Effect of Oral Steroids on Skin Outcomes in Atopic Dermatitis (OSAD)

A Double-blind, Placebo-controlled Study to Evaluate the Effects of Oral Steroids on Skin of Patients With Moderate to Severe Atopic Dermatitis Patients

Atopic Dermatitis (AD), also known as eczema, is a common skin disease characterized by itchy lesions. The prevalence of AD has increased over the past few decades, with 15-30% of children and 2-10% of adults being affected. The lesions of atopic dermatitis patients are very inflamed, with an increased number of inflammatory cells in the skin. The first line treatment for AD is steroids, which reduce inflammation in the skin. There are several ways to measure if the treatment is effective, including clinical and cellular. We are proposing that a controlled skin allergen challenge will be an effective way to measure the effect of steroid at a cellular level through the measurement of inflammatory cells in the late cutaneous response. This will be examined using a placebo-controlled trial.

Study Overview

• Status: Terminated
• Conditions: Atopic Dermatitis
• Intervention / Treatment: Drug: Prednisone; Drug: Placebo Control

Detailed Description

This is a double-blind, placebo-controlled, parallel-group clinical trial to evaluate if steroid can block the late cutaneous response after intradermal allergen challenge. Individuals with moderate to severe atopic dermatitis that are develop late cutaneous response to intradermal allergen challenge will be eligible for enrollment. The study is divided into 2 parts.

Part 1: Screening

Subjects who meet all entry criteria will be screened with a medical history and physical examination. If they continue to meet entry criteria, their atopic status will be documented by skin testing against common airborne allergens (including cat, dust mite, grass, pollen) and an intradermal allergen challenge will be performed with a select allergen extract. Only subjects with a documented late cutaneous response to intradermal allergen challenge will be eligible for entry into Part 2 of the study.

Part 2: Dosing and Follow-up

Subjects will be randomly assigned 1:1 to receive either prednisone or placebo treatment. Prednisone treatment will be 5 days of 0.75 mg/kg, 5 days of 0.5 mg/kg and 5 days of 0.25 mg/kg. Before dosing and on Day 9 of dosing an intradermal allergen challenge will be performed and a skin biopsy of the late cutaneous response will be evaluated 24 hours after each intradermal allergen challenge. A sample of blood and skin from a lesion will be obtained before and on Day 9 of treatment. Patients will return for a follow up visit on Day 16 for safety.

• Study Type: Interventional
• Enrollment (Actual): 16
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Hamilton, Ontario, Canada, L8N 3Z5
      • McMaster University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Male and female volunteers 18 through 65 years of age.
• Females must not be pregnant
• General good health
• Moderate to severe atopic dermatitis
• Able to understand and give written informed consent and sign a written informed consent form approved by the HIREB (Hamilton Integrated Research Ethics Board)
• Positive skin-prick test to common allergens (including cat, dust mite, grass, pollen)
• Positive late cutaneous response to intradermal allergen challenge

Exclusion Criteria:

