Immune Signature of Palmoplantar Pustulosis

Palmoplantar Pustulosis Clinical Trial

— PPP  

Official title:

The Immune Signature of Palmoplantar Pustulosis

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01780857
• Other study ID #: 012-275
• Status: Completed
• Phase: N/A
• First received: January 29, 2013
• Last updated: July 9, 2014
• Start date: June 2013
• Est. completion date: July 2014

Study information

• Verified date: July 2014
• Source: Baylor Research Institute
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Observational

Clinical Trial Summary

This study is being done to learn more about a less common "type" of psoriasis, called palmoplantar pustulosis (PPP). The majority of the current treatments used for this type of psoriasis have only a moderate effect on PPP. Thus, the investigators believe that PPP may be a different disease entity altogether, requiring different therapies. As such, the investigators hope to discover an immune signature for this condition.

An immune "signature" is the unique way in which the combination of genes, cells, and proteins of the immune system work for each person. Because both psoriasis and the type of psoriasis patients have been diagnosed with, PPP, are conditions of abnormal immune system function, it is important to understand the overall function of the immune system in this condition (that is, find the immune "signature"). This study should help identify an immune system "signature" in people with PPP.

The investigators have a laboratory technology which allows them to read the genetic "signatures" of a person's blood cells. Genes contain the instructions for making living things. Genes are contained in the cells' DNA (deoxyribonucleic acid). Most DNA is the same among humans, but the small differences people have in their DNA may explain why people develop different diseases. DNA and the genes it contains help produce RNA (ribonucleic acid), which in turn helps make proteins in people's cells. Differences in the types of proteins and the amount of those different proteins people's cells produce can affect a person's immune system.

To help the investigators determine the immune "signature" in PPP, they will be examining the different genes, cells, and proteins that are active in patients with PPP versus patients who do not have the condition. The investigators will examine these genes, cells, and proteins in skin (through a skin sample) and in blood (through a blood draw). The goal is to develop new treatments for this skin condition. To do this, the investigators need to compare the skin and blood of patients with this particular type of psoriasis to the samples of healthy patients.

Description:

I. SPECIFIC AIM

Specific Aim. To identify transcriptional signatures in the skin and blood of patients with palmoplantar pustulosis (PPP).

II. BACKGROUND AND SIGNIFICANCE

Despite major advances in elucidating the molecular pathways of chronic plaque psoriasis (CPP), the immunopathogenesis of PPP, a less common "variant" of psoriasis, remains elusive. It is characterized by the development of inflammatory sterile pustules on the palms and soles of affected individuals, which can be exceptionally painful, interfering with walking and manual activities and impinging significantly on quality of life. Current systemic and biologic treatments used to treat CPP have only a moderate effect in patients with PPP, supporting the suggestion that PPP is a separate disease entity with a distinct immunopathogenic basis. Moreover, the spontaneous paradoxical development of PPP is frequently observed in patients treated with anti-tumor necrosis factor-α therapies, agents typically used in the treatment of CPP. Genetic analysis also distinguishes patients with PPP from those with CPP.

At the investigators' institution, microarray analyses of blood transcriptional patterns have permitted crucial advances in characterizing the immunopathogenesis of immune-mediated conditions such as systemic lupus erythematosis and systemic-onset juvenile idiopathic arthritis. The investigators now wish to examine transcriptional profiles in the skin and blood of patients with PPP to identify the immunopathogenesis of this condition and identify potential therapeutic targets. The investigators will validate the findings at a cellular and protein level using flow cytometry, immunohistochemistry and measuring serum levels of proteins in the blood with Luminex or ELISA.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 30
• Est. completion date: July 2014
• Est. primary completion date: July 2014
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years to 80 Years

Eligibility

Inclusion Criteria:

• Subjects must give written informed consent.

• Subjects are age 18 years or older, with a diagnosis of palmoplantar pustulosis (PPP) or be a healthy control.

• Subjects must be able to adhere to the study visit schedule and other protocol requirements.

