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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
Sponsored by
John Harris
About
Eligibility
Locations
Arms
Outcomes
Full info

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

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

First Posted
September 6, 2022
Last Updated
May 31, 2023
Sponsor
John Harris
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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
No
Data Monitoring Committee
No

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
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.
Arm Title
Contact Allergen with Immunomodulator Pre-Treatment
Arm Type
Experimental
Arm 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.
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
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
Email
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
Email
celia.hartigan@umassmed.edu
First Name & Middle Initial & Last Name & Degree
Elizabeth MacDonald
Phone
774-455-4758
Email
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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