Eyelid Androgen Treatment in Dry Eye

Study Overview
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Brief Summary
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The purpose of this research study is to evaluate the effectiveness and safety of applying androgen sex hormone (i.e., testosterone) gel on the eyelids in the treatment of dry eye patients. Several studies have demonstrated positive treatment effects in dry eye, but few have applied testosterone gels to the eyelids.

Detailed Description
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The purpose of this study is to examine the safety and efficacy of transdermal eyelid application of testosterone gel along with the length of any beneficial effect following cessation of treatment. Moderate to severe dry eye subjects will be enrolled into a randomized controlled trial with assignment to either an   4.5% FDA-approved androgen gel (Natesto®, Acerus Pharmaceuticals, Mississagua, Canada) or a placebo formulated similar to Natesto® without testosterone. The gel will be applied to both eyelids in the morning and 12 hours later on both eyelids for a 30 day treatment period Subjects will fulfil DEWS II criteria for eligibility and further be classified as moderate or severe based on DEWS II recommendations. A standardized examination involving signs and symptoms of dry eye and monitoring function of the meibomian and lacrimal glands, as well as clinical tear and ocular surface measures, IOP, and serum testosterone levels, at baseline, following 30 days of testosterone application, and at one and two months post-treatment.

Official Title
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A Pilot Randomized Controlled Trial of Eyelid Androgen Treatment in Dry Eye

Conditions
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Aqueous Tear Deficiency, Meibomian Gland Dysfunction of Bilateral Eyes (Disorder)

Intervention / Treatment
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* Drug: Testosterone gel 4.5%
* Drug: Vehicle gel


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Moderate to severe dry eye (TBUT < 6.0 seconds, corneal staining > grade 1.5, evidence of meibomian gland secretion compromise or Schirmer < 5 mm wetting in 5 minutes) Age over 18 Mild ectropion Previous contact lens wearers IF no wear for prior 6 months Punctal plugs if more than three months since placement Systemic tetracyclines, antihistamines if consistent dosing Sjogren's syndrome and related autoimmune conditions can be enrolled Patients using topical dry eye treatments (e.g., Restasis) if willing to discontinue for 30 days Exclusion Criteria: If artificial tears or autologous serum used on day of study Ocular surgery if less than 12 months Punctal plugs if within 3 months of plug insertion Contact Lens wear within the six months prior to study PSA levels greater than 4 ng/ml or BPH Recent or current thrombolism Recent or current cardiovascular events (e.g., MI, stroke) Recent or current liver disorders Concurrent use of topical medications; e,g., topical glaucoma medications Diabetics Females of child-bearing age if not on reliable birth control History of breast cancer Cannot be taking insulin, warfarin or systemic corticosteroids

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Subjects randomized to either placebo or drug
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Vehicle Gel<br>Vehicle gel applied to eyelids twice per day | Drug: Vehicle gel<br>* Vehicle gel applied to eyelids twice per day<br>* Other names: placebo;|
| Active Comparator: Testosterone gel 4.5%<br>Testosterone gel 4.5% applied to eyelids twice per day | Drug: Testosterone gel 4.5%<br>* Testosterone gel applied to eyelids twice per day<br>* Other names: androgen gel 4.5%;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Fluorescein break up time (TBUT) | Time to first dark spot appearance in the tear film | From enrollment to two months post treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Lower meibomian gland secretion score (0 - 32 scale) | 8 central lower meibomian glands are evaluated using gentle (vs forceful) expression. Each secretion is given a score of 0 (clear normal meibum), 1 (cloudy low viscosity) 2 (thick, opaque, 3 inspissated or 4 (no secretion visible). One-half scale increments are used. | From enrollment to two months post treatment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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testosterone, fluorescein breakup time, androgen, dry eye