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Reversal of Epidermal Phenotype in Severe Atopic Dermatitis With Cyclosporine Therapy

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01149759
Recruitment Status : Completed
First Posted : June 23, 2010
Results First Posted : March 27, 2017
Last Update Posted : March 27, 2017
Information provided by (Responsible Party):
Mary Sullivan-Whalen, Rockefeller University

Brief Summary:
Atopic Dermatitis (AD) or eczema is a chronic relapsing inflammatory disease that affects 1-3% of the adults and up to 25% of the children in the United States. Patients with severe AD will be studied during a 24-week study with systemic cyclosporine (Neoral, capsule form) to evaluate the immune suppression and pathological correlation of cyclosporine A in these patients in order to determine the extent to which immune activation drives the pathological epidermal phenotype.

Condition or disease Intervention/treatment Phase
Atopic Dermatitis Eczema Drug: Cyclosporine A Not Applicable

Detailed Description:
Patients will be first screened to be sure they are healthy (aside from atopic dermatitis) with a physical exam, and lab tests. These lab tests consist of CBC, biochemical profile, hepatitis B and C profile, urine analysis, HIV, PPD, and urine pregnancy test (if applicable). Patients will return in 2 to 3 days for PPD reading. A repeat serum creatinine will be drawn at this time so as to have 2 baseline values. Patient will begin taking cyclosporine at 5 mg/kg of body weight in 2 divided daily doses for 12 weeks, and after this period the dose will be reduced by 1mg/kg per week (the tapering down will start at 12 weeks of treatment), so that cessation of treatment will occur after 16 weeks from the start of treatment. Patients will then be followed in clinic for an additional 8 weeks for a potential relapse, and if a relapse will occur topical treatment with corticosteroids, immune-modulators or phototherapy may be instituted. Patients will be seen in the outpatient clinic at baseline, wks 1,2, 4, 6, 8, 10, and 12 and every 2weeks until completion of a 24-week study. Biopsies (of lesional and non-lesional skin) will be done to assess histological response at baseline, week 2, week 6 (optional), week 12 and at relapse (optional). Bloods for safety analysis and pregnancy test (if applicable) will be done at each visit, and vital signs will be measured at that time. Serum IgE, eosinophils, and serum cytokines will be done at baseline, and every 2 weeks until week 16, and at week 24. At each visit patients will be assessed for adverse events. Clinical assessment, and ultrasound, will be done at each visit. The most widely accepted clinical assessment tool is known as SCORAD (SCORing for Atopic Dermatitis). This tool combines clinical features of AD such as erythema, dryness, lichenification, percent body surface area, as well as quality of life issues such as pruritus and loss of sleep due to disease. Another assessment tool we will be using is the static IGA (investigator global assessment). The IGA represents an overall evaluation of dermatitis performed by the investigator at every visit. IGA scores utilize a 6-point scale, ranging from 0 (clear) to 5 (very severe disease). IGA scores measure disease severity based on morphology, without referring back to the baseline state. Ultrasound study provides an alternate, non-invasive method of assessing disease activity in the skin. Clinical photos will be done at weeks 0, 6, 12, 16, and 24.In this study, we would like to determine whether AD, like psoriasis, is an immune-driven disease of epidermal hyperplasia and differentiation. To establish the immune contribution to AD, we will treat patients with standard doses of CsA and measure the extent of immune suppression in skin lesions by quantitative measures of pathological leukocytes and expression of inflammatory gene products. At the end of 12 weeks of treatment we will determine whether pathological epidermal hyperplasia is reversed by quantitative and qualitative measures of epidermal hyperplasia and aberrant epidermal differentiation. In addition, we will correlate the extent to which the epidermal phenotype is modulated with the extent to which skin inflammation is suppressed, as the effect of suppression of specific inflammatory molecules on resulting keratinocyte responses is not known. The alternative hypothesis in AD is that it is not an immune-mediated disease, but instead a disease of primary epidermal differentiation due to germline alterations (gene deletions) in filaggrin and other genes that cooperate to differentiate a normal epidermal barrier at the level of stratum corneum. The alternative hypothesis is considered to be the most likely patho-mechanism in AD by a number of current researchers. The alternative hypothesis would be supported by this study if pathologic epidermal hyperplasia persists in the skin regions with significant suppression of the immune/inflammatory pathways induced by CsA treatment.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 9 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Evaluate Reversal of Pathological Epidermal Phenotype in Severe Atopic Dermatitis With Suppression of Immune Activation During Cyclosporine Therapy
Study Start Date : June 2010
Actual Primary Completion Date : December 2014
Actual Study Completion Date : December 2014

