Using a Contact Dermatitis Model With Biologic Medications to Study Skin Inflammation

Wei-Che Ko

Status and phase

Enrolling

Phase 3

Phase 2

Conditions

Skin Inflammation

Allergic Contact Dermatitis

Treatments

Drug: Sarilumab

Drug: Canakinumab

Other: Known patch test allergens

Drug: Adalimumab

Device: Microneedle

Drug: Dupilumab

Drug: Squaric Acid Dibutyl Ester

Drug: Guselkumab

Procedure: Skin punch biopsy

Device: Suction blistering

Drug: Betamethasone Valerate

Drug: Fluticasone Propionate

Drug: Ustekinumab

Drug: Triamcinolone Acetonide

Study type

Interventional

Funder types

Other

Identifiers

NCT05535738

STUDY00000321

Details and patient eligibility

About

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.

Full description

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.

Enrollment

45 estimated patients

Sex

All

Ages

18+ years old

Volunteers

Accepts Healthy Volunteers

Inclusion criteria

Healthy adult subjects over the age of 18 years with no skin diseases
Patients with dermatologic conditions such as atopic dermatitis, history of localized non-melanoma, keratinocytic skin cancer
Patients with previous clinical patch testing
UMass Medical School students and employees are eligible to participate.
Non-English-speaking individuals are also eligible with the assistance of an interpreter and an approved short form consent in the appropriate language.

Exclusion criteria

Adults unable to give consent
History of the following specific dermatologic conditions (which would be confounders due to their particular immunologic etiologies, specifically the TNFa and IL-17 pathways which oppose the Th2 pathway): pityriasis rubra pilaris and psoriasis
Patients actively receiving whole body phototherapy
Patients actively receiving systemic broad-spectrum immunosuppression (prednisone, mycophenolate mofetil, azathioprine, methotrexate)
Any history of poor wound healing
History of uncontrolled diabetes
History of easily torn skin
Any known cardiac arrhythmia or history of heart failure
History of demyelinating disease
History of liver disease or alcohol abuse
History of melanoma
Pregnant women
Individuals who are high risk for tuberculosis including prisoners, immigrants from TB- endemic areas, or US-based travelers who have visited TB-endemic areas
Individuals with a self-reported personal history of infection with latent or active tuberculosis, HIV, Hepatitis B, or Hepatitis C will not be included, because the type of immunotherapies that will be used in this study may interfere with these conditions.
For similar reasons, we will not be including individuals with signs of current or active infection, self-reported personal history of recurrent infections, or conditions that compromise the immune system, such as patients with malignancy (except non- melanoma, keratinocytic skin cancers).

Trial design

Primary purpose

Basic Science

Allocation

Non-Randomized

Interventional model

Sequential Assignment

Masking

None (Open label)

45 participants in 2 patient groups

Baseline Contact Allergen

Experimental group

Description:

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.

Treatment:

Device: Suction blistering

Procedure: Skin punch biopsy

Drug: Squaric Acid Dibutyl Ester

Device: Microneedle

Other: Known patch test allergens

Contact Allergen with Immunomodulator Pre-Treatment

Experimental group

Description:

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.

Treatment:

Drug: Fluticasone Propionate

Drug: Triamcinolone Acetonide

Drug: Ustekinumab

Drug: Betamethasone Valerate

Device: Suction blistering

Procedure: Skin punch biopsy

Drug: Guselkumab

Drug: Squaric Acid Dibutyl Ester

Device: Microneedle

Drug: Dupilumab

Drug: Adalimumab