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Trial registered on ANZCTR


Registration number
ACTRN12622000273785p
Ethics application status
Submitted, not yet approved
Date submitted
7/01/2022
Date registered
14/02/2022
Date last updated
14/02/2022
Date data sharing statement initially provided
14/02/2022
Type of registration
Prospectively registered

Titles & IDs
Public title
Does treating dry eye improve outcomes for migraine sufferers?
Scientific title
Does treating dry eye improve outcomes for migraine sufferers?
Secondary ID [1] 306147 0
Nil known
Universal Trial Number (UTN)
U1111-1273-1059
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Migraine 324846 0
Dry eye disease 324847 0
Condition category
Condition code
Neurological 322286 322286 0 0
Other neurological disorders
Eye 322287 322287 0 0
Diseases / disorders of the eye

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
This study is a prospective, randomized, double-masked, cross-over, placebo-controlled, clinical trial in which patients with migraine AND an dry eye questionnaire OSDI score of >13 or a DEQ-5 score of >6 will be invited to participate. Participants will attend three visits. Participants will receive 4 weeks of Systane Hydration and 4 weeks of comparator, separated by a 2-week washout period. Each eye drop will need to be instilled by the participant 4 times a day (one drop per eye each time). Both Systane Hydration and saline are available over-the-counter. Compliance will be monitored with a diary and with the return of the eye drops.
Intervention code [1] 322555 0
Treatment: Other
Comparator / control treatment
The control treatment is with 0.9% saline eye drops which are available over-the-counter.
Control group
Placebo

Outcomes
Primary outcome [1] 330046 0
Ocular Surface Disease Index questionnaire (OSDI)
Timepoint [1] 330046 0
Visit 1: Baseline
Visit 2: 4 weeks after treatment 1 initiation
Visit 3: 4 weeks after treatment 2 initiation

Secondary outcome [1] 404711 0
migraine frequency and severity as measured with a validated questionnaire: The Migraine Disability Assessment Test and, the headache impact test
Timepoint [1] 404711 0
Visit 1: Baseline
Visit 2: 4 weeks after treatment 1 initiation
Visit 3: 4 weeks after treatment 2 initiation
Secondary outcome [2] 404712 0
Non-invasive tear break-up time which is measured at each visit using the Oculus Keratograph, an instrument which observes the stability of the tear film non-invasively and objectively.
Timepoint [2] 404712 0
Visit 1: Baseline
Visit 2: 4 weeks after treatment 1 initiation
Visit 3: 4 weeks after treatment 2 initiation
Secondary outcome [3] 404713 0
tear film calcitonin gene-reactive peptide (CGRP) levels
Timepoint [3] 404713 0
Visit 1: Baseline
Visit 2: 4 weeks after treatment 1 initiation
Visit 3: 4 weeks after treatment 2 initiation

Eligibility
Key inclusion criteria
• Patients with either episodic or chronic migraine. Episodic migraine: < 15 headache days per month for > 3 months; Chronic Migraine (> or equal to 15 headache days per month for > 3 months, where > or equal to 8 are migraine)
• Patients with dry eye disease: OSDI > 12 OR DEQ-5 >6 AND at least one of the following signs: Non-invasive keratography break-up time (NIKBUT) < 10, the presence of corneal or conjunctival staining, or osmolarity values > 308 mOsm/L or > 8mOsm/L difference between eyes
• All prescription meds for headache have been used consistently for at least 2 months prior to the study.
A condition of study participation is that patients do not change their systemic medication regime for the study duration. They will be asked to cease ocular lubricant use at Visit 1, and to return to that for the two-week washout period only.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
• Previous refractive surgery
• Previous corneal ulceration or ocular infection with Herpes Viruses
• Current or previous history of B12 deficiency
• Diabetes
• Multiple Sclerosis
• Chemotherapy
• Exclude those on daily topical eye drops
• Contact lens wear

