Vitiligo and Acne VulgarisNCT03185312
Cutaneous JAK in Vitiligo and Acne Vulgaris.
An observational study of Vitiligo and Acne Vulgaris, run by Assiut University.
Trial 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. Read more about this study
- Who is it for?
- Ages 12 years and olderHealthy volunteers can take part
- Conditions the study is for
- Vitiligo and Acne Vulgaris
- What is being tested?
- skin biopsy
- How many people
- 60 participants
- Where
- No sites listed yet
- Study dates
- Jan 2018to Jun 2019
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 12 years and older
- All sexes
- Healthy volunteers accepted
- Child, Adult, Older adult
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.
Who may be able to join
- patients with vitiligo and acne vulgaris.
Who cannot join
- patients below 12 years of age, or receiving systemic treatments in the last month
Trial locations and contacts
No sites are listed yet.
About this study
Official title: Cutaneous JAK Expression in Vitiligo and Acne Vulgaris.
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 .
Read the 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.
- Conditions
- Vitiligo and Acne Vulgaris
- Being tested
- skin biopsy
- Medical subject headings
- Vitiligo, Acne Vulgaris
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
skin biopsyDiagnostic test
Clinical evaluation including full history taking and dermatological examination will be done for all patients. Assessment of disease severity will be performed using VASI score for vitiligo and Global acne severity grading for acne vulgaris Skin biopsies will be taken from lesional and non-lesional skin of patients as well as controls. immunohistochemical staining using specific antibodies for detection of expression of JAK1, JAK2 and JAK3.
Additionally, biopsies will be preserved in RNA later solution at -20°C. RNA isolation and real-time qPCR analysis will be performed for measurement of cutaneous JAK1, JAK2 and JAK3 gene expression.
| Study group | Role | What they receive |
|---|---|---|
| patients with acne vulgaris | Clinical evaluation including full history taking and dermatological examination will be done for all patients. Assessment of disease severity will be performed using Global acne severity grading for acne vulgaris Skin biopsies will be taken from lesional and non-lesional skin .immunohistochemical staining using specific antibodies for detection of expression of JAK1, JAK2 and JAK3. Receives: Diagnostic Test: skin biopsy | |
| patients with vitiligo | Clinical evaluation including full history taking and dermatological examination will be done . Assessment of disease severity will be performed using VASI score Skin biopsies will be taken from lesional and non-lesional skin .immunohistochemical staining using specific antibodies for detection of expression of JAK1, JAK2 and JAK3.. Receives: Diagnostic Test: skin biopsy | |
| control | Skin biopsies will be taken from skin of controls.
. Five micron thick sections will be cut from paraffin blocks for immunohistochemical staining using specific antibodies for detection of expression of JAK1, JAK2 and JAK3. Receives: Diagnostic Test: skin biopsy |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Skin biopsies will be taken from lesional and non-lesional skin of patients as well as from healthy volunteers as controls.
All biopsies will be derived from untreated skin lesions for a minimum of 15 days before the biopsy The biopsies will be fixed and paraffin embedded. Five micron thick sections will be cut from paraffin blocks for immunohistochemical staining using specific antibodies for detection of expression of JAK1, JAK2 and JAK3.
Additionally, biopsies will be preserved in RNA later solution at -20°C. RNA isolation and real-time qPCR analysis will be performed for measurement of cutaneous JAK1, JAK2 and JAK3 gene expression.
Measured: 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Jun 2017
- Study startJan 2018 (estimated)
- Primary completionJan 2019 (estimated)
- Study completionJun 2019 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (11)Papers the sponsor has linked to this study.
- Other trials for Vitiligo and Acne VulgarisStudies of the same condition, open and under way.
- More trials run by Assiut UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Case-control
- Time perspective
- Prospective
- Enrolment
- 60 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Assiut University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Yasmin Mostafa Tawfik, Assiut University
- Investigators
- Amira Abdel Motaleb, MD, Principal investigator, Assiut University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03185312
- Sponsor's protocol ID
- CJEIVAA
- Status last verified
- Jun 2017
- First submitted
- 11 Jun 2017
- Last updated
- 14 Jun 2017
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 24825142O'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.
PubMed 18400190Alves 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.
PubMed 27711196Rawlings 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.
PubMed 15020666O'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.
PubMed 25587654Damsky 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.
PubMed 28139263Papp 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.
PubMed 22924949Ports 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.