• Patient must be off systemic psoriasis therapies (e.g. retinoids, phototherapy, methotrexate, cyclosporine etc.) for at least 4 weeks, biologic therapies for 12 weeks (or 24 weeks in the case of ustekinumab) and off topical therapies (e.g. calcipotriene, topical steroids) for at least 2 weeks.

Exclusion Criteria:

• Inability to provide informed consent.

• Patient is unwilling to be off systemic psoriasis therapies for at least 4 weeks, biologic therapies for 12 weeks (or 24 weeks in the case of ustekinumab) or off topical therapies for at least 2 weeks.

• Unwilling to consent to skin biopsy or blood draw.

• Are pregnant, nursing, or planning a pregnancy while enrolled in the study.

• Uncontrolled medical conditions (diabetes, liver disease, renal disease).

• Have a history of latent or active granulomatous infection, including histoplasmosis or coccidioidomycosis, prior to screening or have had a non-tuberculous mycobacterial infection or opportunistic infection (e.g., cytomegalovirus, pneumocystosis, aspergillosis) within 6 months prior to screening.

Study Design

Observational Model: Cohort, Time Perspective: Prospective

Related Conditions & MeSH terms

• Palmoplantar Pustulosis
• Psoriasis

Locations

Country	Name	City	State
United States	Menter Dermatology Research Institute	Dallas	Texas

Sponsors (3)

Lead Sponsor	Collaborator
Baylor Research Institute	Dermatology Research Institute, Janssen Services, LLC

Country where clinical trial is conducted

United States, 

References & Publications (16)

Allantaz F, Chaussabel D, Stichweh D, Bennett L, Allman W, Mejias A, Ardura M, Chung W, Smith E, Wise C, Palucka K, Ramilo O, Punaro M, Banchereau J, Pascual V. Blood leukocyte microarrays to diagnose systemic onset juvenile idiopathic arthritis and follow the response to IL-1 blockade. J Exp Med. 2007 Sep 3;204(9):2131-44. Epub 2007 Aug 27. Erratum in: J Exp Med. 2009 Sep 28;206(10):2299. Smith, Elisabeth [added]. — View Citation

Asumalahti K, Ameen M, Suomela S, Hagforsen E, Michaëlsson G, Evans J, Munro M, Veal C, Allen M, Leman J, David Burden A, Kirby B, Connolly M, Griffiths CE, Trembath RC, Kere J, Saarialho-Kere U, Barker JN. Genetic analysis of PSORS1 distinguishes guttate psoriasis and palmoplantar pustulosis. J Invest Dermatol. 2003 Apr;120(4):627-32. — View Citation

Bennett L, Palucka AK, Arce E, Cantrell V, Borvak J, Banchereau J, Pascual V. Interferon and granulopoiesis signatures in systemic lupus erythematosus blood. J Exp Med. 2003 Mar 17;197(6):711-23. — View Citation

Berry MP, Graham CM, McNab FW, Xu Z, Bloch SA, Oni T, Wilkinson KA, Banchereau R, Skinner J, Wilkinson RJ, Quinn C, Blankenship D, Dhawan R, Cush JJ, Mejias A, Ramilo O, Kon OM, Pascual V, Banchereau J, Chaussabel D, O'Garra A. An interferon-inducible neutrophil-driven blood transcriptional signature in human tuberculosis. Nature. 2010 Aug 19;466(7309):973-7. doi: 10.1038/nature09247. — View Citation

Chaussabel D, Pascual V, Banchereau J. Assessing the human immune system through blood transcriptomics. BMC Biol. 2010 Jul 1;8:84. doi: 10.1186/1741-7007-8-84. Review. — View Citation

