Clinical trial NCT06392438: Cyclosporine and Intense Pulsed Light for Dry Eye in Contact Lens Users
Official title: Combination of 0.09% Cyclosporine and Intense Pulsed Light (IPL) Therapy for the Treatment of Dry Eye Disease in Symptomatic Contact Lens Wearers: a Sham-Controlled Randomized Clinical Trial
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Dry Eye
Contact Lens Complication
Keywords: Contact Lens Discomfort
Intense Pulsed Light
Cyclosporine
Lead sponsor: Université de Sherbrooke
Sponsor class: OTHER
First posted: 2024-04-30
Enrollment: 44
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: This study is a randomized, sham controlled clinical trial. It consists of two treatments, one of which is applied to all the participants (cyclosporine). and the second one, for which participants are randomized in either the IPL group (experimental) or the IPL-sham group (control). Data collection is a pre-post model, with data being collected at baseline, during the trial (mid-study) and after the treatments. Data analysis is in intent-to-treat.
Primary purpose: TREATMENT

Brief summary: In this study, two treatments typically used for dry eye disease will be tried for contact lens users to see if their symptoms when they use their contact lenses get better. Cyclosporine is a drop that is used for long-term management of the inflammation and Intense pulsed light (IPL) is a treatment done in a clinic to improve the health of the eyelid glands. The main question in this study is:

Does the combined treatment of cyclosporine and IPL improve the symptoms and the dry eye signs of contact lens wearers?

All the participants will receive the cyclosporine drops for 4 months twice a day. The research team will split the group of participants in two, half receiving the real IPL treatment and half receiving a sham IPL treatment during the last two months of the study. This will allow to compare the two groups to see how IPL helped. The dry eye tests will be done at the start of the study, after two months and after 4 months. The tests will include a dry eye symptoms questionnaire, measures on the tears, the structures of the front of the eye and the eyelids.

Detailed description: Dry eye disease is a complex and multifactorial pathology in which inflammation and changes to the tear film (instability and hyperosmolarity) play important roles. Dry eye disease is very common, with an estimated global prevalence of 11.59% although other analyses conclude to 50% of some populations suffering from dry eye. The condition has been traditionally classified in two subtypes: aqueous tear deficiency (secondary to a deficit of production by the lacrimal gland) and evaporative disease (secondary to a deficit of the lipid layer of the tear film), but when the condition progresses, almost all patients present characteristics of both subtypes. Meibomian gland dysfunction (MGD) is one of the conditions that is most frequently associated with dry eye disease and leads to evaporative dry eye and alterations of the ocular surface. The prevalence of MGD has been recently established between 21.2% and 29.5% in subjects of African and Caucasian race and higher among Arabs, Hispanics, and Asians. Many risk factors exist for dry eye disease and MGD, including age and usage of contact lens. Soft contact lenses (SCL) are used by hundreds of millions for visual correction. The wear of SCL, however, has the potential to create or worsen dry eye signs and symptoms. A comparative study has found that 39% of North-American wearers can be categorized as symptomatic of contact lens dry eye and the proportion of uncomfortable users increases with age. SCL wear can increase evaporative dry eye by weakening the lipid layer, which leads to decreased stability of the tear film and increased evaporation. It also contributes to aqueous dry eye etiology by reducing the tear volume. The wear of SCL has also been shown to have a damaging effect on meibomian glands and, in some cases, on the conjunctival goblet cells .

Arguments also support the role of SCL in the inflammation of the ocular surface, even in asymptomatic patients. Thus, dry eye disease associated with SCL wear is a complex condition that implies different mechanisms.

Cyclosporine A is a peptide produced by a fungus that has been used systemically for decades for its potent immunomodulatory effects. Usage for dry eye disease in a topical 0.05% oil-based formulation has been common since the early 2000s. On the ocular surface, cyclosporine acts by inhibiting calcineurin, which subsequently blocks the activation of T cells and prevents the release of cytokines, therefore reducing inflammation. It has been shown to increase tear volume, goblet cell density and to reduce surface staining as well as symptoms in dry eye patients. Divergent results have been observed on contact lens wearers, although one study has found an amplified effect on contact lens wearers symptomatic of dry eye when combining essential fatty acid supplements with topical cyclosporine. Despite having been shown useful in the management of dry eye disease, the oil-based formulation is considered having a low bioavailability. A new cyclosporine eyedrop has been approved in Canada and the USA in the recent past years and is based on nanomicelle technology with a concentration of 0.09%. This nano-micellar formulation could be more effective in delivering the cyclosporine to the tissues and have been shown to reduce ocular surface staining, to increase tear volume, and to be safe. Adverse events that are known to this product are mild, such as transient pain at instillation for about 23% of patients.

Intense pulsed light (IPL) is a therapeutic process that has been used for many years in dermatology and esthetics. The noncoherent pulses of light produce photo-biochemical effects and, in the treatment of dry eye disease, the application on the skin around the orbit to produces these effects on the meibomian glands and their surrounding tissue. The mechanisms by which IPL improves signs and symptoms of dry eye are not fully understood, but the melting of the meibum, the clogging of telangiectatic inflammatory vessels, the reduction of epithelial turnover, the improvement in the collagen synthesis, a mitochondrial activity enhancement (photo modulation), and the destruction of parasitic and bacterial species are the main theoretical explanations. IPL has been shown to be an effective therapeutic option to manage MGD.

Dozens of studies have shown that IPL reduces dry eye symptoms, increases tear break-up time, improves the secreting function of the glands as well as the quality of the meibum and reduces corneal staining. IPL is often combined with meibomian gland expression to maximize the therapeutic effects; however, controlled studies have shown that IPL is largely responsible of these effects and that it is the core mechanism of this combination. Two studies have observed the effect of IPL on SCL users, with the conclusion that it is an effective treatment for this population. IPL is considered to be a safe treatment.