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)
The participant will be randomized at the initial study visit, after they have provided informed consent and once it is clear that they have met the study criteria for phase 2. At this visit the participant will be randomized to the initial arm of the study (intervention or comparator) and will receive a Randomization Number, allocated by an independent statistician (A/Professor Thomas John).
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
The Randomization Number will be allocated by an independent statistician (A/Professor Thomas John) and this will be entered into RedCap so that the randomisation is allocated on enrolment.
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
Crossover
Other design features
Phase
Not Applicable
Type of endpoint/s
Efficacy
Statistical methods / analysis
Statistical analysis will be performed by an independent statistician, A/Professor Thomas John, Brien Holden Vision Institute. Primary analysis will be undertaken using ANCOVA with factors of visits (Visit 1, 2 and 3) and treatment group (Systane Hydration, Saline). Regression analysis will be used to investigate the relationship between dry eye parameters, migraine severity and comfort scores. Multivariate analysis techniques will be used to assess CGRP levels to predict dry eye disease and migraine severity. Assumptions of normal distribution and constant variance will be verified for all the above analyses. If necessary, data transformation will be used.
Pearson’s correlation coefficient/Point-Biserial correlation coefficient (r) or and Spearman’s rank correlation (rs) correlations will be performed to assess the relationship between migraine severity and CGRP, corneal nerve parameters and ocular comfort. General linear regression modelling will be used to examine the effect of the independent variables (migraine severity status, age, gender) on comfort, dry eye parameters, measures of inflammation, tear film CGRP, and corneal nerve parameters.
Reasons and frequency distribution of subjects discontinued will be reported. The analysis of efficacy variables such as subjective ratings will employ only scheduled and evaluable visits. The analysis of safety variables such as adverse responses will include all visits, including all unscheduled visits.

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
28/02/2022
Actual
Date of last participant enrolment
Anticipated
31/05/2022
Actual
Date of last data collection
Anticipated
31/08/2022
Actual
Sample size
Target
30
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 21446 0
Prince of Wales Hospital - Randwick
Recruitment postcode(s) [1] 36346 0
2031 - Randwick

Funding & Sponsors
Funding source category [1] 310489 0
Commercial sector/Industry
Name [1] 310489 0
Alcon Ltd
Country [1] 310489 0
Australia
Primary sponsor type
University
Name
University of New South Wales
Address
UNSW School of Optometry and Vision Science, Rupert Myers Building, Barker St, Kensington NSW 2033
Country
Australia
Secondary sponsor category [1] 311654 0
None
Name [1] 311654 0
Address [1] 311654 0
Country [1] 311654 0

Ethics approval
Ethics application status
Submitted, not yet approved
Ethics committee name [1] 310118 0
South Eastern Sydney Local Health District District HREC
Ethics committee address [1] 310118 0
Ethics committee country [1] 310118 0
Australia
Date submitted for ethics approval [1] 310118 0
28/01/2022
Approval date [1] 310118 0
Ethics approval number [1] 310118 0

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 116538 0
Prof Arun Krishnan
Address 116538 0
High St
Nerve and Muscle Clinic
Neurology Department
Prince of Wales Hospital
NSW 2031
Country 116538 0
Australia
Phone 116538 0
+6129382 2414
Fax 116538 0
+6129382 2428
Email 116538 0
arun.krishnan@unsw.edu.au
Contact person for public queries
Name 116539 0
Maria Markoulli
Address 116539 0
School of Optometry and Vision Science
Gate 14, Barker St
North Wing, Rupert Myers Building
UNSW 2052
Country 116539 0
Australia
Phone 116539 0
+61290657355
Fax 116539 0
Email 116539 0
m.markoulli@unsw.edu.au
Contact person for scientific queries
Name 116540 0
Maria Markoulli
Address 116540 0
School of Optometry and Vision Science
Gate 14, Barker St
North Wing, Rupert Myers Building
UNSW 2052
Country 116540 0
Australia
Phone 116540 0
+61290657355
Fax 116540 0
Email 116540 0
m.markoulli@unsw.edu.au

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
Participant data are considered confidential and will not be available.


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.