Chaussabel D, Quinn C, Shen J, Patel P, Glaser C, Baldwin N, Stichweh D, Blankenship D, Li L, Munagala I, Bennett L, Allantaz F, Mejias A, Ardura M, Kaizer E, Monnet L, Allman W, Randall H, Johnson D, Lanier A, Punaro M, Wittkowski KM, White P, Fay J, Klintmalm G, Ramilo O, Palucka AK, Banchereau J, Pascual V. A modular analysis framework for blood genomics studies: application to systemic lupus erythematosus. Immunity. 2008 Jul 18;29(1):150-64. doi: 10.1016/j.immuni.2008.05.012. — View Citation

Farley E, Masrour S, McKey J, Menter A. Palmoplantar psoriasis: a phenotypical and clinical review with introduction of a new quality-of-life assessment tool. J Am Acad Dermatol. 2009 Jun;60(6):1024-31. doi: 10.1016/j.jaad.2008.11.910. Review. — View Citation

Griffiths CE, Christophers E, Barker JN, Chalmers RJ, Chimenti S, Krueger GG, Leonardi C, Menter A, Ortonne JP, Fry L. A classification of psoriasis vulgaris according to phenotype. Br J Dermatol. 2007 Feb;156(2):258-62. — View Citation

Ko JM, Gottlieb AB, Kerbleski JF. Induction and exacerbation of psoriasis with TNF-blockade therapy: a review and analysis of 127 cases. J Dermatolog Treat. 2009;20(2):100-8. doi: 10.1080/09546630802441234. Review. — View Citation

Palucka AK, Blanck JP, Bennett L, Pascual V, Banchereau J. Cross-regulation of TNF and IFN-alpha in autoimmune diseases. Proc Natl Acad Sci U S A. 2005 Mar 1;102(9):3372-7. Epub 2005 Feb 22. — View Citation

Pascual V, Allantaz F, Arce E, Punaro M, Banchereau J. Role of interleukin-1 (IL-1) in the pathogenesis of systemic onset juvenile idiopathic arthritis and clinical response to IL-1 blockade. J Exp Med. 2005 May 2;201(9):1479-86. Epub 2005 Apr 25. — View Citation

Pascual V, Allantaz F, Patel P, Palucka AK, Chaussabel D, Banchereau J. How the study of children with rheumatic diseases identified interferon-alpha and interleukin-1 as novel therapeutic targets. Immunol Rev. 2008 Jun;223:39-59. doi: 10.1111/j.1600-065X.2008.00643.x. Review. — View Citation

Pascual V, Chaussabel D, Banchereau J. A genomic approach to human autoimmune diseases. Annu Rev Immunol. 2010;28:535-71. doi: 10.1146/annurev-immunol-030409-101221. Review. — View Citation

Pettey AA, Balkrishnan R, Rapp SR, Fleischer AB, Feldman SR. Patients with palmoplantar psoriasis have more physical disability and discomfort than patients with other forms of psoriasis: implications for clinical practice. J Am Acad Dermatol. 2003 Aug;49(2):271-5. — View Citation

Seneschal J, Milpied B, Vergier B, Lepreux S, Schaeverbeke T, Taïeb A. Cytokine imbalance with increased production of interferon-alpha in psoriasiform eruptions associated with antitumour necrosis factor-alpha treatments. Br J Dermatol. 2009 Nov;161(5):1081-8. doi: 10.1111/j.1365-2133.2009.09329.x. Epub 2009 Jun 5. — View Citation

Wollina U, Hansel G, Koch A, Schönlebe J, Köstler E, Haroske G. Tumor necrosis factor-alpha inhibitor-induced psoriasis or psoriasiform exanthemata: first 120 cases from the literature including a series of six new patients. Am J Clin Dermatol. 2008;9(1):1-14. Review. Erratum in: Am J Clin Dermatol. 2008;9(5):347. — View Citation

* Note: There are 16 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Gene expression profiles	To assess gene expression profiles in the skin and blood of patients with palmoplantar pustulosis compared with those of healthy controls.	2 years	No
Secondary	Examine leukocyte subsets in PPP	To examine leukocyte subsets in the blood of patients with palmoplantar pustulosis compared to healthy controls.	2 years	No