Nickel Desensitization Using Topical Therapy

Study Overview
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Brief Summary
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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
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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.

Official Title
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Nickel Desensitization Using Topical Therapy

Conditions
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Allergic Contact Dermatitis

Intervention / Treatment
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* Drug: Calcipotriol, Betamethasone, Calcipotriol & Betamethasone


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 19 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Calcipotriol ointment<br> | Drug: Calcipotriol, Betamethasone, Calcipotriol & Betamethasone<br>* 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.<br>* Other names: Betamethasone diproprionate (0.5% ointment USP generic);|
| Active Comparator: Betamethasone dipropionate ointment<br> | Drug: Calcipotriol, Betamethasone, Calcipotriol & Betamethasone<br>* 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.<br>* Other names: Betamethasone diproprionate (0.5% ointment USP generic);|
| Active Comparator: Calcipotriol and betamethasone ointment<br> | Drug: Calcipotriol, Betamethasone, Calcipotriol & Betamethasone<br>* 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.<br>* Other names: Betamethasone diproprionate (0.5% ointment USP generic);|
| Placebo Comparator: Vaseline Petroleum Jelly<br> | Drug: Calcipotriol, Betamethasone, Calcipotriol & Betamethasone<br>* 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.<br>* Other names: Betamethasone diproprionate (0.5% ointment USP generic);|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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). | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Allergic contact dermatitis, Nickel allergy, Desensitization therapy