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

Assiut University

Status and phase: Unknown; Phase 4

Conditions: Vitiligo

Treatments: Drug: Methotrexate; Device: Fractional CO2 laser; Drug: 5-fluorouracil

Study type: Interventional

Funder types: Other

Identifiers

NCT05008887

MTXVITILIGO

Details and patient eligibility

About

Vitiligo is a common acquired, depigmenting skin disease that affect the patient's psychological state and quality of life.

Full 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.

Enrollment: 50 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

1. History of skin cancers, keloid, hypertrophic scars or photosensitivity.
2. Use of any topical medications, phototherapy, or laser for vitiligo within 1 month prior to enrollment.
3. Renal, hepatic, hematological or debilitating chronic diseases.
4. Active inflammation or infection at site of treatment.
5. Pregnant and lactating females.
6. Age under 18 years old.
7. Segmental vitiligo, active or extensive disease.
8. Unrealistic expectation.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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50 participants in 2 patient groups

Fractional CO2 laser and topical methotrexate solution

Experimental group

Description:

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.

Treatment:

Drug: Methotrexate

Device: Fractional CO2 laser

Fractional CO2 laser and topical 5-fluorouracil solution

Active Comparator group

Description:

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.

Treatment:

Device: Fractional CO2 laser

Drug: 5-fluorouracil