- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT05535738
Using a Contact Dermatitis Model With Biologic Medications to Study Skin Inflammation
Biologics and Blistering - Using a Contact Dermatitis Model With Biologic Medications to Study Skin Inflammation Through Suction Blistering
Study Overview
Status
Conditions
Intervention / Treatment
- Drug: Squaric Acid Dibutyl Ester
- Other: Known patch test allergens
- Device: Microneedle
- Device: Suction blistering
- Drug: Dupilumab
- Drug: Adalimumab
- Drug: Ustekinumab
- Drug: Guselkumab
- Drug: Canakinumab
- Drug: Sarilumab
- Drug: Triamcinolone Acetonide
- Drug: Betamethasone Valerate
- Drug: Fluticasone Propionate
- Procedure: Skin punch biopsy
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.
Study Type
Enrollment (Estimated)
Phase
- Phase 2
- Phase 3
Contacts and Locations
Study Contact
- Name: Celia Hartigan, RN
- Phone Number: 774-455-4758
- Email: celia.hartigan@umassmed.edu
Study Locations
-
-
Massachusetts
-
Worcester, Massachusetts, United States, 01605
- Recruiting
- University of Massachusetts Chan Medical School
-
Contact:
- Celia Hartigan, RN
- Phone Number: 774-455-4758
- Email: celia.hartigan@umassmed.edu
-
Contact:
- Elizabeth MacDonald
- Phone Number: 774-455-4758
- Email: elizabeth.macdonald2@umassmed.edu
-
Principal Investigator:
- John Harris, MD, PhD
-
Sub-Investigator:
- Wei-Che Ko, MD
-
Sub-Investigator:
- Andressa Akabane, MD
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
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).
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Basic Science
- Allocation: Non-Randomized
- Interventional Model: Sequential Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Baseline Contact Allergen
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.
|
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%}
Positive patch test allergens during the course of clinical patch testing will be re-applied on the back followed by skin sampling
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 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.
A skin biopsy is the removal of a small piece of tissue, under local anesthetic.
|
Experimental: Contact Allergen with Immunomodulator Pre-Treatment
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.
|
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%}
Positive patch test allergens during the course of clinical patch testing will be re-applied on the back followed by skin sampling
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 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.
300mg
40mg
45mg
100mg
150mg
200mg
0.1% ointment
0.1% ointment
0.005% ointment
A skin biopsy is the removal of a small piece of tissue, under local anesthetic.
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
To collect and evaluate single-cell multiomics data (RNAseq, CITEseq, TCRseq)
Time Frame: Up to 5 years
|
Baseline and after pre-treatment with immunomodulating medication
|
Up to 5 years
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Correlation of protein biomarkers collected by microneedles
Time Frame: Up to 5 years
|
Correlation to RNA and/or protein expression collected by single-cell multiomics
|
Up to 5 years
|
Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: John Harris, MD, PhD, University of Massachusetts Chan Medical School
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Estimated)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Estimated)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Pathologic Processes
- Skin Diseases
- Immune System Diseases
- Hypersensitivity
- Skin Diseases, Eczematous
- Hypersensitivity, Delayed
- Inflammation
- Dermatitis
- Dermatitis, Contact
- Dermatitis, Allergic Contact
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Autonomic Agents
- Peripheral Nervous System Agents
- Enzyme Inhibitors
- Anti-Inflammatory Agents
- Antirheumatic Agents
- Immunosuppressive Agents
- Immunologic Factors
- Glucocorticoids
- Hormones
- Hormones, Hormone Substitutes, and Hormone Antagonists
- Dermatologic Agents
- Adjuvants, Immunologic
- Bronchodilator Agents
- Anti-Asthmatic Agents
- Respiratory System Agents
- Anti-Allergic Agents
- Tumor Necrosis Factor Inhibitors
- Adalimumab
- Betamethasone
- Betamethasone Valerate
- Betamethasone-17,21-dipropionate
- Betamethasone benzoate
- Betamethasone sodium phosphate
- Triamcinolone
- Fluticasone
- Xhance
- Triamcinolone Acetonide
- Triamcinolone hexacetonide
- Triamcinolone diacetate
- Ustekinumab
- Squaric acid dibutyl ester
Other Study ID Numbers
- STUDY00000321
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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