PubMed 23387374Craiglow 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.
PubMed 26107994Choi 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.
PubMed 22305016Abdel 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.
PubMed 33174479
Study at a glance
From the registry record, last updated by the sponsor on 14 Jun 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Cutaneous JAK Expression in Vitiligo and Acne Vulgaris.
- ClinicalTrials.gov ID
- NCT03185312
- Acronym / sponsor ID
- CJEIVAA
- Conditions
- Vitiligo and Acne Vulgaris
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 60 participants (estimated)
- Lead sponsor
- Assiut UniversityUniversity, hospital or other
- Study start
- Jan 2018 (estimated)
- Primary completion
- Jan 2019 (estimated)
- Study completion
- Jun 2019 (estimated)
- First posted
- 14 Jun 2017 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Observational model
- Case-control
- Time perspective
- Prospective
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| patients with acne vulgaris | – | Diagnostic Test: skin biopsyClinical evaluation including full history taking and dermatological examination will be done for all patients. Assessment of disease severity will be performed using Global acne severity grading for acne vulgaris Skin biopsies will be taken from lesional and non-lesional skin .immunohistochemical staining using specific antibodies for detection of expression of JAK1, JAK2 and JAK3. |
| patients with vitiligo | – | Diagnostic Test: skin biopsyClinical evaluation including full history taking and dermatological examination will be done . Assessment of disease severity will be performed using VASI score Skin biopsies will be taken from lesional and non-lesional skin .immunohistochemical staining using specific antibodies for detection of expression of JAK1, JAK2 and JAK3.. |
| control | – | Diagnostic Test: skin biopsySkin biopsies will be taken from skin of controls. . Five micron thick sections will be cut from paraffin blocks for immunohistochemical staining using specific antibodies for detection of expression of JAK1, JAK2 and JAK3. |
Who may qualify
- Ages
- 12 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child, Adult, Older adult
- 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.
Key inclusion criteria (1 listed)
- patients with vitiligo and acne vulgaris.
Key exclusion criteria (1 listed)
- patients below 12 years of age, or receiving systemic treatments in the last month
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| skin biopsyClinical evaluation including full history taking and dermatological examination will be done for all patients. Assessment of disease severity will be performed using VASI score for vitiligo and Global acne severity grading for acne vulgaris Skin biopsies will be taken from lesional and non-lesional skin of patients as well as controls. immunohistochemical staining using specific antibodies for detection of expression of JAK1, JAK2 and JAK3. Additionally, biopsies will be preserved in RNA later solution at -20°C. RNA isolation and real-time qPCR analysis will be performed for measurement of cutaneous JAK1, JAK2 and JAK3 gene expression. | Diagnostic test | control, patients with acne vulgaris, patients with vitiligo |
Primary outcome
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
Time frame: 1 year
Skin biopsies will be taken from lesional and non-lesional skin of patients as well as from healthy volunteers as controls. All biopsies will be derived from untreated skin lesions for a minimum of 15 days before the biopsy The biopsies will be fixed and paraffin embedded. Five micron thick sections will be cut from paraffin blocks for immunohistochemical staining using specific antibodies for detection of expression of JAK1, JAK2 and JAK3. Additionally, biopsies will be preserved in RNA later solution at -20°C. RNA isolation and real-time qPCR analysis will be performed for measurement of cutaneous JAK1, JAK2 and JAK3 gene expression.
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Jun 2017.
- Background: PubMed 24825142Palanivel 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.
- Background: PubMed 18400190O'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.
- Background: PubMed 27711196Alves 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.
- Background: PubMed 15020666Rawlings 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.
- Background: PubMed 25587654O'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.
- Background: PubMed 28139263Damsky 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.
- Background: PubMed 22924949Papp 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.
- Background: PubMed 23387374Ports 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.
- Background: PubMed 26107994Craiglow 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.
- Background: PubMed 22305016Choi 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.
- Derived from this study: PubMed 33174479Abdel 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.
- Individual participant dataSharing planned: No
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Amira Abdel Motaleb, MD principal investigator
Assiut University
Questions about this trial
What is this clinical trial studying?
An observational study of Vitiligo and Acne Vulgaris, run by Assiut University.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 1 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 14 Jun 2017. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Amira Abdel Motaleb, MD (+201005263721, amiraali21@yahoo.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome 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 (time frame: 1 year). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03185312, which also lists 11 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Jun 2017.