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

Allergic Contact Dermatitis Clinical Trial

Official title:

Biologics and Blistering - Using a Contact Dermatitis Model With Biologic Medications to Study Skin Inflammation Through Suction Blistering

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05535738
• Other study ID #: STUDY00000321
• Status: Recruiting
• Phase: Phase 2/Phase 3
• Start date: November 15, 2022
• Est. completion date: December 31, 2027

Study information

• Verified date: May 2023
• Source: University of Massachusetts, Worcester
• Contact: Celia Hartigan, RN
• Phone: 774-455-4758
• Email: celia.hartigan[@]umassmed.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 45
• Est. completion date: December 31, 2027
• Est. primary completion date: January 1, 2027
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years and older

Eligibility

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).

Related Conditions & MeSH terms

• Allergic Contact Dermatitis
• Dermatitis
• Dermatitis, Allergic Contact
• Dermatitis, Contact
• Inflammation
• Skin Inflammation

Intervention

Drug:
• Squaric Acid Dibutyl Ester
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%}

Other:
• Known patch test allergens
Positive patch test allergens during the course of clinical patch testing will be re-applied on the back followed by skin sampling

Drug:
• Dupilumab
300mg
• Adalimumab
40mg
• Ustekinumab
45mg
• Guselkumab
100mg
• Canakinumab
150mg
• Sarilumab
200mg
• Triamcinolone Acetonide
0.1% ointment
• Betamethasone Valerate
0.1% ointment
• Fluticasone Propionate
0.005% ointment

Device:
• Microneedle
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
• Suction blistering
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.

Procedure:
• Skin punch biopsy
A skin biopsy is the removal of a small piece of tissue, under local anesthetic.

Locations

Country	Name	City	State
United States	University of Massachusetts Chan Medical School	Worcester	Massachusetts

Sponsors (1)

Lead Sponsor	Collaborator
John Harris

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	To collect and evaluate single-cell multiomics data (RNAseq, CITEseq, TCRseq)	Baseline and after pre-treatment with immunomodulating medication	Up to 5 years
Secondary	Correlation of protein biomarkers collected by microneedles	Correlation to RNA and/or protein expression collected by single-cell multiomics	Up to 5 years