Clinical trial NCT02625012: Repigmentation Patterns Induced by NB-UVB and Their Relationship With Melanocytic Migration in Vitiligo
Official title: Repigmentation Patterns Induced by NB-UVB and Their Relationship With Melanocytic Dynamics in Vitiligo
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Vitiligo
Keywords: Ultraviolet Therapy
Vitiligo
Melanocytes
Pigmentation
Lead sponsor: Universidad Autonoma de San Luis Potosí
Sponsor class: OTHER
Collaborators: name: Hospital Central "Dr. Ignacio Morones Prieto"
First posted: 2015-12-09
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_ONLY
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients with clinical diagnosis of vitiligo vulgaris

Brief summary: Vitiligo is the most common acquired depigmented disorder of the skin characterized by destruction of melanocytes resulting in well-circumscribed achromic macules. Ultraviolet phototherapy with narrow band (UVB-NB) is currently one of the treatments of choice, because it is able to induce proliferation, differentiation, maturation and migration of melanocytes. This repigmentation has distinctive patterns such as follicular, marginal, and diffuse. The aim of this study is to observe the dynamics of migration and proliferation, in vitiligo patients under UVB radiation phototherapy treatment. The investigators will evaluate this process by measuring FAK (focal adhesion kinase ) and c-Kit by immunohistochemistry and reverse transcriptase polymerase chain reaction assay.

Detailed description: Vitiligo is the most common acquired depigmented disorder of the skin characterized by destruction of melanocytes, which results in well-circumscribed achromic macules. Its etiology is not fully recognized but functional melanocytes may disappear by autoimmune response, oxidative stress that induces melanocytes apoptosis, and loss of cell-cell adhesion between melanocytes and keratinocytes.

Ultraviolet phototherapy with narrow band (UVB-NB) is currently one of the treatments of choice with an average response rate of 60-70% on lesions. UVB-NB phototherapy may induce immune regulation and melanogenic induction. It is also able to induce Treg cells proliferation to suppress the autoimmune response which destroys melanocytes. By the other hand, UVB-NB induces signaling of proliferation, differentiation, maturation and migration of melanocytes, playing an important role in vitiligo re-pigmentation.

Phosphorylation of focal adhesion kinase (p-FAK125) is a cytoplasmic tyrosine kinase that plays as an important component in the signal transduction of cell migration, as it modulates cytoskeletal proteins necessary for their movement. UVB-NB radiation induces migration on melanocytes cultures increasing their levels of p-FAK125 and it has been proposed as a melanocyte migration marker.

C-kit is a tyrosine kinase receptor expressed on melanoblasts and differentiated melanocytes. Ligand binding induces PI3K, MAPK and Src kinase pathways, which traduce differentiation of melanoblast into proliferating melanocytes; so its expression imply the presence of mature pigmented melanocytes. C-kit is increased in mature melanocytes after UVB exposure, but it has been show that in melanoma cases the loss of c-kit expression is involved in cancer progression , therefore c-kit signaling is also associated in migratory process. Although, different reports have been established the expression of this markers on vitiligo, is not defined this markers on the repigmentation patterns induces to UVB radiation.

UVB radiation induces repigmentation in distinctive patterns such as follicular, marginal, and diffuse. Follicular pattern is the predominant, and comes from hair follicle melanocytes. In the marginal pattern melanocytes from healthy skin are attracted to the lesion. In the diffuse pattern UVB radiation stimulates those inactive melanocytes. In contrast, achromic pattern not induces melanocyte activation. The relation between the biological behavior of melanocytes and these repigmentation patterns, may provide insights to an improved method to treat vitiligo. The aim of this study is to observe the dynamic of migration and proliferation by specific markers on the repigmentation patterns of vitiligo patients under UVB radiation phototherapy.

Eligibility criteria: Inclusion Criteria:

* Symmetric vitiligo
* Affected body surface greater than 15%
* Patients with follicular, marginal and diffuse repigmenting patterns
* No previous topical or systemic treatment
* Signed informed consent

Exclusion Criteria:

* Concomitant treatment or systemic diseases
* Pregnancy
* Drugs intake
* Mental disorders

Primary outcomes:
measure: Melanocyte phenotype
timeFrame: Up to 1 year
Secondary outcomes:
measure: Melanocyte number
timeFrame: Up to 1 year
measure: Melanogenesis characteristics
timeFrame: Up to 1 year
measure: Melanin presence
timeFrame: Up to 1 year
Other outcomes:
Locations:
Study officials:
affiliation: Universidad Autonoma de San Luis Potosi
name: Diego Cortes-Garcia, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Lepe V, Moncada B, Castanedo-Cazares JP, Torres-Alvarez MB, Ortiz CA, Torres-Rubalcava AB. A double-blind randomized trial of 0.1% tacrolimus vs 0.05% clobetasol for the treatment of childhood vitiligo. Arch Dermatol. 2003 May;139(5):581-5. doi: 10.1001/archderm.139.5.581.
citation: Castanedo-Cazares JP, Lepe V, Moncada B. Repigmentation of chronic vitiligo lesions by following tacrolimus plus ultraviolet-B-narrow-band. Photodermatol Photoimmunol Photomed. 2003 Feb;19(1):35-6. doi: 10.1034/j.1600-0781.2003.00005.x. No abstract available.
citation: Picardo M, Bastonini E. A New View of Vitiligo: Looking at Normal-Appearing Skin. J Invest Dermatol. 2015 Jul;135(7):1713-1714. doi: 10.1038/jid.2015.92.
citation: Wu CS, Lan CC, Yu HS. Narrow-band UVB irradiation stimulates the migration and functional development of vitiligo-IgG antibodies-treated pigment cells. J Eur Acad Dermatol Venereol. 2012 Apr;26(4):456-64. doi: 10.1111/j.1468-3083.2011.04094.x. Epub 2011 May 4.