Clinical Evaluation of Metal Panel Allergens: Mercury, Aluminum and Palladium Dose Response Study

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the diagnostic performance and safety of ascending doses of mercury, aluminum and palladium metal allergens proposed for inclusion in a metal allergen panel. Optimal dose will be selected based on the lowest dose of each allergen eliciting a positive response in 70-90% of subjects tested.

Detailed Description
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This is a single-center, double-blind, randomized study to compare the diagnostic performance (primary) and safety (secondary) of ascending doses of mercury, aluminum and palladium in 20 adult subjects who have a clinical history of contact dermatitis and have had a past positive patch test to one of the allergens on this study. Investigators and subjects will be blinded to the exact location of each dose within the allergen panel but will not be blinded to the allergen being tested, nor the range of allergen doses within each panel.

Official Title
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Clinical Evaluation of Metal Panel Allergens: Mercury, Aluminum and Palladium Dose Response Study

Conditions
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Contact Dermatitis

Intervention / Treatment
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* Diagnostic Test: Ammoniated mercury
* Diagnostic Test: Aluminum chloride and aluminum lactate
* Diagnostic Test: Sodium tetrachloropalladate


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 1.15 years of age or older. 2. History of contact dermatitis. 3. Positive patch results to 1) mercury (elemental), 2) aluminum (aluminum chloride hexahydrate, aluminum hydroxide and/or aluminum lactate) or 3) palladium (sodium tetrachloropalladate and/or palladium chloride) within the past 10 years. 4. Male or non-pregnant non-lactating female. Female subjects must state, at visit one that they are not pregnant, not lactating nor are they intending to become pregnant for the course of the study. 5. Has understood and signed the approved Informed Consent/Assent Form, which is consistent with all institutional, local and national regulations. Assent Form for all minor subjects (ages 15-17) must be signed by the guardian/parent. Exclusion Criteria: Breastfeeding or pregnant or intending to become pregnant for the course of the study. Topical treatment with corticosteroids or other immunosuppressive agents on or near the test area during the 7 days prior to inclusion in this study. Systemic treatment with corticosteroids (equivalent to > 10 mg prednisone) or other immunosuppressive agents during the 7 days prior to inclusion in this study. Inhaled treatments are permitted. Treatment with ultraviolet (UV) light (including tanning) during the 3 weeks prior to inclusion in this study. Acute dermatitis outbreak or dermatitis on or near the test area on the back. Inability to comply with patch test study requirements including multiple return visits and activity restrictions (e.g., protecting test panels from excess moisture due to showering or vigorous activity). Participation in a clinical trial of an investigational drug, treatment or device other than T.R.U.E. TEST during this study or 3 weeks prior to inclusion in this study. An opinion of the Investigator that deems the potential subject to be non-compliant, unable to return for study visits or complete the study as detailed in the protocol.

Ages Eligible for Study
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Minimum Age: 15 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: Diagnostic
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Interventional Model Description: Biologic
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Ammoniated mercury<br>Subjects will be patch tested with 4 experimental doses of ammoniated mercury, 0.013 mg/cm², 0.040 mg/cm², 0.12 mg/cm², and 0.36 mg/cm², a negative control and corresponding reference allergens, 1.0% ammoniated mercury in petrolatum and 0.5% elemental mercury in petrolatum. Patch tests will be worn for 48 hours. | Diagnostic Test: Ammoniated mercury<br>* Metal allergen panel containing ascending doses of ammoniated mercury and a negative control.<br>|
| Experimental: Aluminum chloride and aluminum lactate<br>Subjects will be patch tested with 4 experimental doses of aluminum chloride, 0.040 mg/cm², 0.12 mg/cm², 0.36 mg/cm² and 0.72 mg/cm², 4 experimental doses of aluminum lactate 0.047 mg/cm², 0.14 mg/cm², 0.42 mg/cm² and 0.84 mg/cm², a negative control and corresponding reference allergens, 2.0% aluminum chloride in petrolatum and 12.0% aluminum lactate in petrolatum. Patch tests will be worn for 48 hours. | Diagnostic Test: Aluminum chloride and aluminum lactate<br>* Metal allergen panel containing ascending doses of alumium chloride, aluminum lactate and a negative control.<br>|
| Experimental: Sodium tetrachloropalladaate (Palladium)<br>Subjects will be patch tested with 5 experimental doses of sodium tetrachloropalladate 0.011 mg/cm², 0.033 mg/cm², 0.10 mg/cm², 0.30 mg/cm² and 0.60 mg/cm², a negative control and corresponding reference allergens, 3.0% sodium tetrachloropalladate in petrolatum and 1.0% palladium chloride 1.0% in petrolatum. Patch tests will be worn for 48 hours. | Diagnostic Test: Sodium tetrachloropalladate<br>* Metal allergen panel containing ascending doses of sodium tetrachloropalladate and a negative control.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants Who Exhibit Positive Responses to Each Allergen Concentration | Subjects were patch tested with 4 doses of mercury (0.00mg/cm2-neg control, 0.013 mg/cm2-dose 1, 0.040 mg/cm2-dose 2, 0.12 mg/cm2-dose 3 and 0.36 mg/cm2-dose 4) or 0 doses of aluminum (0.00 mg/cm2-neg control, 0.40 mg/cm2 aluminum chloride-dose 1, 0.12 mg/cm2 aluminum chloride-dose 2, 0.36 mg/cm2 aluminum chloride-dose 3 and 0.72 mg/cm2 aluminum chloride-dose 4, 0.047mg/cm2 aluminum lactate-dose 5, 0.14 mg/cm2 aluminum lactate-dose 6, 0.42 mg/cm2 aluminum lactate-dose 7, 0.84 mg/cm2 aluminum lactate-dose 8) or 5 doses of palladium (0.00 mg/cm2-neg control, 0.011 mg/cm2- dose 1, 0.033 mg/cm2- dose 2, 0.10 mg/cm2- dose 3, 0.30 mg/cm2- dose 4 and 0.60 mg/cm2- dose 5)..Skin reactions were assessed at 3, 4 and 21 days following application. A response is considered positive if it is graded 1+, 2+ or 3+during at least one post removal visit. Overall results are based on Investigator determination following the final study visit. | Patch test sites were evaluated at days 3, 7, 10, 14, and 21 days after application. Results are based on Investigator's review of reactions following the day 21 evaluation | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants Who Exhibit Tape Irritation, Itching and Burning Resulting From Patch Test Panel Application. | Tape irritation is graded on a 4 point scale: None (no tape irritation), Weak (faint to definite pink), Moderate (moderate erythema, definite redness) and Strong (severe erythema, very intense redness). Percentage of response will include weak, moderate and strong reactions. Itching and Burning are graded on a 4 point scale: None (no discomfort), Weak (minimal discomfort), Moderate (definite discomfort) and Strong (significantly bothersome, possible interference with sleep or daily activity). Percentage of response will include weak, moderate and strong responses. | Day 2: 48 hours after application | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Patch Test, Allergy Testing, Contact Dermatitis, Mercury, Aluminum or Palladium skin allergy