Aqueous Tear Deficiency, Meibomian Gland Dysfunction of Bilateral Eyes (Disorder)
Conditions
Keywords
testosterone, fluorescein breakup time, androgen, dry eye
Brief summary
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
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.
Interventions
DRUGTestosterone gel 4.5%
Testosterone gel applied to eyelids twice per day
DRUGVehicle gel
Vehicle gel applied to eyelids twice per day
Sponsors
Southern California College of Optometry at Marshall B. Ketchum University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Masking description
Double
Intervention model description
Subjects randomized to either placebo or drug
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Tear Break up Time | From baseline to 4 weeks treatment | Time to first dark spot appearance in the tear film |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Lower Meibomian Gland Secretion Score (0 - 32 Scale) | From baseline to 4 weeks treatment | 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Vehicle Gel Vehicle gel applied to eyelids twice per day
Vehicle gel: Vehicle gel applied to eyelids twice per day | 12 |
| Testosterone Gel 4.5% Testosterone gel 4.5% applied to eyelids twice per day
Testosterone gel 4.5%: Testosterone gel applied to eyelids twice per day | 12 |
| Total | 24 |
Baseline characteristics
| Characteristic | Vehicle Gel | Testosterone Gel 4.5% | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 2 Participants | 2 Participants | 4 Participants |
| Age, Categorical Between 18 and 65 years | 10 Participants | 10 Participants | 20 Participants |
| Age, Continuous | 51.0 years STANDARD_DEVIATION 14.6 | 52.9 years STANDARD_DEVIATION 11.3 | 52.0 years STANDARD_DEVIATION 12.8 |
| Fluorescein tear breakup time | 3.3 seconds STANDARD_DEVIATION 0.9 | 3.6 seconds STANDARD_DEVIATION 1.2 | 3.5 seconds STANDARD_DEVIATION 1.1 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 6 Participants | 3 Participants | 9 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 6 Participants | 9 Participants | 15 Participants |
| Region of Enrollment United States | 12 participants | 12 participants | 24 participants |
| Sex: Female, Male Female | 9 Participants | 9 Participants | 18 Participants |
| Sex: Female, Male Male | 3 Participants | 3 Participants | 6 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 12 | 0 / 12 |
| other Total, other adverse events | 0 / 12 | 0 / 12 |
| serious Total, serious adverse events | 0 / 12 | 0 / 12 |
Outcome results
Primary
Tear Break up Time
Time to first dark spot appearance in the tear film
Time frame: From baseline to 4 weeks treatment
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Vehicle Gel | Tear Break up Time | 0.0 seconds | Standard Deviation 1.2 |
| Testosterone Gel 4.5% | Tear Break up Time | 2.9 seconds | Standard Deviation 1.3 |
Secondary
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.
Time frame: From baseline to 4 weeks treatment
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Vehicle Gel | Lower Meibomian Gland Secretion Score (0 - 32 Scale) | 0.7 units on a scale | Standard Deviation 0.3 |
| Testosterone Gel 4.5% | Lower Meibomian Gland Secretion Score (0 - 32 Scale) | 5.5 units on a scale | Standard Deviation 2.1 |