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

Primary Purpose

Skin Inflammation, Allergic Contact Dermatitis

Status

Recruiting

Phase

Phase 2

Locations

United States

Study Type

Interventional

Intervention

Squaric Acid Dibutyl Ester

Known patch test allergens

Dupilumab

Adalimumab

Ustekinumab

Guselkumab

Canakinumab

Sarilumab

Triamcinolone Acetonide

Betamethasone Valerate

Fluticasone Propionate

Microneedle

Suction blistering

Skin punch biopsy

About this trial

This is an interventional basic science trial for Skin Inflammation focused on measuring skin inflammation, allergic contact dermatitis

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesAccepts 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).

Sites / Locations

University of Massachusetts Chan Medical SchoolRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Arm Label

Baseline Contact Allergen

Contact Allergen with Immunomodulator Pre-Treatment

Arm 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.

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.

Outcomes

Primary Outcome Measures

To collect and evaluate single-cell multiomics data (RNAseq, CITEseq, TCRseq)

Baseline and after pre-treatment with immunomodulating medication

Secondary Outcome Measures

Correlation of protein biomarkers collected by microneedles

Correlation to RNA and/or protein expression collected by single-cell multiomics

Full Information

NCT ID

NCT05535738

First Posted

September 6, 2022

Last Updated

May 31, 2023

Sponsor

John Harris

1. Study Identification

Unique Protocol Identification Number

NCT05535738

Brief Title

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

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

May 2023

Overall Recruitment Status

Recruiting

Study Start Date

November 15, 2022 (Actual)

Primary Completion Date

January 1, 2027 (Anticipated)

Study Completion Date

December 31, 2027 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor-Investigator

Name of the Sponsor

John Harris

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

5. Study Description

Brief 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.

Detailed 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Skin Inflammation, Allergic Contact Dermatitis

Keywords

skin inflammation, allergic contact dermatitis

7. Study Design

Primary Purpose

Basic Science

Study Phase

Phase 2, Phase 3

Interventional Study Model

Sequential Assignment

Model Description

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.

Masking

None (Open Label)

Allocation

Non-Randomized

Enrollment

45 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Baseline Contact Allergen

Arm Type

Experimental

Arm Description

Arm Title

Contact Allergen with Immunomodulator Pre-Treatment

Arm Type

Experimental

Arm Description

Intervention Type

Drug

Intervention Name(s)

Squaric Acid Dibutyl Ester

Intervention Description

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%}

Intervention Type

Other

Intervention Name(s)

Known patch test allergens

Intervention Description

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

Intervention Type

Drug

Intervention Name(s)

Dupilumab

Intervention Description

300mg

Intervention Type

Drug

Intervention Name(s)

Adalimumab

Intervention Description

40mg

Intervention Type

Drug

Intervention Name(s)

Ustekinumab

Intervention Description

45mg

Intervention Type

Drug

Intervention Name(s)

Guselkumab

Intervention Description

100mg

Intervention Type

Drug

Intervention Name(s)

Canakinumab

Intervention Description

150mg

Intervention Type

Drug

Intervention Name(s)

Sarilumab

Intervention Description

200mg

Intervention Type

Drug

Intervention Name(s)

Triamcinolone Acetonide

Intervention Description

0.1% ointment

Intervention Type

Drug

Intervention Name(s)

Betamethasone Valerate

Intervention Description

0.1% ointment

Intervention Type

Drug

Intervention Name(s)

Fluticasone Propionate

Intervention Description

0.005% ointment

Intervention Type

Device

Intervention Name(s)

Microneedle

Intervention Description

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

Intervention Type

Device

Intervention Name(s)

Suction blistering

Intervention Description

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.

Intervention Type

Procedure

Intervention Name(s)

Skin punch biopsy

Intervention Description

A skin biopsy is the removal of a small piece of tissue, under local anesthetic.

Primary Outcome Measure Information:

Title

To collect and evaluate single-cell multiomics data (RNAseq, CITEseq, TCRseq)

Description

Baseline and after pre-treatment with immunomodulating medication

Time Frame

Up to 5 years

Secondary Outcome Measure Information:

Title

Correlation of protein biomarkers collected by microneedles

Description

Correlation to RNA and/or protein expression collected by single-cell multiomics

Time Frame

Up to 5 years

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

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).

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Celia Hartigan, RN

Phone

774-455-4758

celia.hartigan@umassmed.edu

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

John Harris, MD, PhD

Organizational Affiliation

University of Massachusetts Chan Medical School

Official's Role

Principal Investigator

Facility Information:

Facility Name

University of Massachusetts Chan Medical School

City

Worcester

State/Province

Massachusetts

ZIP/Postal Code

01605

Country

United States

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Celia Hartigan, RN

Phone

774-455-4758

celia.hartigan@umassmed.edu

First Name & Middle Initial & Last Name & Degree

Elizabeth MacDonald

Phone

774-455-4758

elizabeth.macdonald2@umassmed.edu

First Name & Middle Initial & Last Name & Degree

John Harris, MD, PhD

First Name & Middle Initial & Last Name & Degree

Wei-Che Ko, MD

First Name & Middle Initial & Last Name & Degree

Andressa Akabane, MD

12. IPD Sharing Statement

Learn more about this trial

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

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