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The purpose of this study is to answer: how do inflammation and anti-inflammatory skin therapies work in the skin? Inflammation is a protective response from the body's immune system to injury, disease, or irritation. It is a process by which your body's white blood cells and the things they make protect you from infection from outside invaders such as bacteria and viruses.
The purpose of this study is to study mechanisms of human skin inflammation by using an established model of transient contact dermatitis with pre-treatment by biologic drugs that block specific inflammatory signals or by topical steroids that block broad inflammatory signals. Contact dermatitis will be induced in a safe and controlled manner through the use of topical application of squaric acid dibutyl ester (SADBE), along with other common allergens, after which skin will be sampled for analysis using nonscarring skin biopsy techniques including suction blister biopsies and/or application of absorptive microneedle patches.
This IRB protocol will use select FDA-approved, commercially available biologic drugs and topical steroids that have good safety profiles and block inflammatory signals that we observed in our previously acquired data of contact dermatitis.
This study will provide insight into human immunology that will deepen our understanding of dermatologic disease, as well as increase our understanding of topical steroids and biologic treatments which sometimes cause paradoxical inflammation despite being designed to suppress inflammation. We hope this will improve the basic understanding of human skin inflammation in order to ultimately impact treatment strategies for several skin diseases.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Baseline Contact Allergen | Experimental | Individuals who will have allergic contact dermatitis induced via squaric acid dibutyl ester (SADBE) and/or known patch test allergens followed by skin and blood sampling. There is a protocol to sensitize individuals to SADBE if they have not previously been exposed to SADBE. |
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| Contact Allergen with Immunomodulator Pre-Treatment | Experimental | Individuals from Arm 1 (Baseline Contact Allergen) who have been exposed to SADBE and/or known patch test allergens followed by skin and blood sampling. These individuals will be pre-treated via administration of a single dose of 1 biologic from the following list: dupilumab, adalimumab, ustekinumab, guselkumab, canakinumab, sarilumab; or a single application of 1 topical steroid from the following list: betamethasone valerate, triamcinolone acetonide, fluticasone propionate. Allergic contact dermatitis will then be induced and the skin sampled. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Squaric Acid Dibutyl Ester | Drug | Sensitization dose: 2% Elicitation doses: {0.0001%, 0.00025%, 0.00075%, 0.001%, 0.0025%, 0.005%, 0.0075%, 0.01%, 0.025%, 0.05%, 0.06%, 0.07%, 0.08%, 0.09%, 0.1%, 0.2%, 0.3%, 0.4%, 0.5%, 0.6% 0.7%, 0.8%, 0.9%, 1.0%, 1.2%, 1.4%, 1.6%, 1.8%, 2.0%} |
| Measure | Description | Time Frame |
|---|---|---|
| To collect and evaluate single-cell multiomics data (RNAseq, CITEseq, TCRseq) | Baseline and after pre-treatment with immunomodulating medication | Up to 5 years |
| Measure | Description | Time Frame |
|---|---|---|
| Correlation of protein biomarkers collected by microneedles | Correlation to RNA and/or protein expression collected by single-cell multiomics | Up to 5 years |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Wei-Che Ko, MD | University of Massachusetts, Worcester | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of Massachusetts Chan Medical School | Worcester | Massachusetts | 01605 | United States |
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There are two phases in this study. The first phase involves sensitization to a contact allergen and skin sampling to establish baseline characteristics. In the second phase, the participant will be pre-treated with a one time dose of an immunomodulating medication, re-treated with a contact allergen, followed by skin sampling.
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| Known patch test allergens | Other | Positive patch test allergens during the course of clinical patch testing will be re-applied on the back followed by skin sampling |
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| Dupilumab | Drug | 300mg |
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| Adalimumab | Drug | 40mg |
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| Ustekinumab | Drug | 45mg |
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| Guselkumab | Drug | 100mg |
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| Canakinumab | Drug | 150mg |
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| Sarilumab | Drug | 200mg |
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| Triamcinolone Acetonide | Drug | 0.1% ointment |
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| Betamethasone Valerate | Drug | 0.1% ointment |
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| Fluticasone Propionate | Drug | 0.005% ointment |
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| Microneedle | Device | Painless and non-scarring skin sampling with a 7mm x 7mm patch of hydrogel-coated poly-l-lactide microneedles (<2mm length) will be used to collect interstitial fluid |
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| Suction blistering | Device | Suction blistering is a technique to induce and collect blister fluid using a negative pressure instrument (Electronic Diversities Finksburg, MD). It does not require local anesthetic, stitches or pain medication following the procedure. The blisters will be no greater than 1cm in diameter and no deeper than the epidermis (<1mm deep). This process of inducing blisters is typically less than 1 hour. After the formation of blisters, the blister fluid will be extracted using a syringe. The blister roofs will be left attached to the skin and covered with petrolatum and a bandage. |
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| Skin punch biopsy | Procedure | A skin biopsy is the removal of a small piece of tissue, under local anesthetic. |
|
| ID | Term |
|---|---|
| D003872 | Dermatitis |
| D017449 | Dermatitis, Allergic Contact |
| ID | Term |
|---|---|
| D012871 | Skin Diseases |
| D017437 | Skin and Connective Tissue Diseases |
| D003877 | Dermatitis, Contact |
| D017443 | Skin Diseases, Eczematous |
| D006968 | Hypersensitivity, Delayed |
| D006967 | Hypersensitivity |
| D007154 | Immune System Diseases |
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| ID | Term |
|---|---|
| C020637 | squaric acid dibutyl ester |
| C582203 | dupilumab |
| D000068879 | Adalimumab |
| D000069549 | Ustekinumab |
| C000588857 | guselkumab |
| C541220 | canakinumab |
| C000592401 | sarilumab |
| D014222 | Triamcinolone Acetonide |
| D001624 | Betamethasone Valerate |
| D000068298 | Fluticasone |
| ID | Term |
|---|---|
| D061067 | Antibodies, Monoclonal, Humanized |
| D000911 | Antibodies, Monoclonal |
| D000906 | Antibodies |
| D007136 | Immunoglobulins |
| D007162 | Immunoproteins |
| D001798 | Blood Proteins |
| D011506 | Proteins |
| D000602 | Amino Acids, Peptides, and Proteins |
| D012712 | Serum Globulins |
| D005916 | Globulins |
| D014221 | Triamcinolone |
| D011245 | Pregnadienes |
| D011278 | Pregnanes |
| D013256 | Steroids |
| D000072473 | Fused-Ring Compounds |
| D011083 | Polycyclic Compounds |
| D013259 | Steroids, Fluorinated |
| D001623 | Betamethasone |
| D011246 | Pregnadienetriols |
| D000730 | Androstadienes |
| D000736 | Androstenes |
| D000731 | Androstanes |
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