Nickel Desensitization Using Topical Therapy
Primary Purpose
Allergic Contact Dermatitis
Status
Unknown status
Phase
Not Applicable
Locations
Canada
Study Type
Interventional
Intervention
Calcipotriol, Betamethasone, Calcipotriol & Betamethasone
Sponsored by
About this trial
This is an interventional treatment trial for Allergic Contact Dermatitis focused on measuring Allergic contact dermatitis, Nickel allergy, Desensitization therapy
Eligibility 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
Sites / Locations
- UBC Contact Dermatitis Clinic
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm Type
Active Comparator
Active Comparator
Active Comparator
Placebo Comparator
Arm Label
Calcipotriol ointment
Betamethasone dipropionate ointment
Calcipotriol and betamethasone ointment
Vaseline Petroleum Jelly
Arm Description
Outcomes
Primary Outcome Measures
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
Secondary Outcome Measures
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.
Full Information
NCT ID
NCT01413477
First Posted
April 13, 2011
Last Updated
August 8, 2011
Sponsor
University of British Columbia
1. Study Identification
Unique Protocol Identification Number
NCT01413477
Brief Title
Nickel Desensitization Using Topical Therapy
Official Title
Nickel Desensitization Using Topical Therapy
Study Type
Interventional
2. Study Status
Record Verification Date
August 2011
Overall Recruitment Status
Unknown status
Study Start Date
August 2011 (undefined)
Primary Completion Date
February 2012 (Anticipated)
Study Completion Date
June 2012 (Anticipated)
3. Sponsor/Collaborators
Name of the Sponsor
University of British Columbia
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief 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.
Detailed Description
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.
Hypothesis: Use of these topical agents will prevent sensitization to nickel sulfate upon re-exposure.
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.
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.
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).
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Allergic Contact Dermatitis
Keywords
Allergic contact dermatitis, Nickel allergy, Desensitization therapy
7. Study Design
Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Single Group Assignment
Masking
ParticipantInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
24 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Calcipotriol ointment
Arm Type
Active Comparator
Arm Title
Betamethasone dipropionate ointment
Arm Type
Active Comparator
Arm Title
Calcipotriol and betamethasone ointment
Arm Type
Active Comparator
Arm Title
Vaseline Petroleum Jelly
Arm Type
Placebo Comparator
Intervention Type
Drug
Intervention Name(s)
Calcipotriol, Betamethasone, Calcipotriol & Betamethasone
Other Intervention Name(s)
Dovonex (calcipotriol ointment, DIN 01976133 Leo Pharma),, Dovobet (DIN 02244126, Leo Pharma), Betamethasone diproprionate (0.5% ointment USP generic)
Intervention Description
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.
Primary Outcome Measure Information:
Title
Change in contact dermatitis response to nickel allergen at 5 weeks after topical desensitization
Description
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
Time Frame
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.
Secondary Outcome Measure Information:
Title
Change in immune cell profile of patients 5 weeks after nickel desensitization
Description
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.
Time Frame
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).
10. Eligibility
Sex
All
Minimum Age & Unit of Time
19 Years
Accepts Healthy Volunteers
No
Eligibility 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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Gillian de Gannes, MD
Phone
604-731-5353
Email
gdegannes@gmail.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jan P Dutz, MD
Organizational Affiliation
University of British Columbia
Official's Role
Principal Investigator
Facility Information:
Facility Name
UBC Contact Dermatitis Clinic
City
Vancouver
State/Province
British Columbia
ZIP/Postal Code
V5Z 3Y1
Country
Canada
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Gillian de Gannes, MD
Phone
604-731-5353
Email
gdegannes@gmail.com
First Name & Middle Initial & Last Name & Degree
Gillian de Gannes, MD
12. IPD Sharing Statement
Citations:
PubMed Identifier
19414758
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.
Results Reference
background
PubMed Identifier
19426614
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.
Results Reference
background
PubMed Identifier
19167779
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. No abstract available.
Results Reference
background
PubMed Identifier
17937743
Citation
Thyssen JP, Linneberg A, Menne T, Johansen JD. The epidemiology of contact allergy in the general population--prevalence and main findings. Contact Dermatitis. 2007 Nov;57(5):287-99. doi: 10.1111/j.1600-0536.2007.01220.x.
Results Reference
background
PubMed Identifier
17043189
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. doi: 10.1001/archderm.142.10.1332.
Results Reference
background
PubMed Identifier
16033398
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. doi: 10.1111/j.0105-1873.2005.00635.x.
Results Reference
background
PubMed Identifier
17698564
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. doi: 10.1093/intimm/dxm066. Epub 2007 Aug 13.
Results Reference
background
PubMed Identifier
14634084
Citation
Cavani A, Nasorri F, Ottaviani C, Sebastiani S, De Pita 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. doi: 10.4049/jimmunol.171.11.5760.
Results Reference
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PubMed Identifier
18390698
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. doi: 10.4049/jimmunol.180.8.5172.
Results Reference
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PubMed Identifier
19635903
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.
Results Reference
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Nickel Desensitization Using Topical Therapy
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