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Trial registered on ANZCTR


Registration number
ACTRN12625000028404p
Ethics application status
Submitted, not yet approved
Date submitted
29/10/2024
Date registered
15/01/2025
Date last updated
15/01/2025
Date data sharing statement initially provided
15/01/2025
Type of registration
Prospectively registered

Titles & IDs
Public title
Evaluation of a new biomarker for tear film health
Scientific title
Evaluation of a new biomarker for tear film health in individuals with tear dysfunction
Secondary ID [1] 313138 0
None
Universal Trial Number (UTN)
U1111-1314-2337
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Aqueous-deficient dry eye 335403 0
Meibomian gland dysfunction 335586 0
Condition category
Condition code
Eye 331970 331970 0 0
Diseases / disorders of the eye

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Intervention 1: Prednisolone Sodium Phosphate 0.5% 5mg/mL eye drops minims (Bausch & Lomb Australia Pty Ltd)
Mode: topical ocular.
Dose: one drop, both eyes, four times daily, self-administered by the participant.
Duration: 14 days, ± 2 days.
Treatment adherence will be monitored by the use of an at-home treatment tracking diary.

Intervention 2: LipiFlow Thermal Pulsation (Johnson & Johnson Pty Ltd)
Single dose of standard in-office standard therapy of 12 minutes duration, both eyes simultaneously.
Administered by the study optometrist at day 14 ± 2 only to participants who do not show a clinical improvement in signs of dry eye ("treatment non-responders") after 14 days of treatment with Prednisolone Sodium Phosphate 0.5% 5mg/mL or placebo (saline (sodium chloride) 0.9%).

Acoustically-driven microfluidic extensional rheometry: The novel extensional rheometry platform is a laboratory-based platform that can be used to analyse the rheological (stretching) properties of a tear sample. Tear samples collected from study participants are analysed on the platform at all study visits for all participants. The tear rheological analysis generated by the platform is a primary outcome of this study.

Eligible participants will be assessed at baseline to be classified as being in one of two subgroups (aqueous-deficient dry eye or meibomian gland dysfunction) for the purposes of endpoint analysis and treatment response. All study procedures and interventions will be the same for participants in both subgroups.

"Treatment responders" will exit the study after Day 14. "Treatment non-responders" will receive LipiFlow Thermal Pulsation at Day 14, as described above, and be re-assessed for treatment response at Day 42. Treatment ‘responders’ in the aqueous-deficient dry eye subgroup will be defined as individuals who show greater than or equal to 3 units improvement (NEI scale) in overall corneal fluorescein staining in the study eye. Treatment ‘responders’ in the meibomian gland dysfunction subgroup will be defined as those with an absolute MGYLS score of greater than or equal to 5 or a MGS of greater than or equal to 15 in the study eye.
Intervention code [1] 329713 0
Treatment: Drugs
Intervention code [2] 329714 0
Treatment: Devices
Intervention code [3] 329964 0
Diagnosis / Prognosis
Comparator / control treatment
Saline (sodium chloride) 0.9% eye drops minims (Bausch & Lomb Pty Ltd)
Mode: topical ocular.
Dose: one drop, both eyes, four times daily, self-administered by the participant.
Duration: 14 days, ± 2 days.
Treatment adherence will be monitored by the use of an at-home treatment tracking diary.

"Treatment responders" will exit the study after Day 14. "Treatment non-responders" will receive LipiFlow Thermal Pulsation at Day 14, as described above, and be re-assessed for treatment response at Day 42. Treatment ‘responders’ in the aqueous-deficient dry eye subgroup will be defined as individuals who show greater than or equal to 3 units improvement (NEI scale) in overall corneal fluorescein staining in the study eye. Treatment ‘responders’ in the meibomian gland dysfunction subgroup will be defined as those with an absolute MGYLS score of greater than or equal to 5 or a MGS of greater than or equal to 15 in the study eye.

