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Trial registered on ANZCTR


Registration number
ACTRN12623000012673
Ethics application status
Approved
Date submitted
5/12/2022
Date registered
9/01/2023
Date last updated
9/01/2023
Date data sharing statement initially provided
9/01/2023
Type of registration
Prospectively registered

Titles & IDs
Public title
Exploring the impact of castor oil application on the eye's surface quality
Scientific title
Randomised controlled trial to establish the impact of periocular castor oil application on ocular surface parameters and pre-ocular tear film quality in adults with blepharitis
Secondary ID [1] 308455 0
None
Universal Trial Number (UTN)
U1111-1285-1086
Trial acronym
Linked study record
This study is a follow up study to the pilot study registered as ACTRN12618000856213

Health condition
Health condition(s) or problem(s) studied:
Anterior blepharitis 328256 0
Dry eye disease 328257 0
Meibomian gland dysfunction 328258 0
Condition category
Condition code
Eye 325300 325300 0 0
Diseases / disorders of the eye

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
After training by clinical researchers, participants will be randomised to topically apply either approximately 0.2g of a proprietary cold pressed castor oil preparation or 0.2mL saline control to the external upper and lower eyelid skin surfaces close to the eyelash line.

Application will be to both the eyelids of both eyes using a dedicated 10ml vial fitted with a roller ball applicator, in which contents are obscured by opaqueness of the bottle and by bottle labelling, twice daily (morning and night) for 6 months.

Adherence to the intervention in the study will be monitored subjectively by participant-reporting via daily diary and objectively by weighing returned bottles and comparing the weight after 1 month of use to the weight on issue.
Intervention code [1] 324899 0
Treatment: Other
Comparator / control treatment
The control treatment will be saline, stored in an identical opaque glass bottle to the active (castor oil) arm

Adherence to the intervention in the study will be monitored subjectively by participant-reporting via daily diary and objectively by weighing returned bottles and comparing the weight after 1 month of use to the weight on issue.
Control group
Placebo

Outcomes
Primary outcome [1] 333165 0
Clinical anterior blepharitis grade change of 1 based on lash crusting score evaluated by slit lamp biomicroscopy
Timepoint [1] 333165 0
Baseline, 1, 2, 3 (primary timepoint) and 6 months after treatment commencement
Primary outcome [2] 333280 0
Non-invasive tear film stability change of 4 seconds as measured objectively and non-invasively using the Oculus Keratograph 5M
Timepoint [2] 333280 0
Baseline, 1, 2, 3 (primary timepoint) and 6 months after treatment commencement
Secondary outcome [1] 416011 0
Lid wiper epitheliopathy (LWE) visualised and graded (Korb scoring) using lissamine green vital dye and slit lamp biomicroscopy
Timepoint [1] 416011 0
Baseline, 1, 2, 3 and 6 months after treatment commencement
Secondary outcome [2] 416456 0
Discomfort symptoms on the Ocular Surface Disease Index (OSDI)
Timepoint [2] 416456 0
Baseline, 1, 2, 3 and 6 months after treatment commencement
Secondary outcome [3] 416457 0
Discomfort symptoms on the Standardised Patient Evaluation of Eye Dryness (SPEED) questionnaire
Timepoint [3] 416457 0
Baseline, 1, 2, 3 and 6 months after treatment commencement
Secondary outcome [4] 416458 0
Discomfort symptoms on the Symptom Analysis in Dry Eye visual analogue scale (SANDE)
Timepoint [4] 416458 0
Baseline, 1, 2, 3 and 6 months after treatment commencement
Secondary outcome [5] 416459 0
Meibomian gland expressibility grade evaluated with the Meibomian Gland Evaluator (MGE)
Timepoint [5] 416459 0
Baseline, 1, 2, 3 and 6 months after treatment commencement
Secondary outcome [6] 416460 0
Lid wiper epitheliopathy (LWE) assessed with lissamine green vital dye and slit lamp biomicroscopy
Timepoint [6] 416460 0
Baseline, 1, 2, 3 and 6 months after treatment commencement
Secondary outcome [7] 416461 0
Bulbar hyperaemia as assessed objectively with the Oculus Keratograph 5M
Timepoint [7] 416461 0
Baseline, 1, 2, 3 and 6 months after treatment commencement