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Eczema

Arm Intervention/treatment
Experimental: Cyclosporine A
5 mg/kg for first 4 weeks, followed by tapering to 1 mg/kg for 12 weeks until discontinuation at 16 weeks.
Drug: Cyclosporine A
5 mg/kg for first 4 weeks, followed by tapering to 1 mg/kg for 12 weeks until discontinuation at 16 weeks
Other Name: Neoral

Primary Outcome Measures :
  1. SCORAD Change Score [ Time Frame: 12 weeks ]
    SCORAD ("SCORing Atopic Dermatitis") is a clinical tool for assessing the severity (i.e., extent, intensity) of atopic dermatitis (AD) as objectively as possible with scores ranging from 0-100. The higher the score indicates more severe AD. For this outcome the SCORAD change score is computed as an absolute number which is comparing improvement in the SCORAD score of participants at week 12 compared to their SCORAD score at baseline.

Secondary Outcome Measures :
  1. Change in Epidermal Thickness [ Time Frame: 12 weeks ]
    Change in lesional skin epidermal thickness at week 12 compared to baseline

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Severe AD (defined as having a mean SCORAD score> 40,, with significant disease activity, pruritus, and sleep disturbances (13), suitable for treatment with Cyclosporine, and have failed or unsuitable for other treatment modalities, including topical and or systemic steroids or phototherapy. Patients must also have an IGA score of 3 or greater,
  • Males and females age 18 and above (if females are of child-bearing potential they must agree to use acceptable contraception during the study).
  • No systemic treatment contraception must commence 2 weeks prior to initiating the drug.
  • No systemic treatment for 4 weeks, no topical treatment or phototherapy for 2 weeks

Exclusion Criteria:

  • Previously treated with cyclosporine and had unacceptable toxicity
  • Past or current history of malignancy (except for treated isolated skin cancers)
  • Renal, hepatic, and hematologic laboratory values greater than CTC grade 1 toxicity, such as but not limited to creatinine >1.5 ULN, SGOT>2.5 ULN. Values greater then grade 1 would most likely represent clinically significant renal, hepatic or hematologic disease
  • Stage I hypertension is defined as >140/90. Patients with this blood pressure or higher on two separate occasions, whether on medications or not, will be excluded (JNC guidelines )
  • Significant lipid panel abnormality (any grade 1 toxicity on CTC scale)
  • Lactating females
  • Other medical condition that would increase the risk of cyclosporine toxicity
  • Positive PPD
  • Primary or secondary immune deficiency (including known HIV status)
  • Possible or known pregnancy
  • Serious infection (such as active hepatitis)
  • Drug or alcohol abuse
  • Inability or lack of willingness to co-operate with regular monitoring
  • Severe photodamage/precancerous skin lesions due to previous sunlight exposure, or photo/photochemotherapy
  • Concurrent use of PUVA or UVB, other radiation therapy,
  • Concurrent use of other immunosuppressive agents such as MTX, Immuran, Cyclophosphamide, Cellcept, etc.(because of the possibility of excessive immunosuppression and the subsequent risk of malignancies)
  • Active infections, infections or history of serious infection requiring hospitalization, antibiotics, antivirals,or antifungals within 30 days of baseline
  • History of other inflammatory skin conditions (such as psoriasis, pemphigus, etc.
  • Patients with background skin conditions that might be directly related to atopic dermatitis (such as post inflammatory hyperpigmentation) will not be excluded as well as common background non-inflammatory skin conditions such as seborrheic keratosis, benign pigmented lesions, acne, etc

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01149759

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United States, New York
The Rockefeller University
New York, New York, United States, 10065
Sponsors and Collaborators
Rockefeller University
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Principal Investigator: James Krueger, MD, PhD The Rockefeller University

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Responsible Party: Mary Sullivan-Whalen, Research Nurse Practictioner, Rockefeller University Identifier: NCT01149759     History of Changes
Other Study ID Numbers: JKR-0663
First Posted: June 23, 2010    Key Record Dates
Results First Posted: March 27, 2017
Last Update Posted: March 27, 2017
Last Verified: February 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

Keywords provided by Mary Sullivan-Whalen, Rockefeller University:
Atopic Dermatitis

Additional relevant MeSH terms:
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Dermatitis, Atopic
Skin Diseases
Skin Diseases, Genetic
Genetic Diseases, Inborn
Skin Diseases, Eczematous
Hypersensitivity, Immediate
Immune System Diseases
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antifungal Agents
Anti-Infective Agents
Dermatologic Agents
Antirheumatic Agents
Calcineurin Inhibitors