Intervention 2: LipiFlow Thermal Pulsation (Johnson & Johnson Pty Ltd)
Single dose of standard in-office standard therapy of 12 minutes duration, both eyes simultaneously.
Administered by the study optometrist at day 14 ± 2 only to participants who do not show a clinical improvement in signs of dry eye ("treatment non-responders") after 14 days of treatment with Prednisolone Sodium Phosphate 0.5% 5mg/mL or placebo (saline (sodium chloride) 0.9%).
Control group
Placebo

Outcomes
Primary outcome [1] 339646 0
Change in tear aqueous-specific rheology attributes (all participants).
Timepoint [1] 339646 0
Baseline (all participants), Day 14 ± 2 post-intervention commencement (primary timepoint, all participants), Day 42 ± 3 post-intervention commencement (Treatment non-responder participants at Day 14)
Primary outcome [2] 339647 0
Change in total corneal fluorescein staining score (aqueous-deficient dry eye group only).
Timepoint [2] 339647 0
Baseline (all participants), Day 14 ± 2 post-intervention commencement (primary timepoint, all participants), Day 42 ± 3 post-intervention commencement (Treatment non-responder participants at Day 14)
Primary outcome [3] 339648 0
Change in meibomian gland secretions (meibomian gland dysfunction group only).
Timepoint [3] 339648 0
Baseline (all participants), Day 14 ± 2 post-intervention commencement (primary timepoint, all participants), Day 42 ± 3 post-intervention commencement (Treatment non-responder participants at Day 14)
Secondary outcome [1] 440720 0
Change in OSDI score
Timepoint [1] 440720 0
Baseline (all participants), Day 14 ± 2 post-intervention commencement (all participants), Day 42 ± 3 post-intervention commencement (Treatment non-responder participants at Day 14)
Secondary outcome [2] 440721 0
Change in SPEED score
Timepoint [2] 440721 0
Baseline (all participants), Day 14 ± 2 post-intervention commencement (all participants), Day 42 ± 3 post-intervention commencement (Treatment non-responder participants at Day 14)
Secondary outcome [3] 440723 0
Change in tear MMP-9 result
Timepoint [3] 440723 0
Baseline (all participants), Day 14 ± 2 post-intervention commencement (all participants), Day 42 ± 3 post-intervention commencement (Treatment non-responder participants at Day 14)
Secondary outcome [4] 440724 0
Change in central corneal fluorescein staining score
Timepoint [4] 440724 0
Baseline (all participants), Day 14 ± 2 post-intervention commencement (all participants), Day 42 ± 3 post-intervention commencement (Treatment non-responder participants at Day 14)
Secondary outcome [5] 440725 0
Change in conjunctival hyperaemia
Timepoint [5] 440725 0
Baseline (all participants), Day 14 ± 2 post-intervention commencement (all participants), Day 42 ± 3 post-intervention commencement (Treatment non-responder participants at Day 14)
Secondary outcome [6] 440726 0
Change in conjunctival lissamine green staining score
Timepoint [6] 440726 0
Baseline (all participants), Day 14 ± 2 post-intervention commencement (all participants), Day 42 ± 3 post-intervention commencement (Treatment non-responder participants at Day 14)
Secondary outcome [7] 440727 0
Change in non-invasive tear break-up time (NITBUT)
Timepoint [7] 440727 0
Baseline (all participants), Day 14 ± 2 post-intervention commencement (all participants), Day 42 ± 3 post-intervention commencement (Treatment non-responder participants at Day 14)
Secondary outcome [8] 440728 0
Change in tear meniscus height (TMH)
Timepoint [8] 440728 0
Baseline (all participants), Day 14 ± 2 post-intervention commencement (all participants), Day 42 ± 3 post-intervention commencement (Treatment non-responder participants at Day 14)
Secondary outcome [9] 440729 0
Change in Schirmer test score
Timepoint [9] 440729 0
Baseline (all participants), Day 14 ± 2 post-intervention commencement (all participants), Day 42 ± 3 post-intervention commencement (Treatment non-responder participants at Day 14)
Secondary outcome [10] 440730 0
The percentage of eyes with an increase of greater than or equal to 10 mm/5 min in Schirmer test score (aqueous-deficient dry eye group only)
Timepoint [10] 440730 0
Baseline (all participants), Day 14 ± 2 post-intervention commencement (all participants), Day 42 ± 3 post-intervention commencement (Treatment non-responder participants at Day 14)
