Evaluation of Pyroptosis-related Indicators in the Pathogenesis of Vitiligo:Across-sectional Comparative Study

Vitiligo Clinical Trial

Official title:

Evaluation of Pyroptosis-related Indicators in the Pathogenesis of Vitiligo:Across-sectional Comparative Study

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06261086
• Other study ID #: soh-med-24-01-06MS
• Status: Not yet recruiting
• Phase: N/A
• Start date: February 24, 2024
• Est. completion date: August 24, 2024

Study information

• Verified date: February 2024
• Source: Sohag University
• Contact: marwa A Mohammed, resident
• Phone: 01009160620
• Email: marwa.mohamed5[@]med.sohag.edu.eg
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Vitiligo is an acquired pigmentary disorder on skin and/or mucosae, which is characterized by death of melanocytes (MCs), affecting 0.5%-2% of the population worldwide (1). It doesn't affect the health of patients but it has marked social pressure and greatly interfere with their quality of life (2,3). It presents with well circumscribed milky white patches that occur secondary to destruction of melanocyte, it may appear at any age and affect both sexes equally.

It can affect ethnic groups and people of all skin types with no predilection (4).

Clinically, several types of vitiligo are distinguished according to the distribution of the achromic lesions. One or more lesions in a dermatomal pattern are characteristic for segmental vitiligo (SV) while this segmental distribution is absent in non-segmental vitiligo (NSV). The latter variety includes both the focal type and the generalized type (5). Numerous previous studies tried to illustrate the pathogenesis behind the disease, but the exact pathophysiology is still not fully understood. It is a multifactorial disease. Factors include, neural theory, oxidative stress theory, autoimmune hypothesis, intrinsic theory, melanocytorrhagy hypothesis (6). Many theories tried to explain the mechanisms of MC destruction in vitiligo. Apoptosis is one of the most widely studied cell death pathways. In addition, the other two forms of cell death, conventional necrosis and autophagy seem to be involved in the death of vitiligo MCs under certain situations. Moreover, new types of regulated cell death including necroptosis, pyroptosis, and ferroptosis may also participate in the pathogenesis (7). Pyroptosis is a highly inflammatory form of necrosis cell death NCD regulated mainly by caspase-1, which is initiated following large supramolecular complex ermed inflammasome activation (8). The inflammasome-activated Caspases then cleave the pyroptosis-inducing protein Gasdermin D (GSDMD), which forms a pore in the plasma membrane and causes cell lysis as well as the secretion of IL-1β typically (9). Another study suggests that inflammasome activation could be a useful marker for assessing disease progression of vitiligo (10). However, the link between vitiligo and inflammasome activation is still unclear. The inflammasome regulates cell death and inflammation via activation of caspase-1 (11). The activation of caspase-1 promotes the secretion of proinflammatory cytokines IL-1β and IL-18, as well as the initiation of pyroptosis (12). So, evaluation of pyroptosis-related indicators (GASDM-D, IL 1β & IL-18) may help understanding the obscure inflammasome pathway involvement in the pathogenesis of Vitiligo.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 90
• Est. completion date: August 24, 2024
• Est. primary completion date: August 24, 2024
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Patients with vitiligo = 18 years old, both male and female patients will be included.

Exclusion Criteria:

• Patients with the following criteria will be excluded from our study:

1. Pregnancy and breast-feeding women

2. patients on antioxidants or anti-inflammatory drugs

3. Patients on topical/systemic treatment for vitiligo in the last 4weeks prior to enrollment in the study

4. Patients with other dermatological diseases as psoriasis, lichen planus, viral infection, etc.

5. Patients suffering from chronic medical illness such as; diabetes mellitus, thyroid disease, and cancer.

Related Conditions & MeSH terms

• Vitiligo

Intervention

Diagnostic Test:
• evaluate serum levels pyroptosis-related indicators (GASDM-D, IL 1ß & IL-18)
2 ml blood will be collected from all participants (patients and controls) by aseptic venipuncture into plain tubes. Then the samples will be allowed to coagulate during 10-20 minutes. Serum will be obtained by centrifugation at speed of 2000-3000 cycle/min for 20 minutes. Then we collect the supernatant which immediately be frozen at -80°C until analyzed to determine serum levels of pyroptosis-related indicators (GASDM-D, IL 1ß & IL-18). Serum concentration will be assessed by a commercially available double antibody sandwich enzyme-linked immunosorbent assay (ELISA) kit

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Sohag University

References & Publications (4)

Alikhan A, Felsten LM, Daly M, Petronic-Rosic V. Vitiligo: a comprehensive overview Part I. Introduction, epidemiology, quality of life, diagnosis, differential diagnosis, associations, histopathology, etiology, and work-up. J Am Acad Dermatol. 2011 Sep;65(3):473-491. doi: 10.1016/j.jaad.2010.11.061. — View Citation

Kruger C, Schallreuter KU. A review of the worldwide prevalence of vitiligo in children/adolescents and adults. Int J Dermatol. 2012 Oct;51(10):1206-12. doi: 10.1111/j.1365-4632.2011.05377.x. Epub 2012 Mar 27. — View Citation

Osinubi O, Grainge MJ, Hong L, Ahmed A, Batchelor JM, Grindlay D, Thompson AR, Ratib S. The prevalence of psychological comorbidity in people with vitiligo: a systematic review and meta-analysis. Br J Dermatol. 2018 Apr;178(4):863-878. doi: 10.1111/bjd.16049. Epub 2018 Feb 7. — View Citation

Salman A, Kurt E, Topcuoglu V, Demircay Z. Social Anxiety and Quality of Life in Vitiligo and Acne Patients with Facial Involvement: A Cross-Sectional Controlled Study. Am J Clin Dermatol. 2016 Jun;17(3):305-11. doi: 10.1007/s40257-016-0172-x. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	GASDM-D	Evaluartion of serum level of (GASDM-D) in patients with Vitiligo as well as in control health group. 2- To correlate level of GASDM-D with severity of the disease.	6 months
Primary	IL 1ß	Evaluation of serum level of IL 1ß in patients with Vitiligo as well as in control health group 2- To correlate level of IL 1ß with severity of the disease.	6 months
Primary	IL-18	Evaluation of serum level of IL-18 in patients with Vitiligo as well as in control health group 2- To correlate level of IL-18 with severity of the disease.	6 months