The Value of Methotrexate in NCES for Stable Vitiligo

March 3, 2026 updated by: Nanis Aleem Abdul Moneim Ragab, Cairo University

The Value of Using Methotrexate Therapy Along With Non Cultured Epidermal Cell Suspension (NCES) in Stable Resistant Vitiligo: An Interventional Prospective Randomized Controlled Trial.

The goal of this clinical trial is to learn if adding a six months course of Methotrexate would improve the results of non cultured epidermal suspension (NCES) in adult patients with acral and resistant vitiligo lesions over the elbows and knees. researchers will compare results of NCES in two groups one group will receive Methotrexate for 3 months prior to the procedure and 3 months after the procedure, while the other group will not receive the drug. Patients will receive PUVA hand & feet 3 times/week for 3 months after NCES during this period they will be followed up monthly to evaluate repigmentation.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

Depending on the type, extent, and duration of vitiligo, conventional medical therapies such as topical and systemic corticosteroids, topical immunomodulators, and phototherapy are not always successful, and repigmentation is often incomplete. Acral vitiligo as well as vitiligo over friction sites as elbows and knees are resistant to treatment including surgical procedures. Relatively less melanocyte density as well as higher chances of koebnerization over these friction and injury prone anatomical sites were among the suggestions for poor response to treatment. It was also found that melanocyte growth and migration in acral vitiligo is hindered by several factors such as decreased MMP9, MMP2, c-kit and MHCII expression, together with higher expression of antimelanogenic factors as tenascin and DKK1. Non-cultured epidermal cellular suspension (NCES) is a cellular grafting technique, whose major advantage is permitting treatment of affected skin surface area up to 10 times larger than the donor area without culturing. Methotrexate is an antifolate drug, that decreases the number of T cells. Studies showed that methotrexate has a positive effect on the stabilization of vitiligo. Combined treatment with phototherapy allows better and faster repigmentation than phototherapy alone. Systemic drugs have been previously used perioperatively in vitiligo surgery. Oral betamethasone has been previously used in the peri surgical period and was reported to increase the chances of complete repigmentation in large vitiliginous lesions as activity at the cellular level is still plausible in spite of clinical stability. The aim of this study is to assess whether adding methotrexate therapy to NCES in the peri surgical period would improve repigmentation in acral vitiligo and other resistant sites.

  • Inclusion criteria:

    • Patients with non-segmental vitiligo (NSV) with acral or resistant lesions over the elbows and knees, that has not responded to conventional treatment
    • Stability for ≥ 1 year
    • Age ≥18 years
    • Lack of topical treatment for at least 1 month prior to surgery and systemic treatment for at least 3 months prior to surgery.

  • Exclusion criteria:

    • Non acral NSV responsive to conventional treatment modalities
    • Active vitiligo; new lesions, expansion of old lesions, confetti like lesions, ill-defined edges or koebnerization in < 1 year
    • Age < 18 years.
    • Pregnant females.
    • Patients with hematologic, hepatic, renal disease or chronic infection.
    • Topical treatment in the past month and systemic treatment in the past 3 months.
  • Methodology in details:
  • forty lesions in patients with stable vitiligo will be recruited (20 size and region matched lesions per group). An informed written consent will be obtained from patients.
  • Patients will be randomized using a computer generated list to one of the two groups which are age and sex matched:

Group A will undergo None cultured epidermal suspension (NCES) without methotrexate.

Group B will receive methotrexate 15 mg/week for 3 months prior to NCES and for 3 months afterwards.

Clinical assessment:

Baseline assessment will include assessing any pigmentation within the patch to be transplanted using the VESTA score and its surface area using point counting technique.

Standardized photographs will be taken at initial assessment, and by the end of the study period after 3 months.

Under aseptic precautions and local anesthesia, a Thiersch graft about one-third the size of the recipient area will be harvested from the donor site (usually upper thigh/ buttocks). The skin graft will be transferred to trypsin-EDTA solution and incubated at 37 °C for 20-30 minutes to separate epidermis from the dermis and then washed with PBS. The tissue will be teased gently with sterile forceps to release epidermal cells from the trypsin digested graft. The white dermis will be removed, and the suspension will be centrifuged at 1000g for 5-10 minutes and the supernatant will be discarded.

Under strict asepsis, the recipient vitiliginous areas will be anesthetized followed by fractional laser CO2 resurfacing, using dot mode off resurfacing at a power of 18-20 W, dwell time 1,500-2000 milliseconds (DEKA, Florence, Italy). One to three passes will be performed until the epidermis is removed uniformly. Then, the NCES will be applied and uniformly spread. It will be covered with a dry collagen sheet followed by sterile surgical pad and tegaderm.

