Nickel Desensitization Using Topical Therapy

Condition(s) targeted: Allergic Contact Dermatitis

Intervention: Calcipotriol, Betamethasone, Calcipotriol & Betamethasone (Drug)

Phase: N/A

Status: Not yet recruiting

Sponsored by: University of British Columbia

Official(s) and/or principal investigator(s):
Jan P Dutz, MD, Principal Investigator, Affiliation: University of British Columbia

Overall contact:
Gillian de Gannes, MD, Phone: 604-731-5353, Email: gdegannes@gmail.com

Nickel contact dermatitis (eczema) is one of the most common allergic conditions affecting the skin. This is a study looking at potentially desensitizing nickel-allergic patients to their allergy using anti-inflammatory ointments applied to the skin (arm). Application of these ointments (ie. modified Vitamin D) has been shown to increase specific immune cells (T regulatory cells), which play a role in preventing immune activation and subsequently inflammation. The investigators propose use of topical anti-inflammatory agents (corticosteroids, modified Vitamin D, or both) may desensitize patients with nickel allergy.

Official title: Nickel Desensitization Using Topical Therapy

Study design: Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Double Blind (Subject, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Primary outcome: Change in contact dermatitis response to nickel allergen at 5 weeks after topical desensitization

Secondary outcome: Change in immune cell profile of patients 5 weeks after nickel desensitization

Detailed description: 1. Purpose: To evaluate whether topical anti-inflammatory ointments (calcipotriol, betamethasone dipropionate, or a combination of both) can decrease sensitivity to nickel in known nickel allergic patients. Optional blood samples will be part of the protocol to measure immune responses. 2. Hypothesis: Use of these topical agents will prevent sensitization to nickel sulfate upon re-exposure. 3. Justification: Currently, no cure can yet be offered to nickel sensitive patients. Standard treatment only involves avoiding nickel-containing products. However, this is not always easily achieved depending on patient awareness and environmental exposures. Topical desensitization has not yet been explored in patients with pre-established contact allergy. This research will be placebo-controlled with Vaseline petroleum jelly to compare reactions to nickel in those treated with anti-inflammatory ointments. 4. Objectives: a) To evaluate the use of topical anti-inflammatory agents and its role in desensitizing known nickel allergic patients to nickel. b) To measure immune cell responses to nickel allergen from a blood sample taken before and after topical anti-inflammatory application. 5. Research Method: Randomized, double-blinded, placebo-controlled, proof of principle study. Subjects meeting inclusion and exclusion criteria with known nickel sensitivity will be recruited into the study. Those who consent will undergo 3 sets of nickel patch testing: At week 1 to confirm nickel allergic status, week 3 to induce tolerance by patch testing at the site of topical ointment application, and finally at week 5 to test for desensitization. (Week 2 is self-application with topical ointment; Week 4 is a rest week). 6. Statistical Analysis: a) Primary end-point: Clinical responses measured by standard patch testing scores will be documented and photographed for comparison. b) Secondary end-point: Levels of T regulatory cell responses before and after topical treatment. c) Planned sample size: 24 patients. Given that this is a proof-of-principle study, the investigators are choosing to study a small sample size to detect any differences amongst treatment arms, if any. A larger-scale, adequately-powered study would be needed to detect any statistical significance.

Minimum age: 19 Years. Maximum age: N/A. Gender(s): Both.

Criteria:

Inclusion Criteria:

- Age > 18 years.

- Patients have had a diagnosis of nickel allergy determined by patch testing

Exclusion Criteria:

- Treatment with immunomodulating medications concurrently or in the previous one month

- Active skin disease, particularly to the site of application (forearms)

- Hypersensitivity to calcipotriol, corticosteroids, or vehicle

- Previous anaphylactic reactions to nickel allergen

- Pregnancy or breast-feeding

Gillian de Gannes, MD, Phone: 604-731-5353, Email: gdegannes@gmail.com

UBC Contact Dermatitis Clinic, Vancouver, British Columbia V5Z 3Y1, Canada; Not yet recruiting
Gillian de Gannes, MD, Phone: 604-731-5353, Email: gdegannes@gmail.com
Gillian de Gannes, MD, Sub-Investigator

Related publications:

Ghoreishi M, Bach P, Obst J, Komba M, Fleet JC, Dutz JP. Expansion of antigen-specific regulatory T cells with the topical vitamin d analog calcipotriol. J Immunol. 2009 May 15;182(10):6071-8. doi: 10.4049/jimmunol.0804064.

Landeck L, Schalock PC, Baden LA, Neumann K, Gonzalez E. Patch-testing with the standard series at the massachusetts general hospital, 1998 to 2006. Dermatitis. 2009 Mar-Apr;20(2):89-94.

Jacob SE, Moennich JN, McKean BA, Zirwas MJ, Taylor JS. Nickel allergy in the United States: a public health issue in need of a "nickel directive". J Am Acad Dermatol. 2009 Jun;60(6):1067-9. doi: 10.1016/j.jaad.2008.11.893. Epub 2009 Jan 23.

Thyssen JP, Linneberg A, Menné T, Johansen JD. The epidemiology of contact allergy in the general population--prevalence and main findings. Contact Dermatitis. 2007 Nov;57(5):287-99. Review.

Hanneman KK, Scull HM, Cooper KD, Baron ED. Effect of topical vitamin D analogue on in vivo contact sensitization. Arch Dermatol. 2006 Oct;142(10):1332-4.

Moed H, von Blomberg BM, Bruynzeel DP, Scheper RJ, Gibbs S, Rustemeyer T. Regulation of nickel-induced T-cell responsiveness by CD4+CD25+ cells in contact allergic patients and healthy individuals. Contact Dermatitis. 2005 Aug;53(2):71-4.

Wu X, Roelofs-Haarhuis K, Zhang J, Nowak M, Layland L, Jermann E, Gleichmann E. Dose dependence of oral tolerance to nickel. Int Immunol. 2007 Aug;19(8):965-75. Epub 2007 Aug 13.

Cavani A, Nasorri F, Ottaviani C, Sebastiani S, De Pità O, Girolomoni G. Human CD25+ regulatory T cells maintain immune tolerance to nickel in healthy, nonallergic individuals. J Immunol. 2003 Dec 1;171(11):5760-8.

Kang Y, Xu L, Wang B, Chen A, Zheng G. Cutting edge: Immunosuppressant as adjuvant for tolerogenic immunization. J Immunol. 2008 Apr 15;180(8):5172-6.

Zaunders JJ, Munier ML, Seddiki N, Pett S, Ip S, Bailey M, Xu Y, Brown K, Dyer WB, Kim M, de Rose R, Kent SJ, Jiang L, Breit SN, Emery S, Cunningham AL, Cooper DA, Kelleher AD. High levels of human antigen-specific CD4+ T cells in peripheral blood revealed by stimulated coexpression of CD25 and CD134 (OX40). J Immunol. 2009 Aug 15;183(4):2827-36. doi: 10.4049/jimmunol.0803548. Epub 2009 Jul 27.

Starting date: August 2011
Last updated: August 8, 2011