Eligibility
Key inclusion criteria
Age greater or equal to 18 years, able and willing to comply with study instructions
• Minimum of 6 months since onset of self-reported Dry Eye Disease (DED) symptoms
• Normal lid architecture, and closure
• Dry eye diagnosis according to the Tear Film and Ocular Surface Dry Eye Workshop II (TFOS DEWS II) diagnostic criteria (Symptoms: Dry Eye Questionnaire 5 (DEQ5( greater or equal to 6 or Ocular Surface Disease Index (OSDI) greater or equal to 13 and Signs: 1 positive finding on Non Invasive Break Up Time (NIBUT) (<10 s) / osmolarity (308mOsm/L or interocular difference of > 8mOsm/L) /staining (> 5 corneal spots, 9 conjunctival spots or Lid Wiper Epitheliopathy (LWE) of 2mm length and 25% lid margin width)
• Evidence of blepharitis (lash crusting (>10 lashes), madarosis (>20% missing lashes), lipid layer grade greater or equal to 2, meibomian gland capping grade greater or equal to 1, and/or meibomian gland expressibility score of greater or equal to grade 2)
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
• Abnormal eyelid architecture that prevents full eyelid closure during blinking
• Inability or unwillingness to commit to 6-month trial
• Unwillingness or inability to refrain from topical eye drop use, including artificial tear supplements, for at least 48 hours prior to baseline visit or within 24 hours of any subsequent study visit
• Refusal to limit topical supplement use to ‘rescue use’ only
• Refusal to be advised of incidental findings
• Wear of contact lenses within 48 hours of study commencement or during the study
• Warm compress therapy within 30 days of screening unless applied regularly and consistently throughout the course of the study and not within 48 hours of the screening visit or within 24 hours of subsequent clinical visits.
• Lid debridement or therapeutic gland expression within 30 days of the screening visit or during the course of the study
• Prior iLux, Lipiflow or IPL treatment within 6 months of study commencement
• Punctal plugs, unless non-dissolvable (silicone plugs or cautery of < 3 months duration)
• History of ocular surgery (such as refractive or cataract surgery) in either eye within 3 months of the screening visit
• History or presence of any ocular disorder or condition in either eye that would likely interfere with the interpretation of the study results or patient safety. This includes but is not limited to significantly reduced visual acuity (>20/200), significant corneal or conjunctival scarring, pterygium or nodular pinguecula; current ocular infection or inflammation unrelated to dry eye; anterior (epithelial) basement membrane corneal dystrophy or other clinically significant corneal dystrophy or degeneration; ocular herpetic infection
• Use of topical medications that might interfere with the study outcomes, or deemed to be
contraindicated for participation
• A systemic condition or disease considered unstable or judged by the investigator to be
incompatible with participation in the study (including but not limited to current systemic infection, uncontrolled autoimmune disease, uncontrolled immunodeficiency disease)
• Self-reported pregnancy or lactation.
• Active or uncontrolled severe systemic allergy, chronic seasonal allergies, rhinitis or sinusitis requiring treatment (with antihistamines, decongestants, oral or aerosol steroids) at the time of screening visit or during the trial
• Current or planned use of medication known to cause ocular drying (including but not limited to antihistamines, tricyclic antidepressants, anxiolytics, antimuscarinics, beta-blocking agents, diuretics, phenothiazines, steroids) within 30 days of the screening visit
• Use of oral medications not associated with ocular drying, unless stable dose for at least 30 days and continued at the same dose throughout the trial
• Participation in any clinical trial with a new active substance or a new device within 30 days of the screening visit

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)
Eligible participants who meet the inclusion criteria will be randomised to one of the two treatment groups (castor oil or saline). Castor oil and saline bottles will be labelled according to a pre-determined randomisation schedule by a third party prior to study start and issued to participants in an opaque envelope. The investigator involved in baseline participant assessment will have no influence in treatment allocation.
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 assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Prospective, randomised, double-masked, parallel group, 6-month efficacy trial comparing a proprietary cold-pressed castor oil preparation to a placebo control (saline).
Phase
Not Applicable
Type of endpoint/s
Efficacy
Statistical methods / analysis
A minimum of 84 completed participants (at the 3-month time point) will form the study group. It is anticipated that 92 participants will be recruited in order to obtain the necessary sample size by 3 months, allowing for ~10% drop out. Due to the nature of the study, it is acknowledged that drop out beyond 3 months may occur if symptomatic resolution is not achieved. Statistics performed and data interpretation beyond this time will be adjusted accordingly at the 6-month time point.

