Topical Cyclosporine Suspension for the Treatment of Brittle Nails

Study Overview
=================
Brief Summary
-----------------
Brittle nail syndrome (BNS) refers to nails that exhibit splitting, raggedness (fraying of the distal edge), and peeling (lamellar onychoschizia).(1) This is a common problem, affecting approximately 20% of women, with higher prevalence among the elderly.(2) A number of factors have been proposed as possible causes of nail brittleness, such as anemia, biotin deficiency, or cysteine deficiency. (3,4) However, most authors believe that brittle nails are usually caused by dehydration of the nail plate, either from repetitive cycles of hydration and dehydration related to hand washing or from exposure to dehydrating chemicals, such as those found in nail enamel and cuticle removers. (5,6) Inflammation of the nail as a potential contributing factor has never been studied. There are currently not consistently effective treatments for this condition. Restasis® is effective in treating keratoconjunctivitis sicca. This condition is characterized by the troublesome condition of dry eyes partially due to decreased tear production exacerbated by inflammation. The BNS manifests itself by nail plate dehydration. The two conditions have in common disruption of water balance which gives rise to problematic clinical disorders. The hypothesis is that a product which benefits tear production would also be effective for brittle nails which contain roughly 15% water.

Detailed Description
-----------------
Brittle nail syndrome (BNS) is a heterogeneous abnormality, characterized by increased fragility of the nail plate. About 20% of the population is affected by brittle nails and women are affected twice as frequently as men. (2). The diagnostic criteria for brittle nails are not well defined but most authors agree in at least these 3 criteria: onychoschizia (lamellar splitting of the free edge and distal portion of the nail plate), onychorrhexis (longitudinal thickening and thinning or ridging of the nail plate) and fraying or raggedness of the distal edge causing transverse splitting. Although the cause of nail brittleness is unknown, most authors believe that it is caused by dehydration of the nail plate and that frequent cycles of hydration and dehydration as well as various mechanical and chemical insults increase the incidence of brittle nails. (7) The nail plate contains about 15% water and a very low lipid content so water permeation through the nail plate is high.(8) In fact, it has been demonstrated that the flux of water across the nail plate is 10 times more than the epidermis and 1000 times more permeable than the stratum corneum.(9) A recent report show that there was no significant difference in water content of brittle nails when compared to normal nails and suggested that nail plate water content is random and that nail plates are in a constant state of influx and efflux of water. (10) Keratoconjunctivitis sicca is a chronic, bilateral desiccation of the conjunctiva and cornea due to an inadequate tear film. There are two types: one caused by an inadequate tear volume and the other one caused by an accelerated tear evaporation due to poor tear quality (11). Restasis® (cyclosporine 0.05% topical emulsion) is effective in treating keratoconjunctivitis sicca. BNS and keratoconjunctivitis sicca have in common a disruption of water balance which gives rise to problematic clinical disorders. We hypothesize that a product which improves corneal dehydration would also be effective for brittle nails. Our rationale for using occlusion is that is has been shown that occluding the skin with a vapor-permeable membrane increases the water flux and the barrier function is recovered at a normal rate. (12) We also hypothesize that using Restasis® (cyclosporine 0.05% topical emulsion) or its vehicle (Refresh Dry Eye Therapy®) under occlusion with a finger cot will increase the nail plate hydration balance and as a consequence will improve nail brittleness. Topical cyclosporine has been shown to be safe in the treatment of other dermatological conditions such as nail psoriasis and oral lichen planus. (13,14) An investigator-blinded design will differentiate if the observed effects are caused by the active ingredient in Restasis® (cyclosporine 0.05% topical emulsion) or its vehicle (Refresh Dry Eye Therapy®).

Official Title
-----------------
A Single Center, Investigator-blinded Study of the Efficacy of Topical Cyclosporine 0.05% Ophthalmic Suspension (RESTASIS®) Under Occlusion Versus Vehicle in the Treatment of Brittle Nail Syndrome

Conditions
-----------------
Brittle Nail Syndrome

Intervention / Treatment
-----------------
* Drug: topical cyclosporine ophthalmic suspension 0.05%
* Drug: vehicle


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: • Must understand and voluntarily sign an informed consent form Must be male or female and aged 18-75 years at time of consent Must be able to adhere to the study visit schedule and other protocol requirements At least 2 of the following: raggedness (fraying of the distal edge), splitting, and peeling (lamellar onychoschizia) of 2 target fingernails of the same hand. If the subject does not have 2 fingernails affected in the same hand, a second fingernail on the other hand may be used as control. A direct microscopic examination with potassium hydroxide (KOH)/calcofluor that is negative for hyphae associated with dermatophytes Women of childbearing potential must have a negative pregnancy test at enrollment Exclusion Criteria: Inability to provide voluntary consent Pregnant or breastfeeding Fingernail fungal infection Use of any investigational medication within 4 weeks prior to start of study drug Subject has any known immunodeficiency or history of malignancy in the last 4 years, excluding nonmelanoma skin cancer. Use of any topical nail medication for 2 weeks Use of any topical nail product (nail polish, hardeners, acetone, etc) for 1 week prior to and during the study. Use of biotin 2 weeks before enrollment. No genetic nail abnormalities Known sensitivity to Restasis® or RDET®. Subject has psoriasis, lichen planus, or other abnormalities that could result in a clinically abnormal fingernail

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: topical cyclosporine suspension<br>apply 2 drops to 2 target nails under occlusion daily for 20 weeks | Drug: topical cyclosporine ophthalmic suspension 0.05%<br>* apply 2 drops to 2 target fingernails under occlusion daily<br>* Other names: Restasis;|
| Placebo Comparator: vehicle<br>apply to target nails daily under occlusion daily for 20 weeks | Drug: vehicle<br>* apply 2 drops to 2 target fingernails under occlusion daily for 20 weeks<br>* Other names: Refresh Dry Eye Therapy;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| • Number of Patients Receiving at Least a 1-grade Improvement in the Physicians Global Improvement Assessment (PGIA) of Two Target Nails. | IN a scale of 0-3 where 0 means normal nail and 3 means severe disease, the number of patients who received at least a decrease of 1 grade in the evaluation of two target nails | 20 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Patients Assessment of Satisfaction With Length of Fingernails | the percentages of participants who were satisfied with the length of fingernails | 20 weeks | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
brittle nail