Secondary outcome [11] 440731 0
Change in meibomian glands yielding liquid secretion (MGYLS) score
Timepoint [11] 440731 0
Baseline (all participants), Day 14 ± 2 post-intervention commencement (all participants), Day 42 ± 3 post-intervention commencement (Treatment non-responder participants at Day 14)
Secondary outcome [12] 440732 0
The percentage of eyes with an MGYLS score of greater than or equal to 5 (meibomian gland dysfunction group only)
Timepoint [12] 440732 0
Baseline (all participants), Day 14 ± 2 post-intervention commencement (all participants), Day 42 ± 3 post-intervention commencement (Treatment non-responder participants at Day 14)
Secondary outcome [13] 440733 0
Change in meibomian gland score (MGS)
Timepoint [13] 440733 0
Baseline (all participants), Day 14 ± 2 post-intervention commencement (all participants), Day 42 ± 3 post-intervention commencement (Treatment non-responder participants at Day 14)
Secondary outcome [14] 440734 0
The percentage of eyes with an MGS score of greater than or equal to 15 (meibomian gland dysfunction group only)
Timepoint [14] 440734 0
Baseline (all participants), Day 14 ± 2 post-intervention commencement (all participants), Day 42 ± 3 post-intervention commencement (Treatment non-responder participants at Day 14)
Secondary outcome [15] 440735 0
Change in tear lipid layer thickness
Timepoint [15] 440735 0
Baseline (all participants), Day 14 ± 2 post-intervention commencement (all participants), Day 42 ± 3 post-intervention commencement (Treatment non-responder participants at Day 14)
Secondary outcome [16] 440737 0
Exploratory outcome: Change in tear cytokine levels
Timepoint [16] 440737 0
Baseline (all participants), Day 14 ± 2 post-intervention commencement (all participants), Day 42 ± 3 post-intervention commencement (Treatment non-responder participants at Day 14)
Secondary outcome [17] 441806 0
*Primary outcome: Change in meibomian gland secretions (meibomian gland dysfunction group only).
Timepoint [17] 441806 0
Baseline (all participants), Day 14 ± 2 post-intervention commencement (primary timepoint, all participants), Day 42 ± 3 post-intervention commencement (Treatment non-responder participants at Day 14)
Secondary outcome [18] 441886 0
Change in "burning/stinging sensation" symptom score
Timepoint [18] 441886 0
Baseline (all participants), Day 14 ± 2 post-intervention commencement (all participants), Day 42 ± 3 post-intervention commencement (Treatment non-responder participants at Day 14)
Secondary outcome [19] 441887 0
Change in "itching" symptom score
Timepoint [19] 441887 0
Baseline (all participants), Day 14 ± 2 post-intervention commencement (all participants), Day 42 ± 3 post-intervention commencement (Treatment non-responder participants at Day 14)
Secondary outcome [20] 441888 0
Change in "foreign body sensation" symptom score
Timepoint [20] 441888 0
Baseline (all participants), Day 14 ± 2 post-intervention commencement (all participants), Day 42 ± 3 post-intervention commencement (Treatment non-responder participants at Day 14)
Secondary outcome [21] 441889 0
Change in "eye discomfort" symptom score
Timepoint [21] 441889 0
Baseline (all participants), Day 14 ± 2 post-intervention commencement (all participants), Day 42 ± 3 post-intervention commencement (Treatment non-responder participants at Day 14)
Secondary outcome [22] 441890 0
Change in "eye dryness" symptom score
Timepoint [22] 441890 0
Baseline (all participants), Day 14 ± 2 post-intervention commencement (all participants), Day 42 ± 3 post-intervention commencement (Treatment non-responder participants at Day 14)
Secondary outcome [23] 441891 0
Change in "photophobia" symptom score
Timepoint [23] 441891 0
Baseline (all participants), Day 14 ± 2 post-intervention commencement (all participants), Day 42 ± 3 post-intervention commencement (Treatment non-responder participants at Day 14)
Secondary outcome [24] 441892 0
Change in "pain" symptom score
Timepoint [24] 441892 0
Baseline (all participants), Day 14 ± 2 post-intervention commencement (all participants), Day 42 ± 3 post-intervention commencement (Treatment non-responder participants at Day 14)