The area will be immobilized after bandaging and the patient will be advised to restrict movement at the operated site.

Patients will start a 1-week course of antibiotics. Dressings will be removed after 1 week, and patients will start topical PUVA hand and feet, 3 times per week for 3 months.

Patients will be followed up monthly for 3 months following the first visit at 1 week.

Both qualitative and quantitative assessment will be done after 3 months of PUVA Hand and feet. Qualitatively, blinded physician assessment of repigmentation as well as color match will be done based on baseline photographs. Quantitatively, point counting method as well as VESTA score will be used as well to assess the surface area of the residual depigmented area and degree of repigmentation respectively.

Study Type

Interventional

Enrollment (Estimated)

20

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • Egypt
      • Cairo, Egypt
        • Recruiting
        • Dermatology Outpatient Clinic, Kasr al Ainy Teaching Hospital, Cairo University
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

  • Inclusion criteria:

    • Patients with non-segmental vitiligo (NSV) with acral or resistant lesions over the elbows and knees, that has not responded to conventional treatment
    • Stability for ≥ 1 year
    • Age ≥18 years

  • Exclusion criteria:

    • Segmental vitiligo
    • Active vitiligo; new lesions, expansion of old lesions, confetti like lesions, ill-defined edges or koebnerization in < 1 year
    • Age < 18 years.
    • Pregnant females.
    • Patients with hematologic, hepatic, renal disease or chronic infection.
    • Topical treatment in the past month and systemic treatment in the past 3 months.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: NCES
Procedure: Non cultured epidermal suspension

Under aseptic precautions and local anesthesia, a Thiersch graft about one-third the size of the recipient area will be harvested from the donor site (usually upper thigh/ buttocks). The skin graft will be transferred to trypsin-EDTA solution and incubated at 37 °C for 20-30 minutes to separate epidermis from the dermis and then washed with PBS. The tissue will be teased gently with sterile forceps to release epidermal cells from the trypsin digested graft. The white dermis will be removed, and the suspension will be centrifuged at 1000g for 5-10 minutes and the supernatant will be discarded.

Under strict asepsis, the recipient vitiliginous areas will be anesthetized followed by fractional laser CO2 resurfacing, using dot mode off resurfacing at a power of 18-20 W, dwell time 1,500-2000 milliseconds (DEKA, Florence, Italy). One to three passes will be performed until the epidermis is removed uniformly. Then, the NCES will be applied and uniformly spread.
Experimental: NCES+Methotexate
Procedure: Non cultured epidermal suspension

Under aseptic precautions and local anesthesia, a Thiersch graft about one-third the size of the recipient area will be harvested from the donor site (usually upper thigh/ buttocks). The skin graft will be transferred to trypsin-EDTA solution and incubated at 37 °C for 20-30 minutes to separate epidermis from the dermis and then washed with PBS. The tissue will be teased gently with sterile forceps to release epidermal cells from the trypsin digested graft. The white dermis will be removed, and the suspension will be centrifuged at 1000g for 5-10 minutes and the supernatant will be discarded.

Under strict asepsis, the recipient vitiliginous areas will be anesthetized followed by fractional laser CO2 resurfacing, using dot mode off resurfacing at a power of 18-20 W, dwell time 1,500-2000 milliseconds (DEKA, Florence, Italy). One to three passes will be performed until the epidermis is removed uniformly. Then, the NCES will be applied and uniformly spread.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Percent change in surface area by point counting method after NCES alone versus NCES combined with MTX
Time Frame: 3 months
A decrease in the surface area (number of points) of depigmented area indicates successful regimentation
3 months
Percent change in surface area by VESTA score after NCES alone versus NCES combined with MTX
Time Frame: 3 months
VESTA score ranges between 0-100% (0 % is complete depigmentation and 100% is fully pigmented) an increase in VESTA score indicates successful regimentation
3 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Cairo University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

March 3, 2026

Primary Completion (Estimated)

September 1, 2026

Study Completion (Estimated)

September 1, 2026

Study Registration Dates

First Submitted

January 11, 2026

First Submitted That Met QC Criteria

January 11, 2026

First Posted (Actual)

January 20, 2026

Study Record Updates

Last Update Posted (Actual)

March 4, 2026

Last Update Submitted That Met QC Criteria

March 3, 2026

Last Verified

March 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • MTXNCES

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

I will share the deidentified data sheet of the results of the trial

IPD Sharing Time Frame

1 month after paper publication

IPD Sharing Supporting Information Type

  • STUDY_PROTOCOL
  • SAP

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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