Fractional CO2 Laser-assisted Cutaneous Delivery of Methotrexate Versus 5-fluorouracil in Stable Non-segmental Vitiligo

Study Overview
=================
Brief Summary
-----------------
Vitiligo is a common acquired, depigmenting skin disease that affect the patient's psychological state and quality of life.

Detailed Description
-----------------
Vitiligo is a common acquired, depigmenting skin disease that affect the patient's psychological state and quality of life. Regarding treatment of vitiligo, several modalities are available but none are completely satisfactory. Recently, fractional carbon dioxide (CO2) laser has been introduced as an add-on treatment for vitiligo. Fractional CO2 laser acts by stimulating the release of cytokines and growth factors that act as mitogens for melanogenesis. Also, microscopic ablative zones produced by it promote the trans-epidermal penetration of topical agents, providing additional benefits for re-pigmentation. Recently topical methotrexate 1% gel was used in a case report of vitiligo and was applied to a single patch twice daily for 12 weeks with significant improvement in pigmentation without local or systemic side effects during the course of therapy. Thus, it may prove to be an important steroid sparing agent in treatment of vitiligo. As methotrexate is a large, hydrophilic molecule that does not penetrate intact skin, several drug delivery systems are being developed e.g. nano-vehicle preparations and laser-assisted delivery. One study has evaluated fractional Erbium laser-assisted delivery of topical methotrexate in porcine skin and found that methotrexate distribution and concentration in the mid-dermis was facilitated by ablative fractional laser, suggesting that ablative fractional laser-assisted topical methotrexate-delivery may be an appropriate alternative to systemic methotrexate for some skin disorders. Ablative fractional laser-assisted delivery of topical 5-fluorouracil has been used in vitiligo in several studies with good results. Serum interleukin-23 levels were significantly higher in vitiligo patients as compared with controls.

Official Title
-----------------
Efficacy of Fractional CO2 Laser-assisted Cutaneous Delivery of Methotrexate Versus 5-fluorouracil in Stable Non-segmental Vitiligo

Conditions
-----------------
Vitiligo

Intervention / Treatment
-----------------
* Drug: Methotrexate
* Drug: 5-fluorouracil
* Device: Fractional CO2 laser


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: The patients will be enrolled in the study if they have: Non-segmental vitiligo Stable disease (a patient reporting no new lesions, no progression of existing lesions, and absence of Koebner phenomenon during the past 1 year) Exclusion Criteria: History of skin cancers, keloid, hypertrophic scars or photosensitivity. Use of any topical medications, phototherapy, or laser for vitiligo within 1 month prior to enrollment. Renal, hepatic, hematological or debilitating chronic diseases. Active inflammation or infection at site of treatment. Pregnant and lactating females. Age under 18 years old. Segmental vitiligo, active or extensive disease. Unrealistic expectation.

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

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

Accepts Healthy Volunteers
-----------------
No

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

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Fractional CO2 laser and topical methotrexate solution<br>In all patients, the selected patches of vitiligo will be treated with fractional CO2 laser for 3 sessions at one-month intervals. In each patient, two patches or their duplicates (if small sized) will be subjected first to fractional CO2 laser treatment at two different energies (half the number of selected patches will be treated with 50 mJ-energy with the aim to use laser more as a delivery system to drug solution, and the other half will be treated with 100mJ-energy with the aim to use laser as both therapeutic and delivery system , followed by topical application of methotrexate solution (2.5% concentration vial 50mg/2ml using insulin syringe as 0.1 ml at 1 cm-intervals with a maximum volume of 2 ml per session). Then gentle massage will be done and after about 10 minutes, an occlusive dressing will be applied for 24 hours after the session. In all patients, the selected patches of vitiligo will be treated with fractional CO2 laser for 3 sessions at one-month intervals. | Drug: Methotrexate<br>* Fractional CO2 laser-assisted cutaneous delivery of methotrexate solution in stable, non-segmental vitiligo<br>Device: Fractional CO2 laser<br>* Fractional CO2 laser-assisted cutaneous delivery of methotrexate and 5-fluorouracil solution in stable, non-segmental vitiligo<br>|
| Active Comparator: Fractional CO2 laser and topical 5-fluorouracil solution<br>In all patients, the selected patches of vitiligo will be treated with fractional CO2 laser for 3 sessions at one-month intervals. In each patient, two patches or their duplicates (if small sized) will be subjected first to fractional CO2 laser treatment at two different energies (half the number of selected patches will be treated with 50 mJ-energy with the aim to use laser more as a delivery system to drug solution, and the other half will be treated with 100mJ-energy with the aim to use laser as both therapeutic and delivery system , followed by topical application of 5-fluorouracil solution 5% concentration vial 250mg/5ml using insulin syringe as 0.1 ml at 1 cm-intervals with a maximum volume of 2 ml per session). Then gentle massage will be done and after about 10 minutes, an occlusive dressing will be applied for 24 hours after the session. In all patients, the selected patches of vitiligo will be treated with fractional CO2 laser for 3 sessions at one-month intervals. | Drug: 5-fluorouracil<br>* Fractional CO2 laser-assisted cutaneous delivery of 5-fluorouracil solution in stable, non-segmental vitiligo<br>Device: Fractional CO2 laser<br>* Fractional CO2 laser-assisted cutaneous delivery of methotrexate and 5-fluorouracil solution in stable, non-segmental vitiligo<br>|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical evaluation | Photographic evaluation Patients will be evaluated by digital photographs at baseline, before each session and monthly for 3 months after the last session to evaluate the therapeutic response. Two non-treating blinded dermatologists will be asked to record percentage of improvement in the treated patches for each patient after completion of the treatment by comparing before and after digital photographs. The re-pigmentation response will be expressed qualitatively using a quartile grading scale (grade 0 = no improvement; 1, 1-25% = minimal; 2, 26-50% = moderate; 3, 51-75% = good; and 4, >75% = excellent). Quantitative assessment by the point counting technique: Quantitative assessment will be done by calculating the area of depigmentation in vitiliginous patches using a simple point counting method at baseline, before each session and at the final evaluation. The percentage reduction in lesion size will be then calculated. | 6 month (3 months of treatment and 3 months for follow up after last treatment) |