Justification: Sample size requirements were determined from non--parametric adjusted power calculations conducted using PASS 2002 (NCSS, Kaysville, UT), with anterior blepharitis grading (lash crusting grade) and noninvasive tear film breakup time as designated co-primary outcome measures. Power calculations using non-invasive tear film breakup time demonstrated a greater sample size requirement of 84 participants, with a minimum of 42 participants per treatment group, to allow for detection of a clinically significant difference of 4 seconds, with 80% power (ß = 0.2), at a two-sided statistical significance level of 5% (a = 0.05), and an estimated standard deviation of 6 seconds.

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
16/01/2023
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
92
Accrual to date
Final
Recruitment outside Australia
Country [1] 25150 0
New Zealand
State/province [1] 25150 0
Auckland

Funding & Sponsors
Funding source category [1] 312698 0
Commercial sector/Industry
Name [1] 312698 0
TRG Natural Pharmaceuticals
Country [1] 312698 0
New Zealand
Primary sponsor type
University
Name
The University of Auckland
Address
85 Park Road, Grafton, Auckland 1023
Country
New Zealand
Secondary sponsor category [1] 314314 0
None
Name [1] 314314 0
none
Address [1] 314314 0
none
Country [1] 314314 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 311998 0
The University of Auckland Human Participants Ethics Committee (UAHPEC)
Ethics committee address [1] 311998 0
85 Park Road, Auckland, New Zealand 1023
Ethics committee country [1] 311998 0
New Zealand
Date submitted for ethics approval [1] 311998 0
Approval date [1] 311998 0
16/03/2018
Ethics approval number [1] 311998 0
020783

Summary
Brief summary
Blepharitis is considered an entry point into the vicious circle of dry eye disease, a self-perpetuating cycle of instability, hyperosmolarity, inflammation and ocular surface damage, and its pathophysiology can be represented as an inner vicious circle which promotes tear film instability and feeds into the dry eye disease vicious circle.
This prospective, 6-month, double-masked, randomised, parallel group comparator trial aims to contribute sound scientific evidence to help address a current gap in the existing dry eye disease literature, especially with regard to:
(1) The maximal benefit that can be achieved from twice daily periocular application of castor oil relative to baseline
(2) The relative efficacy and patient reported experience of twice daily castor oil formulation
application compared to twice daily application of saline (placebo control)
(3) The temporal profile or clinical course of benefit arising from ongoing application, including the time taken to reach maximal benefit, based on clinically meaningful improvements in dry eye symptoms and signs.
The overall aim is to assist practitioners in recognising the potential benefits of a natural castor oil-based formulation for the management of blepharitis, to be able to set realistic expectations regarding magnitude of effect according to presenting severity, and to provide sound evidence regarding efficacy and patient satisfaction relative to a placebo control.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 123118 0
Prof Jennifer P. Craig
Address 123118 0
Department of Ophthalmology, The University of Auckland Private Bag 92019, Auckland, 1142
Country 123118 0
New Zealand
Phone 123118 0
+6499238173
Fax 123118 0
Email 123118 0
jp.craig@auckland.ac.nz
Contact person for public queries
Name 123119 0
Prof Jennifer P. Craig
Address 123119 0
Department of Ophthalmology, The University of Auckland Private Bag 92019, Auckland, 1142
Country 123119 0
New Zealand
Phone 123119 0
+6499238173
Fax 123119 0
Email 123119 0
jp.craig@auckland.ac.nz
Contact person for scientific queries
Name 123120 0
Prof Jennifer P. Craig
Address 123120 0
Department of Ophthalmology, The University of Auckland Private Bag 92019, Auckland, 1142
Country 123120 0
New Zealand
Phone 123120 0
+6499238173
Fax 123120 0
Email 123120 0
jp.craig@auckland.ac.nz

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.