Nickel Desensitization Using Topical Therapy

Allergic Contact Dermatitis Clinical Trial

Official title:

Nickel Desensitization Using Topical Therapy

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT01413477
• Other study ID #: H10-02854
• Status: Not yet recruiting
• Phase: N/A
• First received: April 13, 2011
• Last updated: August 8, 2011
• Start date: August 2011
• Est. completion date: June 2012

Study information

• Verified date: August 2011
• Source: University of British Columbia
• Contact: Gillian de Gannes, MD
• Phone: 604-731-5353
• Email: gdegannes[@]gmail.com
• Is FDA regulated: No
• Health authority: Canada: Health Canada
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 24
• Est. completion date: June 2012
• Est. primary completion date: February 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 19 Years and older

Eligibility

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

Study Design

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

Related Conditions & MeSH terms

• Allergic Contact Dermatitis
• Dermatitis
• Dermatitis, Allergic Contact
• Dermatitis, Contact

Intervention

Drug:
• Calcipotriol, Betamethasone, Calcipotriol & Betamethasone
All study patients will be randomized to receive one of four topical ointments (calcipotriol, betamethasone dipropionate, combination of both calcipotriol/betamethasone dipropionate, or Vaseline petroleum jelly). Each subject will receive one unlabelled 5g tube for application to be dispensed by pharmacist, Rudy Chin. We expect approximately 2g of TOTAL use (0.125g applied twice daily over a 5 cm x 5 cm area on one forearm for 7 days). Typically, topical steroids such as betamethasone dipropionate have been used for treating a number of inflammatory skin conditions, including eczema. In addition, vitamin D analogues such as calcipotriol are used to treat psoriasis. Both agents, in our study, will be used on a small area of normal skin for a short 7 day course.

Locations

Country	Name	City	State
Canada	UBC Contact Dermatitis Clinic	Vancouver	British Columbia

Sponsors (1)

Lead Sponsor	Collaborator
University of British Columbia

Country where clinical trial is conducted

Canada, 

References & Publications (10)

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in contact dermatitis response to nickel allergen at 5 weeks after topical desensitization	Erythema, induration, blistering of the skin will be noted. The standardized Likert scale (0-3+) will be used as follows: + Weak (non-vesicular) reaction: erythema, infiltration, possibly papules; ++ Strong (edematous or vesicular) reaction; +++ Extreme (spreading, bullous or ulcerative) reaction; Negative reaction	All study subjects will be evaluated after each patch test session (weeks 1, 3, 5). The final outcome to assess for desensitization will be evaluated at week 5.	No
Secondary	Change in immune cell profile of patients 5 weeks after nickel desensitization	Peripheral T cells will be separated and responses will be determined by flow cytometry after nickel desensitization therapy. Approximately 50 ml of blood will be drawn from consenting subjects. Absolute cell numbers and immunophenotypes of cells will be reported.	All consenting subjects will have baseline blood drawn at week 0 and again at week 5 to compare any differences in immune cells (ie. T cells).	No