Clinical trial NCT03185312: Cutaneous JAK in Vitiligo and Acne Vulgaris.
Official title: Cutaneous JAK Expression in Vitiligo and Acne Vulgaris.
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Vitiligo and Acne Vulgaris
Lead sponsor: Assiut University
Sponsor class: OTHER
First posted: 2017-06-14
Enrollment: 60
Sex: ALL
Minimum age (years): 12
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: CASE_CONTROL
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: A group of 20 patients with vitiligo and 20 patients with acne vulgaris and another control group of 20 age and sex matched healthy volunteers.

Brief summary: The Janus kinase/signal transducer and activator of transcription (JAK-STAT) cytokine signaling pathway is an emerging area of interest in dermatology, and emerging evidence suggests that this pathway may play a crucial role in pathogenesis of inflammatory skin disorders.

Recent advances on the role of cytokines in the pathophysiology of immune mediated inflammatory diseases lead to the understanding that many pro inflammatory interleukins use JAK/STAT components for signal transduction .

Detailed description: The JAK/STAT signaling pathway transmits information from extracellular chemical signals to the nucleus resulting in DNA transcription. Binding of ligands, such as interferon and interleukins, to their specific transmembrane receptors activate associated JAKs. Phosphorylation of STAT follows, and the phosphorylated STAT translocates to the cell nucleus and activates transcription or suppression of target genes .

The JAK family of non-receptor intracellular tyrosine kinases is comprised of four members, JAK1, JAK2, JAK3 and tyrosine kinase (TyK)2. The JAKs are selectively activated by different receptors and have, therefore, distinct in vivo roles. JAK1 is mainly activated by type II cytokine receptors. JAK2 is crucial in transducing signals for cytokine receptors involved in hematopoiesis (erythropoietin, thrombopoietin and haematopoietic cell development cytokines). JAK3 is mainly expressed in B and T lymphocytes, and TYK2 associates commonly with other JAKs.

Cutaneous JAK overexpression has already been demonstrated in a number of inflammatory skin diseases (ISDs) including psoriasis, lichen planus (LP), atopic dermatitis (AD), pyoderma gangrenosum (PG) and alopecia areata (AA); indicating its crucial role in inflammatory keratinocytes.

Furthermore, the recent discovery of the JAK/STAT signaling pathway opened a new window of opportunity for the treatment of ISDs and promoted the development of drugs that block JAK activation.

JAK inhibitors in oral and topical formulations have shown beneficial results in psoriasis and alopecia areata. Patients suffering from vitiligo might also benefit from JAK inhibition. Recently, significant repigmentation was reported in a patient with vitiligo after treatment with tofacitinib, an oral JAK 1/3 inhibitor . However, the knowledge of the cutaneous JAK involvement in vitiligo is scarce. Similarly, little is known about cutaneous JAK expression in acne vulgaris.

Considering the previous findings, there is a need for further elucidation of the JAK signaling in other skin diseases as vitiligo and acne vulgaris.

Eligibility criteria: Inclusion Criteria:

* patients with vitiligo and acne vulgaris.

Exclusion Criteria:

* patients below 12 years of age, or receiving systemic treatments in the last month

Primary outcomes:
measure: To analyze the cutaneous JAK expression in vitiligo and acne vulgaris, assess cutaneous JAK expression in relation to disease severity in vitiligo and acne vulgaris compared to controls
timeFrame: 1 year
Secondary outcomes:
Other outcomes:
Locations:
Study officials:
affiliation: Assiut University
name: Amira Abdel Motaleb, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Palanivel JA, Macbeth AE, Chetty NC, Levell NJ. An insight into JAK-STAT signalling in dermatology. Clin Exp Dermatol. 2014 Jun;39(4):513-8. doi: 10.1111/ced.12273.
citation: O'Shea JJ, Murray PJ. Cytokine signaling modules in inflammatory responses. Immunity. 2008 Apr;28(4):477-87. doi: 10.1016/j.immuni.2008.03.002.
citation: Alves de Medeiros AK, Speeckaert R, Desmet E, Van Gele M, De Schepper S, Lambert J. JAK3 as an Emerging Target for Topical Treatment of Inflammatory Skin Diseases. PLoS One. 2016 Oct 6;11(10):e0164080. doi: 10.1371/journal.pone.0164080. eCollection 2016.
citation: Rawlings JS, Rosler KM, Harrison DA. The JAK/STAT signaling pathway. J Cell Sci. 2004 Mar 15;117(Pt 8):1281-3. doi: 10.1242/jcs.00963. No abstract available.
citation: O'Shea JJ, Schwartz DM, Villarino AV, Gadina M, McInnes IB, Laurence A. The JAK-STAT pathway: impact on human disease and therapeutic intervention. Annu Rev Med. 2015;66:311-28. doi: 10.1146/annurev-med-051113-024537.
citation: Damsky W, King BA. JAK inhibitors in dermatology: The promise of a new drug class. J Am Acad Dermatol. 2017 Apr;76(4):736-744. doi: 10.1016/j.jaad.2016.12.005. Epub 2017 Jan 28.
citation: Papp KA, Menter A, Strober B, Langley RG, Buonanno M, Wolk R, Gupta P, Krishnaswami S, Tan H, Harness JA. Efficacy and safety of tofacitinib, an oral Janus kinase inhibitor, in the treatment of psoriasis: a Phase 2b randomized placebo-controlled dose-ranging study. Br J Dermatol. 2012 Sep;167(3):668-77. doi: 10.1111/j.1365-2133.2012.11168.x.
citation: Ports WC, Khan S, Lan S, Lamba M, Bolduc C, Bissonnette R, Papp K. A randomized phase 2a efficacy and safety trial of the topical Janus kinase inhibitor tofacitinib in the treatment of chronic plaque psoriasis. Br J Dermatol. 2013 Jul;169(1):137-45. doi: 10.1111/bjd.12266.
citation: Craiglow BG, King BA. Tofacitinib Citrate for the Treatment of Vitiligo: A Pathogenesis-Directed Therapy. JAMA Dermatol. 2015 Oct;151(10):1110-2. doi: 10.1001/jamadermatol.2015.1520.
citation: Choi JJ, Park MY, Lee HJ, Yoon DY, Lim Y, Hyun JW, Zouboulis CC, Jin M. TNF-alpha increases lipogenesis via JNK and PI3K/Akt pathways in SZ95 human sebocytes. J Dermatol Sci. 2012 Mar;65(3):179-88. doi: 10.1016/j.jdermsci.2011.11.005. Epub 2011 Nov 20.
citation: Abdel Motaleb AA, Tawfik YM, El-Mokhtar MA, Elkady S, El-Gazzar AF, ElSayed SK, Awad SM. Cutaneous JAK Expression in Vitiligo. J Cutan Med Surg. 2021 Mar-Apr;25(2):157-162. doi: 10.1177/1203475420972340. Epub 2020 Nov 11.