Since SCL have been linked to both aqueous and evaporative etiologies or dry eye, this research project aims to study the effect of combining these two treatments to target the entirety of the tear film, believed to be essential to comfortable SCL wear. This study will be a randomized clinical trial that contains two interventions: the 0.09% cyclosporine eyedrops (Cequa) and IPL treatment. The main objective of this study is to establish if the treatment of contact lens related dry eyes by the combination of 0.09% cyclosporine for 16 weeks and a standard IPL treatment (3 sessions) is more effective in relieving dry eye symptoms when compared to 0.09% cyclosporine for 16 weeks with a sham IPL treatment (3 sessions). The secondary objectives are to compare the effects of each treatment combination (0.09% cyclosporine+IPL vs 0.09% cyclosporine+sham) on signs of dry eye, to explore the effects of cyclosporine 0.09% drops alone on contact lens wearers and to assess the security profile of these interventions on SCL wearers.

Based on prior data from the f-CLDEQ-8 validation study, a major study on the cyclosporine nanomicelle formulation and the first clinical trial on IPL for contact lens wearers, a sample size of 44 participants (22/group) was calculated to be necessary to detect a significant difference between the groups. 44 participants will thus be recruited from a primary care optometric clinic and nearby clinics. Participation to the study will require 5 visits from the participants. The first visit will be a collection of data and the dispensing of the 0.09% cyclosporine drops. 8 weeks later, the participants will present for their 2nd visit, during which data will be collected once again and participants will be randomized to either the treatment or the sham group and will receive their first treatment (IPL or sham accordingly to the assignation). The 2 following visits, 3 weeks apart, will be for the 2 last IPL/sham treatments. A final visit will be for data collection 2 weeks after the last IPL/sham treatment. Participants will take 0.09% cyclosporine for the whole 16 weeks.

A bilateral t-test for independent samples will be used to compare the difference in change on the f-CLDEQ-8 between groups on the 16 weeks interval. Concerning the dry eye signs, statistical treatment will be made to account for inter-eye correlation. Continuous variables will be analyzed using a multi-level model to assess the difference in change between groups on the 16 weeks interval. Discrete variable will be analyzed using a general linear model (GLM) for the same comparison. Data will be handled in an intent-to-treat way.

Eligibility criteria: Inclusion Criteria:

* Soft silicone-hydrogel contact lens wearers
* Monthly, 2-weeks, opr daily replacement schedule of contact lens
* Minimum wear of contact lens for 1 day/week and 4 hours consecutive
* f-CLDEQ-8 score ≥ 12

Exclusion Criteria:

* Past usage of cyclosporine 0.09% (Cequa)
* Use of another ophthalmic cyclosporine drop in the past 6 months
* Known intolerance to cyclosporine
* Pregnancy or breastfeeding (or planned pregnancy in the duration study)
* History of ocular herpes simplex infection
* Active ocular infectious condition
* Usage of photosensitizing medication
* Epilepsy
* History of skin cancer in the IPL treatment zone
* Tattoo/pigmented lesion/keloid scars in the IPL treatment zone
* Refractive surgery in the past 12 months
* In-clinic thermal pulsation eyelid treatment in the past 12 months
* Usage of glaucoma drops
* Regular continuous wear of contact lenses (including sleep)
* Excessive movement or decentration of the contact lenses (assessed at first visit)
* Giant papillary conjunctivitis

Primary outcomes:
measure: Contact lens dry eye symptoms
timeFrame: Measured at each visit (Baseline, week 8, week 11, week 14 and week 16)
Secondary outcomes:
measure: Global rating scale of change
timeFrame: Tuesday and Saturday of every week for 16 consecutive weeks (while participating in the study)
measure: Average number of hours spent wearing contact lenses
timeFrame: Tuesday and Saturday of every week for 16 consecutive weeks (while participating in the study))
measure: Artificial tear usage while wearing contact lenses
timeFrame: Tuesday and Saturday of every week for 16 consecutive weeks (while participating in the study)
measure: Non-invasive tear break-up time over contact lenses (pre-lens tear film)
timeFrame: Baseline, week 8, and week 16
measure: Non-invasive tear break-up time (natural tear film)
timeFrame: Baseline, week 8, and week 16
measure: Tear break-up time
timeFrame: Baseline, week 8, and week 16
measure: Corneal staining score
timeFrame: Baseline, week 8, and week 16
measure: Conjunctival staining score
timeFrame: Baseline, week 8, and week 16
measure: Tear meniscus height (with contact lens in place)
timeFrame: Baseline, week 8, and week 16
measure: Tear osmolarity (with contact lens in place)
timeFrame: Baseline, week 8, and week 16
measure: Meibomian gland atrophy
timeFrame: Baseline and week 16
measure: Adverse effects
timeFrame: Week 8, week 11, week 14, and week 16
measure: Distance visual acuity
timeFrame: Measured at each visit (Baseline, week 8, week 11, week 14 and week 16)
measure: Intraocular pressure
timeFrame: Measured at each visit (Baseline, week 8, week 11, week 14 and week 16)
Other outcomes:
Locations:
city: Sherbrooke
country: Canada
facility: Opto-Réseau Sherbrooke Est
state: Quebec
Study officials:
affiliation: Professor University of Sherbrooke
name: Patrick Boissy, PhD
role: STUDY_CHAIR
affiliation: Professor University of Montreal
name: Langis Michaud, OD, MSc
role: STUDY_DIRECTOR
affiliation: PhD candidate University of Sherbrooke
name: Eric Lortie-Milner, OD
role: PRINCIPAL_INVESTIGATOR
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