/2021
Ethics approval number [1] 307703 0
2000000721

Summary
Brief summary
The purpose of this project is to evaluate the movement of immune cells that occur naturally in the clear window at the front of the eye (the cornea). This movement will be evaluated before and after the application of commercially available eye drops used to treat sign and symptoms of mild to severe dry eye.
Immune cells with and without dendrites give the immune system the ability to sequester, tightly regulate, and increase the efficiency of defense against internal and external pathogens. Understanding the cell dynamics in healthy individuals will contribute to normative data to future studies on ocular and systemic diseases.
In addition to assessing the corneal nerves, corneal confocal microscopy is also capable of detecting dendritic cells. These cells have a distinctive hyper-reflective shape and are located at the same depth of the corneal nerves, at approximately a 50 µm depth from corneal epithelium. Hence, the assessment of these two important ocular structures in a single image offers useful insight into the association and interaction between both; the nervous and immune systems of the ocular surface.
The ability to observe and quantify migration rates of dendritic cells in vivo is likely to reveal previously unknown insights into corneal and general pathophysiology and may serve as an effective biomarker to intervention therapies. The dynamics of corneal resident dendritic cells located at the corneal sub-basal nerve plexus may provide a powerful approach to understanding the spectrum of immune and neurological diseases with applications in observational and analytic epidemiology, randomised clinical trials, screening and diagnosis and prognosis. DC dynamics have the potential to also reflect the entire spectrum of autoimmune diseases from the earliest manifestations to the terminal stages. The behaviour of these cells could potentially offer the means for homogeneous classification of autoimmune and systemic disease and risk factors, and also extend our base information about the underlying pathogenesis of immune diseases.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 108202 0
Dr Luisa Holguin Colorado
Address 108202 0
Queensland University of Technology, 60 Musk Av, Kelvin Grove , QLD 4059
Country 108202 0
Australia
Phone 108202 0
+61 7 3138 6404
Fax 108202 0
Email 108202 0
[email protected]
Contact person for public queries
Name 108203 0
Dr Katie Edwards
Address 108203 0
Queensland University of Technology, 60 Musk Av, Kelvin Grove , QLD 4059
Country 108203 0
Australia
Phone 108203 0
+61 7 3138 6154
Fax 108203 0
Email 108203 0
[email protected]
Contact person for scientific queries
Name 108204 0
Dr Luisa Holguin Colorado
Address 108204 0
Queensland University of Technology, 60 Musk Av, Kelvin Grove , QLD 4059
Country 108204 0
Australia
Phone 108204 0
+61 7 3138 6404
Fax 108204 0
Email 108204 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
As per participant consent, no disclosure of individual information will occur, however, a final brief summary of the outcomes will be provided to participants at the completion of the study.


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.