Eligibility
Key inclusion criteria
1. Male or female, aged at least 18 years of age;
2. Provide written informed consent and documentation, in accordance with privacy requirements, obtained prior to performing any study procedures;
3. Ability to understand and follow study instruction, with the intention of completing all of the required study visits.
4. Have a stable artificial tear dosage regimen for at least 30 days prior to Visit 1.
5. Have a stable regime of non-heat based, self-administered eyelid hygiene for at least 30 days prior to Visit 1.

The following inclusion criteria apply only to the aqueous deficient-dry eye subgroup:
1. OSDI score greater than or equal to 13, AND:
In at least one eye (where if both eyes are eligible, the eye with worse (higher) corneal fluorescein staining will be deemed the ‘study eye’; if both eyes have the same fluorescein staining score, the right eye will be the study eye):
2. TMH less than or equal to 0.2mm OR Schirmer test score with anaesthesia less than or equal to 5mm/5 minutes; and
3. Overall corneal fluorescein staining score of greater than or equal to 5 using the NEI scale (Lemp 1995); and
4. Conjunctival hyperaemia (bulbar redness score (greater than or equal to 1) using the Efron scale); and
5. MGS greater than 12.

The following inclusion criteria apply only to the meibomian gland dysfunction subgroup:
1. OSDI score less than or equal to 32, AND:
In at least one eye (where if both eyes are eligible, the eye with the worse (lower) MGS score will be deemed the ‘study eye’; if both eyes have the same MGS score, the right eye will be the study eye):
2. Meibomian gland score (MGS) less than or equal to 12 (assessed using the Meibomian Gland Evaluator, Korb and Blackie 2008); and
3. Non-invasive tear break-up time (NITBUT) less than or equal to 10 seconds; and
4. Overall corneal fluorescein staining score of less than 3 using the NEI grading scale.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Known hypersensitivity or contraindication to any of the study procedures, interventions or their components.
2. Anticipated change in habitual artificial tear use (type/frequency) over the course of the study. Note: Participants must have had a stable artificial tear dosage regimen for at least 30 days prior to Visit 1 to be eligible.
3. Anticipated change in non-heat based, self-administered eyelid hygiene regimen over the course of the study. Note: Participants must have had a stable regime for this form of therapy at least 30 days prior to Visit 1 to be eligible.
4. Within 30 days of Visit 1, or anticipated required use throughout the study period:
a. Topical ophthalmic corticosteroids;
b. Other topical ophthalmic anti-inflammatory medications, such as Restasis, Cequa or Xiidra;
c. Topical, systemic or nasal anti-histamines;
d. Topical ophthalmic IOP-lowering medications;
e. Topical investigational ophthalmic drugs or devices;
f. Contact lenses;
g. Warm compresses or other heat-based eyelid therapy;
h. Systemic or nasal corticosteroids;
i. Systemic immunomodulatory medications.
5. Within 90 days of Visit 1, have received intense pulsed light (IPL), LipiFlow, or another similar treatment for dry eye disease.
6. Ocular surgery or trauma in either eye within the past 90 days.
7. Planned ocular surgery in either eye during the study period.
8. Within 90 days of Visit 1, or anticipated throughout the study period, use of high-dose omega-3 supplements (defined as combined daily dose of greater than or equal to 3000mg EPA + DHA).
9. Current use of punctal plugs, their anticipated insertion during the study, or a history of punctal cautery in either eye at any time prior to Visit 1, or anticipated use during the study period.
10. Current active ocular infection.
11. Current use of eyelash extensions, or anticipated use throughout the study period.
12. History of herpetic eye disease.
13. History of glaucoma or ocular hypertension.
14. IOP >24mmHg in either eye at Visit 1.
15. Documented history of steroid-induced IOP responsiveness.
16. At Visit 1, experience more than two occurrences of reflex tearing during basal tear collection in a single eye.
17. In the opinion of the investigator, be unable to adhere to the trial protocol or unable to successfully instil eye drops.
18. Currently pregnant or breastfeeding, or planning to become pregnant over the course of the study.
19. History of a systemic infection known to affect eye health (e.g., positive for COVID-19, or a upper respiratory infection within 4 weeks of Visit 1), by self-report.