• Treatment with an investigational drug within 8 weeks or within 5 half-lives (if known), whichever is longer, before the baseline visit
• Having used any of the following treatments within 4 weeks before the baseline visit, or any condition that, in the opinion of the investigator, is likely to require such treatment(s) during the first 4 weeks of study treatment:
• Immunosuppressive/immunomodulating drugs (eg, systemic corticosteroids, cyclosporine, mycophenolate-mofetil, Interferon-γ (IFN-γ), Janus kinase inhibitors, azathioprine, methotrexate, etc.)
• Phototherapy for AD
• Treatment with biologics as follows:
• Any cell-depleting agents including but not limited to rituximab: within 6 months before the baseline visit, or until lymphocyte count returns to normal, whichever is longer
• Other biologics: within 5 half-lives (if known) or 16 weeks prior to baseline visit, whichever is longer
• Initiation of treatment of AD with prescription moisturizers or moisturizers containing additives such as ceramide, hyaluronic acid, urea, or filaggrin degradation products during the screening period (patients may continue using stable doses of such moisturizers if initiated before the screening visit)
• Regular use (more than 2 visits per week) of a tanning booth/parlor within 4 weeks of the baseline visit
• Active chronic or acute infection requiring treatment with systemic antibiotics, antivirals, antiparasitics, antiprotozoals, or antifungals within 2 weeks before the baseline visit, or superficial skin infections within 1 week before the baseline visit. Note: patients may be rescreened after infection resolves
• Known or suspected history of immunosuppression, including history of invasive opportunistic infections (eg, tuberculosis [TB], histoplasmosis, listeriosis, coccidioidomycosis, pneumocystosis, aspergillosis) despite infection resolution: or unusually frequent, recurrent, or prolonged infections, per investigator judgment
• History of human immunodeficiency virus (HIV) infection
• History of hepatitis B or hepatitis C infection
• Presence of skin comorbidities that may interfere with study assessments
• Severe concomitant illness(es) that, in the investigator's judgment, would adversely affect the patient's participation in the study
• Any other medical or psychological condition that may make patient's participation unreliable, or may interfere with study assessments.
• Planned or anticipated major surgical procedure during the patient's participation in this study
• Patient is a member of the investigational team or his/her immediate family
• Pregnant women

Study Plan

How is the study designed?

Design Details

• Primary Purpose: BASIC_SCIENCE
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: QUADRUPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Prednisone Treatment; Prednisone will be administered orally for 15 days at the following doses: 0.75 mg/kg of body weight for 5 days 0.5 mg/kg of body weight for 5 days 0.25 mg/kg of body weight for 5 days	Drug: Prednisone; Total treatment duration: 15 days Doses are as follows: 5 days daily treatment with 0.75 mg/kg of body weight 5 days daily treatment with 0.5 mg/kg of body weight 5 days daily treatment with 0.25 mg/kg of body weight
Placebo Comparator: Placebo Control; Placebo will be administered orally for 15 days in a capsule identical to the experimental treatment.	Drug: Placebo Control; Total treatment duration: 15 days. Doses will appear identical to prednisone arm.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Late Cutaneous Response (LCR)	Measured by size of the wheal.	Measured 24 hours after intradermal allergen challenge on day 2 and day 9 of study.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Comparison of eosinophils and basophils in the LCR between drug and placebo using histopathology.	The eosinophils and basophils will be measured by histopathology on the LCR biopsy.	Biopsy of LCR taken 24 hours after intradermal allergen challenge on day 2 and day 9 of study.
Comparison of eosinophils and basophils in the LCR between drug and placebo using flow cytometry.	The eosinophils and basophils will be measured by flow cytometry on the LCR biopsy.	Biopsy of LCR taken 24 hours after intradermal allergen challenge on day 2 and day 9 of study.

Collaborators and Investigators

• Sponsor: McMaster University

Study record dates

Study Major Dates

• Study Start (Actual): January 24, 2017
• Primary Completion (Actual): August 8, 2018
• Study Completion (Actual): August 8, 2018

Study Registration Dates

• First Submitted: September 8, 2016
• First Submitted That Met QC Criteria: September 16, 2016
• First Posted (Estimate): September 21, 2016

Study Record Updates

• Last Update Posted (Actual): August 20, 2018
• Last Update Submitted That Met QC Criteria: August 16, 2018
• Last Verified: August 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Skin Diseases; Immune System Diseases; Hypersensitivity, Immediate; Genetic Diseases, Inborn; Skin Diseases, Genetic; Hypersensitivity; Skin Diseases, Eczematous; Dermatitis; Eczema; Dermatitis, Atopic; Physiological Effects of Drugs; Anti-Inflammatory Agents; Antineoplastic Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Prednisone
• Other Study ID Numbers: McMaster-OSAD

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: We plan to tabulate and include IPD in publication in medical journal.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No