Study design
Purpose of the study
Diagnosis
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Numbered containers
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Computerised sequence generation
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
Not Applicable
Type of endpoint/s
Efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
20/01/2025
Actual
Date of last participant enrolment
Anticipated
25/08/2025
Actual
Date of last data collection
Anticipated
18/10/2025
Actual
Sample size
Target
60
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
VIC

Funding & Sponsors
Funding source category [1] 317580 0
University
Name [1] 317580 0
The University of Melbourne
Country [1] 317580 0
Australia
Primary sponsor type
University
Name
The University of Melbourne
Address
Country
Australia
Secondary sponsor category [1] 319985 0
None
Name [1] 319985 0
Address [1] 319985 0
Country [1] 319985 0

Ethics approval
Ethics application status
Submitted, not yet approved
Ethics committee name [1] 316286 0
University of Melbourne Central Human Research Ethics Committee
Ethics committee address [1] 316286 0
https://research.unimelb.edu.au/work-with-us/ethics-and-integrity/our-ethics-committees
Ethics committee country [1] 316286 0
Australia
Date submitted for ethics approval [1] 316286 0
13/10/2024
Approval date [1] 316286 0
Ethics approval number [1] 316286 0

Summary
Brief summary
As the most common indication for seeking medical eye care in developed countries, tear dysfunction is a major public health issue. The most common form of tear dysfunction is dry eye disease.

At present, major barriers to optimal dry eye medical care are difficulties in reliably diagnosing and assessing the severity of the condition. There is therefore a need for new, rapid, cost-effective methods for detecting and staging dry eye, and tear dysfunction more generally, in clinical practice.

This study seeks to evaluate a new method for analysing tear health, based upon quantifying biophysical attributes related to tear viscoelasticity, using a novel acoustically-driven microfluidic extensional rheometry platform.

This study seeks to assess the therapeutic responsivity of the new method by examining correlations between the changes to dry eye clinical signs and ADMiER-derived tear rheology attributes, in response to established interventions for dry eye. We hypothesise that the viscoelastic properties of the tears will correlate to changes in the clinical signs and symptoms of dry eye disease.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 137402 0
Prof Laura Downie
Address 137402 0
Department of Optometry and Vision Sciences, Faculty of Medicine, Dentistry and Health Sciences, The University of Melbourne, 200 Berkeley Street, Carlton, Victoria 3053
Country 137402 0
Australia
Phone 137402 0
+61 3 9035 3043
Fax 137402 0
Email 137402 0
[email protected]
Contact person for public queries
Name 137403 0
Laura Downie
Address 137403 0
Department of Optometry and Vision Sciences, Faculty of Medicine, Dentistry and Health Sciences, The University of Melbourne, 200 Berkeley Street, Carlton, Victoria 3053
Country 137403 0
Australia
Phone 137403 0
+61 3 9035 3043
Fax 137403 0
Email 137403 0
[email protected]
Contact person for scientific queries
Name 137404 0
Laura Downie
Address 137404 0
Department of Optometry and Vision Sciences, Faculty of Medicine, Dentistry and Health Sciences, The University of Melbourne, 200 Berkeley Street, Carlton, Victoria 3053
Country 137404 0
Australia
Phone 137404 0
+61 3 9035 3043
Fax 137404 0
Email 137404 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.